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Arterial Hypertension in Young Adults: An Ignored Chronic Problem

Author: Manuela   Stoicescu, MD, PhD

Original research

Manuela   Stoicescu, MD, PhD

Consultant Internal Medicine, Assistant Professor

Faculty of Medicine and Pharmacy, Medical Disciplines Department

University of Oradea,  Romania

 

ABSTRACT

Introduction:

Don’t ignore the young patients: being young does not necessary mean being healthy.

Objectives:

The objectives in this study was to analyzed the principal clinical aspects and conduct laboratory investigations with young people in group of age 18-35 years. Attracting attention to the diagnosis of hypertension in the young in the early stages of life. I choice this topic because high blood pressure in the young, in particularly, in this group age was insufficiently studied while a high frequency of cases presented every day was continuously  increasing.

Material and method:

The study was performed in the Ambulatory Specialty of the Internal Diseases Department in the County Hospital in Oradea, Romania. Study period was  1 October 2006 to 31 July 2009. Included in the study were 321 patients with hypertension exceeding 140/90 mmHg which was maintained higher after three consecutive determinations in intervals of one week to exclude the “white coat phenomenon”, an effect noted very frequent in young people, especially in young women, because a young persons have hyperactivity of simpatico nervous systemic, or the value of blood pressure was higher more than 170/110 mmHg from first determination.

Results

1. Importance of the genetic factors in the etiologies of disease was suggests that family prevalence of hypertension in the young people and another family diseases like hyperaldosteronism, polycystic kidney and multiple endocrine neoplasias MEN2a.

2. Importance of personal pathologic antecedents demonstrated in my study that repetitive Streptococcus angina with Streptococcus β hemolytic group A originated in the first place as a cause in hypertension in the young people in context of acute streptococcal renal parenchymatous diseases.

3. Renin plasmatic level is a very important marker of high blood pressure in the young. It was high in 121 cases (37.69%). This situation suggests that hypertension in the young is hyperreninemic hypertension in many cases because a young person has a systemic hyperactivity of simpatico nervous.

4. Left ventricular hypertrophy is been detected in X-ray, ECG and echocardiography. In my studied I detected left ventricular hypertrophy in 35 patients representing 10.49%.

5. Proteinuria was represented in 96 cases (29.90%) has two meanings:

  • nephropathy complication of hypertension  or
  • acute glomerulonephritis or
  • nephritis syndrome accompaniment with hematuria 38 cases (11.83%).

6. The eye ground findings of young people with hypertension are frequently normal. In the absence of prior readings, one needs to look for evidence of target organ damage that may suggest chronicity. In my study this changes appeared for 86 cases 23.3 %, hemorrhages and exudates I rarely found in 9 cases represent 2.8% and papilla edema was presented in 2 cases even when hypertension was very severe more than 200/120 mmHg and complicate with hypertensive encephalopathy.

Conclusions: Guidelines for hypertension treatment with young patients group of ages 18-35 was developed, which I hope will help the activity of physicians in general specialties in their practice, to use for diagnosis and easy work. This is new and hypertension in the young in this group of ages was insufficiently studied.

Key words: hypertension diagnosis, young adults.


INTRODUCTION

Prior to the last twenty years it was impossible to accept the idea that hypertension and atherosclerosis begin in adolescence and even earlier in childhood. Current concepts concerning the nature of hypertension in the young are changing. Earlier clinical impressions indicated that hypertension in the young was secondary and the essential hypertension occurred only rarely.

In my recent study, involving young people, of the age group of age 18-35 year old, indicated that young with high levels of blood pressure often the cause is known and often is unknown. When high BP (HBP) is found in the young the young compared with their peers, it is  likely that the HBP will continue to Adulthood. My study has indicated that the level of blood pressure in young is closely related to the occurrence of hypertension in adulthood. Thus, changing concepts suggest that essential hypertension begins in early life. Considerable information is now known about the clinical and pathologic features of hypertension in adults.

We understand clinical diagnoses, the pathophysiology and humoral background, and the consequences of end stage renal disease (ESRD). We are even beginning to consider that essential hypertension may represent more than one disease. By contrast, little is known about the early natural development of essential hypertension. For example, how can hypertension in young be defined? We cannot equate level of blood pressure with cardiovascular damage as in adults (cardiovascular, cerebral, and renal disease). Furthermore, there is little specific information that can be used to predict development of adult hypertension. As a beginning, descriptive studies of the early natural development of essential hypertension are needed. It is logical to assume that prevention would be most successful if the disease process could be understood and treated in its earliest phase.

OBJECTIVES

      Don’t ignore the young adult patient. Being young does not necessary means being healthy. Key objectives in my study was to analyze the principal clinical aspects and laboratory tests performed on  young adults in the group age 18-35 year old, to advocate for the attention needed for diagnosis of hypertension in the young adults in the early stages of the disease.                                                                                                         

MATERIAL AND METHOD

     The study was performed in the Ambulatory Specialty of the Internal Diseases Department at the County Hospital in Oradea, Romana. Study period was  1 October 2006 to 31 July 2009. Study participants:

  • 321 young patients,
  • group of ages 18-35, patients with high blood pressure more than 140/90 mmHg
  • after three consecutive determinations in interval one week maintain higher than 140/90 mmHg to exclude the “white coat phenomenon”, effect very frequently encountered with young adults especially with young women, because young person have a hyperactivity of sympathetic nervous system, or
  • the value of blood pressure was high more than 170/110mmHg from first determination.

The patients had a comprehensive physical examination (clinical and par clinical) and diagnosed with hypertension in different stages.

The study consideration was done after having confirmed the diagnosis of hypertension and the standardization according to the phenomenon of high blood pressure and the classification of OMS.

The patients agreed to participate after being introduced in the study after they have been explained the deontological and preserving of the confidentiality criteria.

For statistics data I has been used the EPIINFO application, 6.0 version, a program of The Center of Disease Control and Prevention- Atlanta, with the Student method (test t) and χ²

RESULTS AND DISCUSSIONS

We observed that a 1/5 of the patients studied have in family antecedents of young adults hypertensive member of the family:hypertension in 70 cases (21.80%), stroke in 46 cases  (14.33%), myocardial infarction in 55 cases (17.13%), peripheral vascular disease in 23 cases ( 7.16%)  obesity 38 (11.83%), pre-eclamptic toxemia in 31 cases(9.65% ), hyperaldosteronism in 18 cases (5.60%),  polycystic kidney in 26 cases (8.09%), multiple endocrine neoplasias MEN2a in 14 cases (4.36%) Distribution of cases according to family history.  See, Table 1.

Table 1: Distribution of Cases according to Family History

Consideration

No. of cases

Percent

Hypertension for parents, grandparents, aunts, uncles and cousins

70

21.80%

Family antecedents of stroke

46

14.33 %

Family antecedents of myocardial infarction

55

17.13%

Family antecedents of peripheral vascular disease

23

7.16%

Family antecedents of obesity

38

11.83%

Pre-eclamptic toxemia

31

9.65%

Hyperaldosteronism

18

5.60%

Polycystic kidney

26

8.09%

Multiple endocrine neoplasias MEN2a

14

4.36%

A significant numbers of patients in my studies did not have any  antecedents of hypertension in their family history. That fact demonstrates that not only genetic factors have an important role in the etiology of the disease.ENvironmental factors count.

Significant number of  hypertensive young  patients had diseases in their personal history: Scarlatti in 27 (8.41%), repetitive angina with Streptococcus β hemolytic group A in 88 (27.41%), chronic ORAL infection focus in 35 (10.90%) chronic stomathological focus infections in 19 (5.91%), nephritis in 34(10.59%), endocrine disorders in 16 (4.98% ), physical and psychological in 22 (6.85%), head trauma in 11 (3.42%), therapy with corticosteroids secondary to another disease (for example erythematous systemic lupus) in 5 (1.55%),  therapy with AINS  drugs in 21 (6.54%), use decongestion nasal in 4 (1.24%) repetitive urinary tract infection in 28 (8.72%), syphilis in 11 (3.42%). See, Table II.

Table II: Distribution of Cases by Illnesses in  Personal History

Consideration

No. of cases

Percent

Scarlatti

27

8.41%

Repetitive Streptococcus angina with Streptococcus β hemolytic group A

88

27.41%

Chronic ORAL infection focus

35

10.90%

Chronic stomathological infection focus

19

5.91%

Nephritis

34

10.59%

Endocrine disorders

16

4.98%

Physical and psychical suprademanding

22

6,85%

Head  trauma

11

3,42%

Therapy with corticosteroids

5

1.55%

Therapy with AINS

21

6.54%

Use decongestion at nasal

4

1.24%

Repetitive urinary tract infections

28

8.72%

Syphilis

11

3.42%

Fig.1: Principal Diseases Etiology for Young Hypertensive Patients

HY1

Table III: Laboratory Results

Hemoglobin value ↑

18

5.60%

Hematocrit ↑

18

5.60%

Value of glucose ↑

68

21.18%

Cholesterol  ↑

78

24.29%

HDL cholesterol  ↑

86

26.79%

LDL cholesterol  ↑

77

23.67%

Triglycerides ↑

105

32.71%

Uric acid  ↑

57

17.75%

Creatinina ↑

38

11.83%

Urea ↑

36

11.21%

Serum sodium ↑

42

13.08%

Serum potassium↓

42

13.08%

Urinalysis -albuminuria+

-hematuria+

96

29.90%

38

11.83%

Urine culture with female +

104

32.29%

Table IV: Laboratory Special Tests

Rennin plasmatic↑

121

37.69%

Vanillyl Mandelic Acid testing (VMA): in urine↑

18

5.60%

Catecholamine urine↑

18

5.60%

Cortisol urine ↑

9

2.80%

Cortisolemia  ↑

9

2.80%

TSH ↑

16

4.98%

T3    ↑

16

4.98%

T4   ↑

16

4.98%

CT abdominal

114

35.51%

RMN abdominal

158

49.92%

Intravenous urogrography

102

31.77%

Observations on Eye Exam and Retinopathy [The eye ground (eye ground findings)]

Clearly, the most helpful information to have when one is attempting to establish the chronicity of hypertension is past blood pressure readings. Unfortunately, these are by no means always available since routine blood pressure measurement in young adults is not yet uniformly obtained. In the absence of prior readings, one needs to look for evidence of target organ damage that may suggest chronicity. In adolescent with even severe chronic hypertension or hypertensive encephalopathy. In my study this changes appear for the optic fund may show no more than retinal arteriolar narrowing in 103 cases represent 32.09% and arterio-venous nicking in 98 cases represent 30.53%, hemorrhages and exudates I rarely found in 9 cases represent 2.8%, papilla edema may be absent except in 2 cases even when hypertension was very severe more than 200/120 mmHg with complications of encephalopathy and in 109 cases represent 33.96 was normal result of eye ground examination. See Table V and Fig. 2

Just as there may be minimal eye ground findings, there are infrequently cardiac findings that suggest chronicity.

Table V  Distribution of Cases by Eye Exam Findings

Normal

109

33.96%

Arteriolar narrowing

103

32.09%

Arterio-venous nicking

98

30.53%

Exudates and hemorrhages

9

2.80%

Papilla edema

2

0.62%

HY2

Fig. 2: Distribution of Cases by Changes of Eye Ground Findings

The heart morphology was not clinically enlarged in many cases and the ECG and chest X-ray were usually unhelpful in detecting left ventricular hypertrophy unless hypertension has been prolonged and severe. In my studies left ventricular hypertrophy was present in 35 cases (10.49%), they are helpful in determining chronicity of hypertension and in 206 cases (64.18%) left ventricular hypertrophy was absent.  If negative suggesting nothing about the duration of hypertension. See Table VI and Fig 3

Table VI: Distribution of Cases by Changes in Chest X-Ray

Normal

206

64.18%

Elongation and elevated of left inferior arcos

99

30.85%

Cardiomegaly

12

3.73%

Aneurism of thoracic aorta

4

1.24%

HY3

Fig. 3: Distribution of Cases by Changes of chest X-Ray

The echocardiography seems to be more sensitive for evaluating chamber size and wall thickness than the ECG and can be helpful. Left atria hypertrophy and left ventricular hypertrophy (Sokolow -Lyon index) and left axial deviation was possible to detect. In my studies I found 35 cases (10.49%) with LVH, 36 cases (11.21%) with LAH and 35 cases (10.49%) with left axial deviation. Secondary changes of depolarization like ST segment sub elevated and negative T wave I found in 35 cases represent 10.49%. See Table VII and Fig. 4

Table 7: Distribution of Cases by Changes in ECG

Normal

180

56.07%

Left axial deviation> -30

35

10.90%

Left atria hypertrophy

36

11.21%

Left  ventricular hypertrophy

Sokolov -Lyon index(SV1+RV5/V6>35mm)

35

10.90%

Secondary  changes of depolarization – ST segment sub elevated  and T wave negative

35

10.90%

HY4

Fig. 4: Distribution of Cases by Changes in ECG

Table VIII:  Distribution of cases by Echocardiography of Hearth Examination

Normal

226

70.40%

Left ventricular hypertrophy

40

12.46%

Ejection fraction(FE) of left ventricular<55%

27

8.41%

Aortic coarctation

28

8.72%

HY5

Fig. 5: Distribution of cases by Changes in Echocardiography

Table IX: Distribution of Cases by Urine Analysis Results

Normal

187

58.27%

Proteinuria

96

29.90%

Hematuria

38

11.83 %

Proteinuria I detect in 96 cases (29.90%) and hematuria in 38 cases (11.83%). See Fig. 6

HY6

Fig.6: Distribution of cases by Urine Analysis Results

OMS stadialization classification high blood pressure in three stages. In my study about hypertension in the young adults,  the results are as follows:

  • Stages I:  270 cases represents 84.11%,
  • Stages II:  40 cases represents 12.46%,
  • Stages III:  9 cases (2.80%) and
  • Stage IV: malign hypertension 2 cases represents 0.62%.

See, Table IX  and Fig.7

Table IX: Distribution of Cases by Stadialization

Stages I

270

84.11%

Stages II

40

12.46%

Stages III

9

2.81%

Stages IV

2

0.62%

                                                              

HY7

Fig. 7: Distribution of Cases by Stadialization

DISCUSSION

1.   A 1/5 of group of patients studied have in family antecedents of young hypertensive family member with the following diseases:

  • stroke 46 cases  (14.33%),
  • myocardial infarction 55 cases (17.13%),
  • peripheral vascular disease 23 cases (7.16%),
  • obesity 38 (11.83%),
  • pre-eclamptic toxemia 31 cases (9.65%),
  • hiperaldosteronism in 18 cases (5.60%),
  • polycystic kidney 26cases (8.09%),
  • multiple endocrine diseases II 14 cases (4.36%).

These results  are in concordance with observations of Kotchen JM [1] which in a studies about young hypertensive patients concluded that family aggregation of hypertension was very frequent 20.2% (p<0,001) suggesting the importance of a genetic factor in the etiology of hypertension in the young adults.

    2.   An important number of  hypertensive young  patients were present in personal pathological antecedents: Scarlatti 27 (8.41%), repetitive angina with Streptococcus β hemolytic group A 88 (27.41%),chronic ORL infection focus 35 (10.90%) chronic stomathological focus infections 19 (5.91%), nephritis 34 (10.59%), endocrine disorders 16 (4.98% ), physical and psychical supra solicitation 22 (6.85%), head trauma 11 ( 3.42% ), therapy with corticosteroizi  from another disease (for example erithematous systemic lupus) 5 (1.55%) therapy with AINS  drugs 21 (6.54%), use decongestion nasal 4 (1.24%) repetitive urinary tract infection 28 (8.72%), syphilis 11 (3.42%)(p<0,001). Loggie JMH [2] in a studies with  hypertension in the young reported the streptococcus infection with Streptococcus β hemolytic group A was 18.2% , chronic ORAL infection focus was 8.9%, chronic stomathological focus infections was 3.98%, glomerulonephritis was 6.2% and  physical and psychical supra solicitation was 12.43% in personal pathological antecedents.

3.   Changes of retinal vascular were insufficiently studied in young adults. In my study this changes appear for the optic fund may show no more than retinal arteriolar narrowing 103 cases represent 32.09% and arterio venous nicking 98 cases represent 30.53% , hemorrhages and exudates I rarely found from 9 cases represent 2.8%, papilla edema may be absent except 2 cases even with hypertension was very severe more than 200/120mmHg and complicate with encephalopathy and 109 cases represent 33.96% was normal result of funduoscopic examination (p<0.001).

Skalina MEL et al. [3] observations: 281 hypertensive young patients 140 have changes for the optic fund arterio venous nicking 93 cases, hemorrhages found from 7 cases and exudates appear from 40 patients. 141 patients have the optic fund examination normal.

4.   The heart is not often clinically enlarged and the ECG and chest X-ray are usually unhelpful in detecting left ventricular hypertrophy unless hypertension has been prolonged and severe. In my studies left ventricular hypertrophy was present in 35 cases (10.49%), they are helpful in determining chronicity of hypertension and from 206 cases (64.174%) left ventricular hypertrophy was absent, that suggest that if negative, they tell one nothing about the duration of hypertension. The results are in concordance with observation with Laird WP and Fixler DE [4] who reports after performing chest X-ray for 210 young hypertensive, 103 have normal results, 78 have elongation and elevated of left inferior arcos and 29 present’s cardiomegaly.

5.   The echocardiogram seems to be more sensitive for evaluating chamber size and wall thickness than the ECG and can be helpful. Left atria hypertrophy and left ventricular hypertrophy (Sokolow-Lyon index) and left axial deviation it’s possible to detect. In my studies I found 35 cases (10.49%) with LVH, 36 cases (11.21%) with LAH and 35 cases (10.49%) with left axial deviation. Secondary changes of depolarization like ST segment sub elevated and negative T wave I found from 35 cases represent 10.49% (p<0,001).The results are in concordance with observation with Laird WP and Fixler DE [4], who reports than 18% from young hypertensive subject, presents left ventricular hypertrophy detected after echocardiography examination, end in concordance with observation with Schieken RM et al. [5] in Muscatine studies who reports more than 14% from young hypertensive subjects have left ventricular hypertrophy after make echocardiography examination.

6.   Proteinuria I detect in 96 cases (29.90%) and hematuria in 38 cases (11.83%).This changes appear in context of acute  glomerulonephritis and hypertension was secondary renal.

Schmider et al. [6] sustained that glomerular hyperfiltration is a early marker for nefroangiosclerosis and a sign for subclinical organ affected.

7. OMS stadialization classification high blood pressure in three stages. In my study about hypertension in young adults the results are: in stages I found 270 cases represents 84.11%, in stages II 40 cases represents 12.46%, in stages III 9 cases (2.80%) and malign hypertension 2 cases represents 0.62%.

CONCLUSIONS

  • 1. Importance of genetic factors in etiologies of disease is suggested that family aggregation of hypertension in young adults and another familial diseases like hyperaldosteronism, polycystic kidney and multiple endocrine diseases II.
  • 2. Importance of personal pathologic antecedents demonstrated in my study that repetitive Streptococcus angina with Streptococcus β hemolytic group A was found in the first place as a cause of hypertension in the young people in context of acute streptococcal renal parenchymatous diseases.
  • 3. Except nonspecific symptoms of high blood pressure exist specifically symptoms who suggest etiology of hypertension with young people.
  • 4. The fundoscopic findings in the young adult with hypertension are frequently normal. In the absence of prior readings, one needs to look for evidence of target organ damage that may suggest chronicity. In my study this changes appear for 86 cases 23.3 %  and hemorrhages and exudates I rarely found from 9 cases represent 2.8% and papilla edema may be absent except 2 cases even with hypertension is very severe more than 200/120mmHg and complication of encephalopathy.
  • 5. Left ventricular hypertrophy is possible to detect X-ray, ECG and echocardiography. In my studied I detected left ventricular hypertrophy from 35 patients represent 10.49%.
  • 6. Proteinuria 96 cases (29.90%) have two significance:  nephropathy complication of high blood pressure, or etiology in context or glomerulonephritis alone or accompaniment with hematuria 38 cases (11.83%) in nephritis syndrome.
  • 7. Renin plasmatic level is very important marker of high blood pressure in the young. Was high in 121 cases (37.69%).This situation suggests that hypertension in the young is hiperreninemic hypertension in many cases because young adults have hyperactivity of sympatetic nervous system.
  • 8. OMS classification evaluated stages I 270 cases (84.11%), stages II 40 cases (12.46%) in stages III 9 cases (2.80%) and malign hypertension (stages IV) 2 cases (0.62%)
  • 9. Finally I make a small guideline about hypertension with young patients group of ages 18-35, which I hope to help activity of every physician indifferent specialties in your practice, to use for diagnosis and easy work.

REFERENCES

1. Kotchen JM “Effect of relative weight on familial blood pressure aggregations“ Am J Epidemiol.1987 105-214.

2. Loggie JMH. “The diagnostic evaluation of adolescents with hypertension.” In Hunt JC, Dreifus LS, Dustan HP et al, eds Dialogues in Hypertension Update II vol 1. Lyndhurst, NJ: Health Learning Systems 1984:43-56.

3. Skalina MEL et al.:  Annable WL, Kleigman RM, Fanaroff AA “ Hypertensive retinopathy in the adolescent“ J Adolesc. 1983:103:781-6.

4. Laird WP and Fixler DE. “Left ventricular hypertrophy in adolescents with elevated blood pressure: assessment by chest roentgenography, electrocardiography and echocardiography.” Adolescents 2001;67:255-9.

5.Schieken RM and coauthors: Clarke WR, Lauer RM, “Left ventricular hypertrophy in the young with blood pressures in the upper quin-tile of the distribution: the Muscatine study.” Hypertenesion 2004;3:669-75.

6. Schmider and coauthors: Messerli FH, Garavaglia GE, Nunez BD “Glomerular hyperfiltration indicates target organ disease in essential hypertension.” Circulation 2003; 76: III-273.

 

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Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 5/29, 2013

Renal Denervation Safe in Real-World Setting

By Todd Neale, Senior Staff Writer, MedPage Today

Published: May 25, 2013

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points:

PARIS — May 21-24, 2013

Out in everyday practice, renal denervation with the Symplicity device safely lowers blood pressure in patients with hypertension, preliminary results from the Global SYMPLICITY registry showed.

The Global SYMPLICITY registry is part of the clinical program evaluating the Symplicity device. It has been approved for use in Europe and elsewhere but remains restricted to investigational use in the U.S. Medtronic, which makes the Symplicity device, announced on Thursday that it has completed enrollment in Symplicity HTN-3, the pivotal U.S. trial.

The registry has a targeted enrollment of about 5,000 patients from about 200 centers worldwide; 149 sites spread throughout Canada, Mexico, South America, Europe, Africa, the Middle East, Asia, and Australia have already started collecting data.

Any patient who receives renal denervation can be included in the registry, and thus the study will include patients with hypertension and other conditions associated with increased sympathetic activity, including heart failure, insulin resistance, atrial fibrillation, sleep apnea, and chronic kidney disease.

European Society of Cardiology‘s recently published consensus paper on renal denervation, which recommended treatment in patients with a systolic blood pressure of 160 mm Hg or higher (or at least 150 mm Hg for type 2 diabetics) who were taking at least three antihypertensive medications, including a diuretic.

SOURCE:

Expert consensus document from the European Society of Cardiology on catheter-based renal denervation

http://eurheartj.oxfordjournals.org/content/early/2013/04/25/eurheartj.eht154.extract

Most of the first 617 patients included the registry (60%) were treated in accordance with the European Society of Cardiology’s recently published consensus paper on renal denervation, above.

About one-fifth of the patients (22%) started with a systolic blood pressure of at least 180 mm Hg, which was the average baseline blood pressure in the Symplicity HTN-1 and HTN-2 trials.

The average starting blood pressure overall was 164/89 mm Hg, and patients were taking an average of 4.35 medications. Common comorbidities included diabetes (38.2%), renal disease (30.1%), sleep apnea (16.3%), a history of cardiac disease (49%), heart failure (9.3%), and atrial fibrillation (11.9%).

The registry data showed significant drops in blood pressure measured both in the office and with 24-hour ambulatory monitoring, although the reductions were smaller than those seen in the clinical trials.

That’s not surprising, according to Mahfoud, because out in everyday practice blood pressure is not recorded as appropriately as in a clinical trial setting and poor compliance to medication becomes more of an issue. In fact, he said, a recent study showed that 47% of patients with resistant hypertension were not adherent to their medication regimens.

Also contributing to the smaller reductions in the real-world population is the fact that the average starting blood pressure was lower than in the clinical trials, Mahfoud said, adding that it is known that renal denervation induces greater reductions in blood pressure among those with the highest readings initially.

Mahfoud reported receiving institutional grant/research support from Medtronic, St. Jude, Recor, and serving as a consultant for St. Jude, Medtronic, Boston Scientific, and Cordis. Medtronic makes the Symplicity renal denervation device.

 Primary source: European Association of Percutaneous Cardiovascular Interventions

SOURCE REFERENCE:

Mahfoud F, et al “Early results following renal denervation for treatment of hypertension in a real-world population: the Global SYMPLICITY registry” EuroPCR 2013.

Adverse Events:
Of the first 617 patients included in the registry, only two had vascular complications related to access during the procedure, and none had serious events stemming from delivery of the radiofrequency energy to the renal artery; the rate of vasospasm was 9%, according to Felix Mahfoud, MD, of Saarland University Medical Center in Homburg/Saar, Germany.Through 6 months of follow-up, there were two hospitalizations for hypertensive crisis, two myocardial infarctions, one new case of end-stage renal disease from nephrotoxic overdose, and one death that was not considered to be related to the procedure, he reported at the EuroPCR meeting here.The procedure was not only safe, but also effective at lowering blood pressure, with reductions in office-based readings ranging from 13/6 mm Hg among patients with a baseline systolic blood pressure of 140 mm Hg or higher to 28/18 mm Hg among those with a baseline systolic pressure of 180 mm Hg or higher at 3 months. The findings were similar at 6 months.

“The take-home message will be hopefully … that renal denervation is a safe procedure providing blood pressure lowering in patients with high blood pressure at baseline and that that procedure might have an impact on clinical outcomes,” Mahfoud said in an interview.

Positive Effects of Renal Denervation Ablation for Hypertension in Controlled Randomized SYMPLICITY HTN-2 Trial

Renal Nerve Ablation Effects on BP Lasting

Download Complimentary Source PDF 

By Chris Kaiser, Cardiology Editor, MedPage Today

Published: January 08, 2013
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Late-term results from a study of the safety and effectiveness of renal denervation to reduce hypertension mirrored positive results seen earlier in the randomized SYMPLICITY HTN-2 trial, researchers found.

The mean reduction in systolic blood pressure at 1 year post procedure was a significant 28.1 mmHg (P<0.001), similar to the mean 31.7 mmHg drop at 6 months (P=0.16 for the comparison), according to Murray Esler, MD, of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia, and colleagues.

Those in the control group who crossed over to the intervention at 6 months also had a significant fall in systolic blood pressure from a mean 190 to 166 mmHg (P<0.001), researchers reported in the January issue of Circulation: Journal of the American Heart Association.

The increasing prevalence of hypertension is a worldwide phenomenon, with an estimated 1.56 billion predicted to be affected in 2025, the authors noted. Yet, many of these patients cannot control their blood pressure (with control being defined as a pressure <140/90 mmHg) even when taking three or more antihypertensive medications.

Esler and colleagues cited a 2005 study that found a range of 47% to 87% of people in North America and Europe whose blood pressure is not under control (Lancet 2005; 365: 217-223).

Renal denervation has shown promise in these patients who are refractory to medication. The percutaneous procedure uses energy such as radiofrequency waves to scar the renal artery in an attempt to disrupt the sympathetic nerves, thereby affecting blood pressure.

Three-year data from the nonrandomized SYMPLICITY HTN-1 study were in line with 2- and 1-year results, showing a mean drop of 33/19 mmHg associated with the intervention.

In the current study, researchers from the multi-center randomized controlled SYMPLICITY HTN-2 trial enrolled 106 patients with essential hypertension (systolic blood pressure ≥160 mmHg, or ≥150 mmHg for diabetics). Patients were taking at least three antihypertensive medications.

The initial 1-year data from the SYMPLICITY HTN-2 trial were reported at the 2012 American College of Cardiology meeting. The primary endpoint was a change in systolic blood pressure at 6 months. Also at the 6-month mark, patients in the control group were allowed to cross over and receive the treatment; they were then followed for 6 more months.

The 6-month data were based on 101 patients (49 in the treatment group versus 51 controls). The 1-year data were based on 47 patients in the primary treatment group and 35 per-protocol controls who crossed over. The crossover patients also had to have a systolic blood pressure of ≥160 mmHg.

The significant decrease of 28.1 mmHg in systolic blood pressure in the treatment arm at 1 year was matched by significant drops in diastolic blood pressure at 6 and 12 months, as well as in the crossover group at 6 months (P<0.001 for all).

The authors reported that 84% of initial denervation patients had a decrease of at least 10 mmHg at 6 months; at 1 year, the number was 79%. In the crossover group, that rate was 63% at 6 months.

Interestingly, there was no significant difference in the changes in medication — reduced dosage or fewer drugs — between the treatment arm and controls, despite the reduction in blood pressure for the treatment arm.

“These data further substantiate the safety of renal sympathetic denervation via delivery of controlled radiofrequency energy bursts,” Esler and colleagues concluded.

They also noted that renal function remained unchanged at both 6 and 12 months. A pilot study by the Melbourne group looking specifically at patients with chronic kidney disease found renal denervation to be safe in this population.

The limitations to the current study include the lack of 24-hour blood pressure monitoring and the lack of blinding among the staff measuring blood pressure. The investigators noted that the ongoing SYMPLICITY HTN-3 trial addresses these limitations.

This study was funded by Medtronic Ardian.

Esler and three co-authors reported receiving research support from Medtronic Ardian. During the conduct of the trial, senior author Sobotka was chief medical officer of Ardian, and was a medical adviser to Medtronic.

From the American Heart Association:

 SOURCE:

Other articles on this topic on this Open Access Online Scientific Journal:

Lev-Ari, A. (2012aa). Renal Sympathetic Denervation: Updates on the State of Medicine

https://pharmaceuticalintelligence.com/2012/12/31/renal-sympathetic-denervation-updates-on-the-state-of-medicine/

 

Lev-Ari, A. (2012U). Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

https://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

Lev-Ari, A. (2012C). Treatment of Refractory Hypertension via Percutaneous Renal Denervation

https://pharmaceuticalintelligence.com/2012/06/13/treatment-of-refractory-hypertension-via-percutaneous-renal-denervation/

Read Full Post »


Reported by: Dr. Venkat S. Karra, Ph.D.

Recent study by Margareta Ring, et.al., indicates that Arterial Structure and Function in Mild Primary Hyperparathyroidism Is Not Directly Related to Parathyroid Hormone, Calcium, or Vitamin D.

They found normal arterial function, despite high PTH and Ca as well as low vitamin D levels, in patients with mild PHPT without cardiovascular risk factors.

English: Main complications of persistent high...

The cardiovascular risk associated with low vitamin D and/or high PTH and Ca levels may be explained by their coupling to blood pressure and other risk factors rather than direct effects on the arterial structure, author said. Research findings support the importance of adequate blood pressure control in PHPT if PTX is not performed, but do not indicate vascular abnormalities motivating extended follow-up after PTX.

 

 

Source

Read Full Post »


Treatment of Refractory Hypertension via Percutaneous Renal Denervation 

Curator: Aviva Lev-Ari, PhD, RN

UPDATED  8/5/2013

VIEW VIDEO – Editorial the Heart.org

Renal denervation: Clinical lessons from around the world

Renal Denervation treatment represents a medical subfield, it has its roots in surgical sympathectomy techniques dating back to the 1930s. This radical approach to blood pressure control, which did not specifically target renal nerves, was ultimately abandoned due to associated perioperative complications. However, experience in renal transplantation, a procedure in which the renal nerves are selectively severed, suggests that the denervated kidney can maintain volume and electrolyte homeostasis.

http://ajpregu.physiology.org/content/298/2/R245.full

http://www.ncbi.nlm.nih.gov/pubmed/3326559?dopt=Abstract

Potential effects of renal denervation are on improved glucose control, sleep apnea, and treatment of heart failure syndromes and renal dysfunction – all consequences of sustained hypersympathetic activity.

Based on these observations, the specific targeting of renal nerves as a major operative in the pathophysiology of hypertension and other conditions associated with increased sympathetic activity (renal dysfunction and heart failure) appears to be an attractive therapeutic approach.

http://bmctoday.net/evtoday/2012/02/article.asp?f=renal-artery-denervation-a-brave-new-frontier

A new therapeutic paradigm of percutaneous renal artery denervation using the application of radiofrequency (RF) energy (Symplicity renal denervation system [Ardian, acquired by Medtronic, Inc., Minneapolis, MN]) has recently been demonstrated to be safe, effective, and durable in significantly reducing systolic blood pressure in patients with resistant hypertension.

This new technology represents the first time that physicians have been able to target renal nerves specifically via a catheter-based intervention. This endovascular approach opens the door to better understanding the relationship between sympathetic hyperactivity and hypertension.

Current therapeutic strategies center on lifestyle changes and pharmacologic interventions; however, the rates of blood pressure control and therapeutic efforts to reduce the rate of progression of hypertensive end-organ damage (resulting in myocardial infarction, stroke, and renal dysfunction) remain a neglected priority.

http://rd.springer.com/article/10.1007/s11906-010-0119-1

Renal denervation is used to treat uncontrolled hypertension, or high blood pressure, by the ablation of the nerves that line the renal arteries using a catheter. The Cleveland Clinic called renal denervation the No. 1 healthcare innovation of 2012. More than 12 million patients worldwide whose blood pressure remains uncontrolled despite taking three or more anti-hypertensive medications representing a global market opportunity for renal denervation that could ultimately grow to $30 billion. The Millennium Research Group estimates that the hypertension-treating devices could generate $4.4 billion per year, Bloomberg reported. That number could swell if the FDA indicates the systems for simple hypertension and not just the drug-resistant sort. As Bloomberg notes, a boom in hypertension devices would be a welcome development for the device industry, which has struggled over the past four years with recalls, litigation and regulatory woes, leading to a 7% decline in Standard & Poor’s Healthcare Equipment Index.

“At least 23 companies, mainly smaller, private companies are developing products,” Wang said, based on information she gathered at the American College of Cardiology Conference in Chicago in March.

http://medcitynews.com/2012/04/medtronic-aside-a-whole-host-of-firms-chasing-hypertension-market/

http://www.fiercemedicaldevices.com/story/bloomberg-hypertension-devices-could-pay-big-us/2012-05-25?utm_medium=nl&utm_source=internal

According to the American Heart Association, a 5 mm Hg (millimeters of mercury) reduction in systolic blood pressure results in a 14 percent decrease in stroke, a 9 percent decrease in heart disease, and a 7 percent decrease in overall mortality. Renal denervation has shown in clinical studies to be safe, durable and effective in reducing systolic blood pressure by as much as 20 percent.

Numerous analysts suggest that there are more than 12 million patients worldwide whose blood pressure remains uncontrolled, despite taking three or more anti-hypertensive medications. This represents a global market opportunity for renal denervation approaching $30 billion.

Procedure Benefits

Hypertension, though often asymptomatic, is the number one risk factor for premature death worldwide.1 Renal Denervation (RDN) treatment aims to address this condition at its source to provide a substantial and durable reduction in blood pressure. After the procedure, people can often return to their normal activities quickly. The benefit is often achieved after several weeks to months.

Benefits and New Indications for Usage of Intravascular Stimulation/Ablation of Autonomics

1. Reduction in Heart Rate and Heart Rate Variability

Dr. Scherlag experiments noted changes in heart rate which have also been reported in SYMPLICITY HTN-1 and SYMPLICITY HTN-2 (8-9).  The SYMPLICITY HTN-2 study demonstrated profound bradycardia in 13% of patients that was treated with atropine.

The intra-procedure effect on heart rate during renal artery denervation documented in the  SYMPLICITY trials is also manifest long term by measuring heart rate variability (10). Indeed, cardiac effects would be expected with autonomic modulation.  Besides the two example above showing that cardiac sympathetic denervation effects heart rate, there are many more that are just beginning to be reported in the literature.

These articles shows the effects of renal denervation on heart rate.

http://www.ncbi.nlm.nih.gov/pubmed/1735574
http://www.ncbi.nlm.nih.gov/pubmed/8777835

A Cleveland Clinic review article states: “Additionally, the resting heart rate was lower and heart rate recovery after exercise improved after the procedure, particularly in patients without diabetes.”
http://www.ccjm.org/content/79/7/501.full

2. Renal Sympathetic Denervation lowers Atrial Fibrillation

This article discusses the effect of renal sympathetic denervation on atrial fibrillation.

http://www.ncbi.nlm.nih.gov/pubmed/22585944

3. Regression of Left Ventricular Hypertrophy, Increase in Ejection Fraction (EF) and improved Diastolic Dysfunction

“Brandt reported regression of left ventricular hypertrophy and significantly improved cardiac functional parameters, including increase in ejection fraction and improved diastolic dysfunction, in a study of 46 patients who underwent renal denervation. This findings suggests a potential beneficial effect on cardiac remodeling.” (Brandt MC, Mahfoud F, Reda S, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol 2012; 59:901–909)

4. Reduction in Ventricular Tachyarrhythmias (VT)

“Ukena reported reduction in ventricular tachyarrhythmias in two patients with congestive heart failure who had therapy-resistant electrical storm.” (Ukena C, Bauer A, Mahfoud F, et al. Renal sympathetic denervation for treatment of electrical storm: first-inman experience. Clin Res Cardiol 2012; 101:63–67)

5. Intravascular Stimulation of Autonomics Effects on Heart Failure

The most recent data from Europe shows the following effects on heart failure:

http://www.eurekalert.org/pub_releases/2012-08/esoc-rdg082712.php
http://www.theheart.org/article/1364267.do

Dr. Scherlag, writes, [N]early ten examples of the effects of “CARDIAC SYMPATHETIC DENERVATION” and what are the effects on the kidney?

No change in GFR.  No change in creatinine.

https://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

Procedure Risks

Although major complications are uncommon, RDN treatment carries many of the same risks as an angioplasty procedure for the treatment of artery disease. The catheter insertion site could become infected, become bruised or bleed heavily. Other possible complications include heart attack, stroke, kidney damage or malfunction, heart rhythm disturbances, arterial damage, hypotension, sudden cardiac death, burns and pain. Imaging agents, pain medications and anti-spasm agents are commonly used during the procedure and carry known risks.

1. Mathers, C., et al. World Health Organization; 2009

http://www.ardian.com/ous/patients/benefits-risks.shtml

Medical Debate on the Procedure – The candidates are hypertensive patients receiving blood-pressure-lowering medication that are truly “resistant.”

The Symplicity system (Medtronic) is the far-and-away front runner, having demonstrated average office-based BP drops of 32/12 mm Hg at six months in the SYMPLICITY HTN 2 trial, as reported by heartwire, with 84% of patients having had a >10-mm-Hg drop in systolic blood pressure from baseline.

Upwards of 20 other companies, according to Dr Ron Waksman (Washington Hospital, DC), are busy developing competing systems, some of which were featured in a EuroPCR session devoted to emerging technologies in May 2012 in Paris.

Leading this pack is St Jude’s EnligHTN system, which received CE Mark on the opening day of the meeting. Dr Stephen Worthley (Royal Adelaide Hospital, Australia) presented 30-day results in 47 resistant-hypertension patients treated with the multielectrode, RF-ablation-based system. Mean office BP changes at one month in EnligHTN 1 were -28 systolic and -10 diastolic (p<0.0001 from baseline), with 78% of patients having systolic BP drops of >10 mm Hg.

https://www.massdevice.com/news/europcr-st-judes-enlightn-lowers-blood-pressure-faster-rival-systems

In terms of safety, no serious complications were seen in the renal artery or at the access site in the EnligHTN study; minor procedure-related events included four hematomas, three vasovagal responses to sheath removal, and two postprocedure transient bradycardias.

Other devices featured in the session included a second RF-energy system and two ultrasound systems, see below technology description by supplier.

The risk of cardiovascular death doubles with every 20 point increase in systolic blood pressure, so an average blood pressure reduction of 28 points is quite significant and demonstrates just how effective the technology is. Principal investigator Prof. Stephen Worthley said in prepared remarks. “From other clinical trials studying the impact of renal denervation we have learned that blood pressure continues to be reduced over time, so I would not be surprised to see this trend continue and see an even greater benefit for patients.” St. Jude’s study included 47 patients with high blood pressure that wasn’t managed with drug therapy. Participants had an average of 176/96 mmHg baseline blood pressure, despite taking multiple medications, before the denervation procedure and an average of 148/87 mmHg after. More than 40% had systolic rates below 140 mmHg.

http://investors.sjm.com/phoenix.zhtml?c=73836&p=irol-newsArticle&ID=1695802

Interventionalists who spoke with heartwire were unvaryingly excited about the potential of renal denervation, with some caveats.

“You need enthusiasm to develop new things, and in hypertension we haven’t seen an innovation in decades,” Dr Thomas Lüscher (University Hospital Zürich, Switzerland) told heartwire. “So just the possibility that you would be able to have a persistent treatment effect by a procedure that helps severe hypertension patients and maybe in the future even the option to cure hypertension is very exciting indeed. But I agree it’s a dream at this point. I think we need the SYMPLICITY HTN 3 trial, which hopefully will confirm what the other studies have shown.”

Now enrolling at as many as 90 US centers, SYMPLICITY HTN 3, Lüscher pointed out, has design characteristics addressing two concerns with the earlier trials, namely a sham procedure for the control group and ambulatory blood-pressure monitoring in all patients.

During the same emerging-technologies session, Lüscher explored the albeit-scant data supporting a role for renal denervation in other conditions: everything from metabolic syndrome and obstructive sleep apnea to heart failure, atrial fibrillation, and polycystic-ovary syndrome.

But his counterpoint, Dr Jean Renkin (UCL St Luc University Hospital, Brussels, Belgium), was skeptical, pointing to the myriad unanswered questions with the technology.

“Currently, reasonably solid data are available only for patients with hypertension resistant to pharmacotherapy, which cannot necessarily be extrapolated to other forms of hypertension or conditions referred to [by Dr Lüscher]. However, at this point in time, no clouds have appeared in the sky, so let us dream on.”

Dr Renkin had one staggering number for the audience to consider: of 5000 patients who have undergone renal denervation, only 250 were actually treated as part of clinical studies. While no device has US approval, five denervation systems already hold CE Mark in Europe and are being used with increasing frequency.

Treating the Truly Medication Treatment “Resistant”

For a comprehensive presentation of Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes, refer to

https://pharmaceuticalintelligence.com/2012/05/29/445/

Another talking point is the proportion of patients who are truly “resistant.” The number agreed on by Lüscher, Waksman, and session comoderator Dr Robert Whitbourn (St Vincent’s Hospital, Fitzroy, Australia) was that just 3% of all hypertensive patients receiving blood-pressure-lowering medication are truly “resistant.” Numbers as high as 30% have been suggested in other reports, he noted.

“Interestingly, when we’ve been involved in various trials, every cardiologist says they have hundreds of these patients, but when we actually go to get them, no one actually has any,” Whitbourn quipped. “I think it should be a sobering thought—the numbers are actually quite small.”

Dr William Wijns (Cardiovascular Center Aalst, Belgium), also speaking with heartwire, agreed that the subset was “small” but argued it was “still big numbers, millions of people,” and “a massive unmet need.”

Waksman, insisting he was “excited” by what he called “robust reductions in blood pressure,” nevertheless urged eager interventionalists to work with hypertension experts and resist the urge “to jump on patients before we truly verify that they are resistant to medical treatment.”

In the vast majority of people even for whom renal denervation is appropriate, it “won’t be a cure,” Waksman said. “Most of these patients will have to continue on medical treatment—this is not replacing medical treatment, it is just getting [patients] more in control.”

http://www.theheart.org/article/1402321/print.do

The Global Supplier Ecosystem for Renal Denervation Systems

US Campbell, CA Kona Medical is attempting to address these limitations. The system delivers energy from outside the patient to the renal nerves. Ultimately, the procedure will be a “no puncture,” noninvasive technique, compatible with technologies that will allow for temperature and lesion mapping. A noninvasive procedure will allow titration of the therapy— that is, the application of patient-specific dose fractions while monitoring therapeutic effect in between fractions. The basis of the technology is focused ultrasound, not high intensity (HIFU) as one might see and expect in the treatment of tumors, but low-intensity focused ultrasound (LIFU). The biologic underpinnings of this treatment are described in past literature for treating nerves using ultrasound. Kona noninvasive system. The system is depicted in a custom chair; another version of the system is compatible with a standard fluoroscopy or MRI table. Both ultrasound (through elastography and the evolution of temperature mapping and MRI) allow further imaging and analysis of the treatment area. The dose distribution surrounding the artery is that of an annular ring around the wall of the artery. Kona has shown in animal studies that a heat/vibratory cloud at one plane along the artery is highly effective at long-term inhibition of renal nerves with no visible effect on any portion of the artery at any time point.

US, Ronkonkoma, NY & Germany – Paradise  by ReCor Medical 6-F compatible catheter with a cylindrical transducer that emits ultrasound energy circumferentially, allowing for a more efficient renal denervation procedure First-in-human (15 patients at 3 months) BP drop, mm Hg -32/-16 at 3 mo. The ultrasound transducer lies within a low-pressure balloon that allows for self-centering of the transducer and gentle contact with the artery wall for uniform circumferential denervation. This means that nerves below the surface of the artery wall are damaged in 360° with a single emission. The balloon also enables cooled fluid to circulate during the energy delivery process, thereby cooling the endothelial wall and protecting it from any excessive heating that could be caused by other energy sources or designs. Preliminary F-I-M clinical data for PARADISE were reported previously at the “TRenD 2012” transcatheter renal denervation scientific meeting by cardiologist Thomas A. Mabin, M.D., Vergelegen Medi-Clinic, South Africa. The updated PARADISE data show that systolic blood pressure was reduced by a statistically significant average of 36 mm Hg in 8 patients at 90-days follow-up. The scientific literature demonstrates that only a 5 mm Hg reduction in BP results in a 14% decrease in stroke, a 9% decrease in heart disease, and a 7% decrease in mortality.

US, San Leandro, CA The Mercator Bullfrog by Mercator MedSystems, Inc. is a catheter-guided system designed to inject therapeutic agents directly, nonsystemically, and safely through blood vessel walls into adventitial tissues and has received US Food and Drug Administration 510(k) clearance. The Bullfrog catheter is tipped with a balloon-sheathed microneedle and is guided and inflated in a manner similar to an angioplasty catheter but with far lower expansion pressures (2 atm vs 6–20 atm) in vessels of 3 to 6 mm in diameter. It is compatible with 0.014-inch guidewires and 6-F introducer sheaths. When the desired injection site is reached, the balloon is inflated with saline and radiopaque contrast, securing the system for injection and sliding the microneedle through the vessel wall. Nonclinical studies have shown that the Bullfrog catheter is able to deliver up to 5 mL per injection into the renal artery adventitia with no apparent safety concerns. Guanethidine Ismelin) is delivered to the renal artery adventitia to accomplish sympathetic denervation. Given locally, guanethidine is known to induce an autonomic denervation directly and through an immune-mediated pathway. Mercator’s preclinical experiments have shown that guanethidine, injected at appropriate concentrations into the adventitial space around renal arteries, selectively ablates the nerves in the adventitia around the renal artery after a single, 20-minute procedure

J Neurosci. 1983;3:714-724

US – Laguna Hills, CA – V2 Radiofrequency Baloon by Vessix Vascular, Inc. Bipolar RF balloon catheter REDUCE-HTN pilot (10 patients)

BP drop, mm Hg -30/-11 at 1 mo V 2 catheter, a patented noncompliant balloon catheter with RF electrodes and thermistors mounted on the exterior of the balloon, and the proprietary V 2 bipolar RF generator. Once inserted into the renal artery, a 30-second inflation/treatment per renal artery delivers simultaneous RF therapy with independent temperature control to all electrode pairs. V 2 catheter is available in balloon diameters ranging from 4 to 7 mm, with a balloon length of 25 mm. Larger-diameter balloons have eight electrode pairs, and smaller-diameter balloons have four to six electrode pairs made of solid gold, which are biocompatible and facilitate good electrode contact with the renal arterial wall. In addition, the electrodes are radiopaque, allowing the V 2 catheter to be easily visualized under fluoroscopy. Beginning in the first quarter of 2012, the V 2 renal denervation system will be utilized in the company’s first international, multicenter clinical study: REDUCEHTN.

Israel, Tel Aviv – Tivus by Cardiosonic  A6-F transducer-tipped catheter, ultrasound energy (Animal data only) The solution for renal denervation is a high-intensity, nonfocused ultrasonic (US) catheter system named TIVUS (Therapeutic IntraVascular UltraSound) (Figure 3). By applying ultrasonic energy, the TIVUS technology enables remote, localized, controlled, and repeatable thermal modulation of the renal vessel wall tissue, resulting in safe renal nerve ablation. The remote thermal effect is located in the adventitia and perivascular region, with no thermal damage to the endothelium and media, therefore, preventing the development of vessel injury processes. Swine kidney tissue NE concentrations at 30- and 90-day follow-up have demonstrated successful renal denervation as witnessed by a 50% or more decline in tissue NE. Localized tissue thermal modulation/ablation, without damage to the blood vessel wall.

US, MN – SYMPLICITY HTN 2 by Medtronic   average office-based BP drops of BP drop, mm Hg 32/12 mm Hg at six months in the SYMPLICITY HTN 2 trial, as reported by heartwire, with 84% of patients having had a >10-mm-Hg drop in systolic blood pressure from baseline. 14 points in 30 days and 27 points after 1 year. Available in Europe. Medtronic is the furthest ahead in its development process, predicting it will get Symplicity on the American market by 2015. catheter in the renal artery near each kidney to deliver radiofrequency energy to ablate the nerves. A single electrode in contrast to St. Jude’s mutli-electrode approach, is already on the road to FDA review with clinical trials approved last summer in the U.S. Symplicity system has been safely used in nearly 5,000 patients since commercialization

US, MN – EnligHTN 1 by  St Jude radiofrequency (RF) energy to create lesions (tiny scars) along the renal sympathetic nerves Mean office BP changes at one month in BP drop, mm Hg 28 systolic and -10 diastolic after 1 month (p<0.0001 from baseline), with 78% of patients having systolic BP drops of >10 mm Hg. St. Jude Medical’s (St. Paul, MN) announcement in late 2011 of the first patient to be enrolled in their first-in-man ARSENAL trial 15 at the University of Adelaide

Ireland, Dublin – OneShot™ by Covidien acquisition of Maya Medical, Saratoga, CA New Irrigated RF Balloon Catheter secure first human use for the device in the third quarter of this year, followed by a CE mark for the drug-resistant hypertension treatment in 2013. Presumably, a filing with the FDA would follow that. the OneShot renal denervation system, was born out of the company’s extensive expertise in radiofrequency (RF) ablation and percutaneous coronary interventions (PCI), drawing upon the benefits and best practice standards of each distinct yet complementary clinical discipline. The result is a unique product platform that could further accelerate the paradigm shift in the management of resistant hypertension. consistent with Maya’s balloon-based approach is the ability to deliver predictable apposition of the RF electrode to the vessel wall for more controlled targeted delivery of the RF energy. By offering a more reliable single-treatment approach coupled with enhanced ease of use and reduced procedure times, Maya Medical believes its OneShot renal denervation system has the potential to significantly expand clinical adoption

http://bmctoday.net/evtoday/2012/02/article.asp?f=renal-artery-denervation-a-brave-new-frontier

US, Natick, MA Boston Scientific lags behind in the race to cash in on hypertension-treating devices, incoming CEO Michael Mahoney said at a Monday conference that it has a plan for its RDN renal denervation system. As MassDevice reports, Mahoney said Boston Sci expects to secure first human use for the device in the third quarter of this year, followed by a CE mark for the drug-resistant hypertension treatment in 2013.

St Jude’s EnligHTN system

Said Frank Callaghan, president of the St. Jude Medical Cardiovascular Division “This launch is important because it represents a significant growth opportunity and exemplifies our commitment to advancing the practice of medicine. We’ve applied the decades of insight we’ve gained from developing successful ablation technologies that treat cardiac arrhythmias to establish an innovative solution for hypertension.” With the unique basket design, each placement of the ablation catheter allows a consistent and predictable pattern of four ablations in 90-second intervals. Compared to single electrode ablations, the multi-electrode EnligHTN system has the potential to improve consistency and procedural reliability, save time as well as result in workflow and cost efficiencies. Additionally, the minimal catheter repositioning may result in a reduction of contrast and fluoroscopic (x-ray) exposure. The technology includes a guiding catheter, ablation catheter and ablation generator. The generator uses a proprietary, temperature-controlled algorithm to deliver effective therapy.

http://investors.sjm.com/phoenix.zhtml?c=73836&p=irol-newsArticle&ID=1695802

http://medgadget.com/2012/05/st-jude-medical-launches-enlightn-renal-denervation-system.html

St Jude’s EnligHTN system – view video

http://www.sjmprofessional.com/Products/Intl/Renal-Ablation-Therapy/enlightn-renal-denervation-system.aspx

Covidien

Unveiled a Novel Renal Denervation System OneShot™ at EuroPCR congress in Paris on 5/16/2012. “Live” Cases with New Irrigated RF Balloon Catheter for Treatment of Medication-resistant Hypertension and poor outcomes of pharmacological agents. The OneShot system is an irrigated, radiofrequency (RF) based balloon catheter used to ablate the renal sympathetic nerves located in the outer wall of the renal arteries. The OneShot technology received CE mark clearance in February 2012.

The OneShot system was featured in “live” cases at the Covidien-sponsored “Tools & Techniques (TNT) Interventions” presentation and panel session for hypertension and renal denervation at the EuroPCR congress. Professor Dirk Scheinert performed two cases at Park Hospital in Leipzig, Germany, that were transmitted live at the Palais des Congrès de Paris. In addition, John Ormiston, MD, Medical Director for Mercy Angiography and President of the Asia-Pacific Society of Interventional Cardiology in New Zealand, presented first-in-human results of cases performed with the OneShot system in New Zealand. The OneShot system and Covidien’s other endovascular solutions was on display at the EuroPCR meeting.

Additional faculty in the TNT session is a distinguished group of speakers including:

Professor Karl-Heinz Kuck, MD, F.A.C.C. – Director, Cardiology Department
Allgemeines Krankenhaus St. Georg – Hamburg, Germany

Dr. Stephen R. Ramee, FACC, FSCAI
Ochsner Medical Center – New Orleans, Louisiana

Dr. John Ormiston, MBChB, FRACP – Medical Director
Mercy Hospital Angiography Unit – Auckland, New Zealand

Professor Marc Sapoval, MD, PhD – Department Head
Cardiovascular/Interventional Radiology – Hospital Pompidou University – Paris, France

Dr. Renu Virmani – Medical Director
CVPath Institute – Gaithersburg, Maryland

Covidien discloses that it purchased Maya Medical for $60 million in cash on April 20. If Maya Medical meets certain regulatory and sales milestones, it will receive up to an additional $170 million. Covidien notes that Maya Medical’s OneShot system received the CE Mark in February.

MedCity News was the first to report Covidien’s interest in Maya Medical on 5/8/2012.

In a note to investors Monday, analyst Bob Hopkins of Bank of America said that renal denervation “has the potential to be one of the largest new markets in medtech over the next 2-4 years and for [Covidien] this looks like another small deal with big potential.”

http://medcitynews.com/2012/05/covidien-discloses-60m-purchase-of-hypertension-treatment-firm/?edition=medical-devices

Clinical Trial for RAPID is ongoing

 Rapid Renal Sympathetic Denervation for Resistant Hypertension (RAPID)

This study is currently recruiting participants.

Verified June 2012 by Maya Medical

First Received on January 25, 2012.   Last Updated on June 4, 2012   History of Changes

Sponsor: Covidien (Maya Medical)
Collaborator: Meditrial Europe LTD
Information provided by (Responsible Party): Maya Medical
ClinicalTrials.gov Identifier: NCT01520506

  Purpose

Maya Medical OneShot™ Ablation System use is to deliver low-level radio frequency (RF) energy through the wall of the renal artery to denervate the human kidney.

Condition Intervention Phase
Hypertension, Resistant to Conventional Therapy Device: Maya Medical OneShot Phase 2
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy StudyIntervention Model: Single Group AssignmentMasking: Open LabelPrimary Purpose: Treatment
Official Title: Rapid Renal Sympathetic Denervation for Resistant Hypertension Using the Maya Medical OneShot™ Ablation System

http://www.clinicaltrials.gov/ct2/results?term=Renal+Denervation&pg=2&show_flds=Y

Covidien into direct competition with Medtronic, whose Symplicity renal denervation system is approved in Europe. Currently, the system is being tested in the U.S. St. Jude Medical, Medtronic’s in-state rival, is also developing a therapy and that is expected to have a limited European market launch before the end of the year. But it is not only the larger players that Covidien will have to play against in Europe. A whole host of companies is developing products there, including ReCor Medical.

http://www.canada.com/entertainment/ReCor+Medical+discloses+data+from+clinical+study+PARADISE+ultrasound/6430884/story.html

Medtronic

Medical device giant Medtronic (NYSE: MDT), November 23, 2010 said it has agreed to pay $800 million upfront, plus commercial milestone payments through 2015, to acquire Mountain View, CA-based Ardian. Medtronic had previously built up an 11 percent ownership stake in Ardian, when it invested with its venture backers, which include Morgenthaler Ventures, Advanced Technology Ventures, Split Rock Partners, and Emergent Medical Partners. Ardian’s windfall comes about one week after it presented some eye-opening clinical trial results in The Lancet, and at the American Heart Association’s scientific meeting.

http://www.xconomy.com/san-francisco/2010/11/23/medtronic-buys-ardian-for-800m-upfront-grabs-novel-treatment-for-high-blood-pressure/

Clinical Trial for SYMPLICITY is ongoing.

Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN-3)

This study is currently recruiting participants.

Verified June 2012 by Medtronic Vascular

First Received on August 15, 2011.   Last Updated on June 11, 2012   History of Changes

Sponsor: Medtronic Vascular
Information provided by (Responsible Party): Medtronic Vascular
ClinicalTrials.gov Identifier: NCT01418261

  Purpose

The Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study of the safety and effectiveness of renal denervation in subjects with uncontrolled hypertension. Bilateral renal denervation will be performed using the Symplicity Catheter – a percutaneous system that delivers radiofrequency (RF)energy through the luminal surface of the renal artery.

Condition Intervention Phase
Uncontrolled Hypertension Device: Renal denervation (Symplicity Catheter System) Phase 3
Study Type: Interventional
Study Design: Allocation: RandomizedEndpoint Classification: Safety/Efficacy StudyIntervention Model: Parallel AssignmentMasking: Single Blind (Subject)Primary Purpose: Treatment

http://clinicaltrials.gov/ct2/show/NCT01418261

 The Symplicity™ Renal Denervation System has two main components:

The elements are designed to work together as an integrated system to ensure consistent performance:

Symplicity™ Catheter – Low profile, endovascular energy delivery catheter

Symplicity™ Generator – Automated, portable RF generator

The Symplicity Renal Denervation System uses controlled, low-power radiofrequency (RF) energy to deactivate the renal nerves, thereby selectively reducing both the pathologic central sympathetic drive to the kidney and the renal contribution to central sympathetic hyperactivity. The outcome, we hope, will be a significant and sustained reduction in both blood pressure and the level of systemically damaging neurohormones. Since the endovascular procedure does not involve an implant, patients recover quickly and can soon return to their daily living. The device may usher in a new era in the treatment of hypertension, hopefully allowing a one-time procedure to offer patients a long-lasting benefit.

Medtronic Procedure – view video

http://www.ardian.com/ous/medical-professionals/procedure.shtml

Conclusions

The entire industry subsegment is awaiting the results of SYMPLICITY HTN-3. Forecasts of market share by supplier will be predicated on this Clinical Trial completion.

Shutting down overactive nerves around the kidneys as a strategy for fighting resistant hypertension is “one of the most exciting growth markets in medical devices,” Sean Salmon, vice president and general manager of Medtronic’s coronary and peripheral business, said in a statement.

I had a piece in these pages last week about what kind of difference the Ardian treatment was making. The most recent Ardian study showed the new treatment, in combination with standard drugs, was able to bring average blood pressure scores down from 178 over 97 to 146 over 85 after six months of follow-up, while those who just got standard treatments were essentially unchanged. The results were “a big achievement,” according to Murray Esler, the study’s principal investigator.

http://www.xconomy.com/san-francisco/2010/11/23/medtronic-buys-ardian-for-800m-upfront-grabs-novel-treatment-for-high-blood-pressure/

Resources

REFERENCES for Dr. Scherlag’s 1999 Patent and pioneering work on Intravascular Stimulation/Ablation of Autonomics

1. Schauerte P, Scherlag BJ, Scherlag MA, Goli S, Jackman WM, Lazzara R. Transvenous parasympathetic cardiac nerve stimulation: an approach for stable sinus rate control. J Electrophysiol. 1999 Nov;10(11):1517-24.

2. Schauerte P, Scherlag BJ, Scherlag MA, Goli S, Jackman WM, Lazzara R. Ventricular rate control during atrial fibrillation by cardiac parasympathetic nerve stimulation: a transvenous approach. J Am Coll Cardiol. 1999 Dec;34(7):2043-50.

3. Schauerte P, Scherlag BJ, Pitha J, Scherlag MA, Reynolds D, Lazzara R, Jackman WM. Catheter ablation of cardiac autonomic nerves for prevention of vagal atrial fibrillation. Circulation. 2000 Nov 28;102(22):2774-80.

4. Scherlag MA, Scherlag BJ, Yamanashi W, Schauerte P, Goli S, Jackman WM, Reynolds D, Lazzara R. Endovascular neural stimulation via a novel basket electrode catheter: comparison of electrode configurations. J Interv Card Electrophysiol. 2000 Apr;4(1):219-24.

5. Scherlag BJ, Yamanashi WS, Schauerte P, Scherlag M, Sun YX, Hou Y, Jackman WM, Lazzara R. Endovascular stimulation within the left pulmonary artery to induce slowing of heart rate and paroxysmal atrial fibrillation. Cardiovasc Res. 2002 May; 54(2):470-5.

6. Hasdemir C, Scherlag BJ, Yamanashi WS, Lazzara R, Jackman WM. Endovascular stimulation of autonomic neural elements in the superior vena cava using a flexible loop catheter. Jpn Heart J. 2003 May;44(3):417-27.

7. Webster W Jr, Scherlag BJ, Scherlag MA, Schauerte P. Method and apparatus for   transvascular treatment of tachycardia and fibrillation. US Patent 6,292,695. Filed June 17, 1999.

8. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275-1281.

9. Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903-1909.

10. Frank Himmel MD, Joachim Weil MD, Michael Reppel MD, Kai Mortensen MD, Klaas Franzen, Leidinger Ansgar MD, Heribert Schunkert MD, Frank Bode MD.  Improved Heart Rate Dynamics in Patients Undergoing Percutaneous Renal Denervation. Letter to the Editor. JCH. 31 MAY 2012.1751-7176.

Sympathetic Hyperactivity & Hypertension

For more information on hypertension, please visit the medical professional hypertension portal at TheHeart.org .

Siddiqi L, Joles JA, Grassi G, Blankestijn PJ. Is kidney ischemia the central mechanism in parallel activation of the renin and sympathetic system? J Hypertens. 2009 Jul;27(7):1341-9.

Augustyniak RA, Tuncel M, Zhang W, Toto RD, Victor RG. Sympathetic overactivity as a cause of hypertension in chronic renal failure. J Hypertens. 2002;20(1):3-9.

DiBona GF. Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens. 2002;11(2):197-200.

Mancia G, Grassi G, Giannattasio C, Seravalle G. Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension. 1999;34(4 Pt 2):724-728.

References in Scientific Journals about Renal Denervation Treatment

Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903-1909.

Symplicity HTN-1 Investigators. Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension – Durability of Blood Pressure Reduction Out to 24 Months. Hypertension. Volume 57, Number 5, May 2011.

Rippy, M. et al. Catheter-Based Renal Sympathetic Denervation: Chronic Preclinical Evidence for Renal Artery Safety. Clin Res Cardiol. 2011 Dec; 100(12): Pages 1095-1101.

Mahfoud, F. et al. Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension. Circulation. Volume 123, No. 18, May 10, 2011. Pages 1940-1946.

Witkowski A., et al. Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients with Resistant Hypertension and Sleep Apnea. Hypertension. Volume 58, Number 4, October 2011. Pages 559-565.

Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275-1281.

Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal Sympathetic-Nerve Ablation for Uncontrolled Hypertension. N Engl J Med. 2009;361(9):932-934.

Schlaich MP, Sobotka PA, Krum H, Whitbourn R, Walton A, Esler MD. Renal Denervation as a Therapeutic Approach for Hypertension. Novel Implications for an Old Concept. Hypertension. 2009;54(6):1195-1201.

Esler M. The 2009 Carl Ludwig Lecture: pathophysiology of the human sympathetic nervous system in cardiovascular diseases: the transition from mechanisms to medical management. J Appl Physiol. 2010;108(2):227-237.

Dibona GF, Esler MD. Translational Medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298(2):R245-253.

Katholi RE, Rocha-Singh KJ. The role of renal sympathetic nerves in hypertension: has percutaneous renal denervation refocused attention on their clinical significance? Prog Cardiovasc Dis. 2009;52(3):243-248.

Doumas M, Faselis C, Papademetriou V. Renal Sympathetic Denervation and Systemic Hypertension. Am J Cardiol. 2010;105(4):570-576.

Schlaich MP, Krum H, Sobotka PA. Renal sympathetic nerve ablation: the new frontier in the treatment of hypertension. Curr Hypertens Rep. 2010;12(1):39-46.

Katholi RE, Rocha-Singh KJ, Goswami NJ, Sobotka PA. Renal nerves in the maintenance of hypertension: A potential therapeutic target. Curr Hypertens Rep. 2010;12:196-204.

Esler MD, Lambert EA, Schlaich M, Navar LG. The Dominant Contributor to Systemic Hypertension: Chronic Activation of the Sympathetic Nervous System vs Activation of the Intrarenal Renin-Angiotensin System. J Appl Physiol. 2010.

Fisher JP, Fadel PJ. Therapeutic strategies for targeting excessive central sympathetic activation in human hypertension. Exp Physiol. 2010;95(5):572-580.

Malpas SC. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev. 2010;90:513-557.

Lambert GW, Straznicky NE, Lambert EA, Dixon JB, Schlaich MP. Sympathetic nervous activation in obesity and the metabolic syndrome–causes, consequences and therapeutic implications. Pharmacol Ther. 2010;126:159-172.

Masuo K, Lambert GW, Esler MD, Rakugi H, Ogihara T, Schlaich MP. The role of sympathetic nervous activity in renal injury and end-stage renal disease. Hypertens Res. 2010;33:521-528.

Schlaich MP, Socratous F, Hennebry S, Eikelis N, Lambert EA, Straznicky N, Esler MD, Lambert GW. Sympathetic activation in chronic renal failure. J Am Soc Nephrol. 2009;20(5):933-939.

Bock JS, Gottlieb SS. Cardiorenal syndrome: New perspectives. Circulation. 2010;121:2592-2600.

Goldsmith SR, Sobotka PA, Bart BA. The sympathorenal axis in hypertension and heart failure. Journal of Cardiac Failure. 2010;16(5):369-373.

Grassi G. Assessment of sympathetic cardiovascular drive in human hypertension: achievements and perspectives. Hypertension. 2009;54(4):690-697.

Ritz E. New approaches to pathogenesis and management of hypertension. Clin J Am Soc Nephrol. 2009;4(12):1886-1891.

Ritz E, Rump LC. Control of sympathetic activity–new insights; new therapeutic targets? Nephrol Dial Transplant. 2010;25(4):1048-1050.

Joyner MJ, Charkoudian N, Wallin BG. Sympathetic nervous system and blood pressure in humans: Individualized patterns of regulation and their implications. Hypertension. 2010;56:10-16.

Mann JF. Whats new in hypertension 2009? Nephrol Dial Transplant. 2010;25(1):37-41.

Bravo EL, Rafey MA, Nally JV, Jr. Renal denervation for resistant hypertension. Am J Kidney Dis. 2009;54(5):795-797.

King A. Hypertension: RF ablation of renal nerves. Nature Reviews Nephrology. 2009;5:364.

Doumas M, Douma S. Interventional management of resistant hypertension. Lancet. 2009;373(9671):1228-1230.

Paulis L. Novel therapeutic targets for hypertension. Nat Rev Cardiol. 2010.

OBrien E. Renal sympathetic denervation for resistant hypertension. Lancet. 2009;373(9681):2109; author reply 2109-2110.

Titze S, Uder M, Schmieder R. Renal nerve ablation: innovative therapy for treatment of resistant hypertension. MMW Fortschr Med. 2009;151(42):52-53.

Katona PG. Biomedical engineering in heart-brain medicine: A review. Cleve Clin J Med. 2010;77 Suppl 3:S46-50.

Abstracts about Renal Denervation Treatment

Schlaich M, Krum H, Walton T, Whitbourn R, Sobotka P, Esler M. Two-year durability of blood pressure reduction with catheter-based renal sympathetic denervation. Journal of Hypertension. 2010;28:e446.

Esler M, Schlaich M, Sobotka P, Whitbourn R, Sadowski J, Bartus K, et al. Catheter-Based Renal Denervation Reduces Total Body and Renal Noradrenaline Spillover and Blood Pressure in Resistant Hypertension. Journal of Hypertension. 2009;27(suppl 4):s167.

Schlaich MP, Krum H, Whitbourn R, Walton T, Lambert GW, Sobotka PA, et al. Effects of Renal Sympathetic Denervation on Noradrenaline Spillover and Systemic Blood Pressure in Patients with Resistant Hypertension. Journal of Hypertension. 2009;27(suppl 4):s154.

Schlaich M, Krum H, Walton T, Lambert E, Lambert G, Sobotka P, et al. A Novel Catheter Based Approach to Denervate the Human Kidney Reduces Blood Pressure and Muscle Sympathetic Nerve Activity in a Patient with End Stage Renal Disease and Hypertension. Journal of Hypertension. 2009;27(suppl 4):s437.

 

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Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

Curator: Aviva Lev-Ari, PhD, RN

 

Excellent review of Hypertension Medications is provided in the following two short videos:

VIEW VIDEOS

Hypertension Explained Clearly! 1 of 2

Hypertension Explained Clearly! 2 of 2

 

http://www.drugs.com/clinical_trials/new-data-shows-investigational-triple-antihypertensive-combination-therapy-significantly-lowers-9712.html

Hypertension Treatment in the Last Decade

 The need for combination drug therapy was recognized in 2000, In Combination Antihypertensive Drugs: Recommendations for Use

NEIL S. SKOLNIK, M.D., JONATHAN D. BECK, M.D., MATHEW CLARK, M.D., Abington Memorial Hospital, Jenkintown, Pennsylvania

Am Fam Physician. 2000 May 15;61(10):3049-3056

Combination Medication: Impact on Compliance

Increased Compliance with fewer pills a favorable outcome of combination medication for Hypertension.

More medications, fewer pills: Combination medications for the treatment of hypertension Richard Lewanczuk, MD PhD1 and Sheldon W Tobe, MD2

Can J Cardiol. 2007 May 15; 23(7): 573–576.

Classification of Blood Pressure

Category SBP mmHg DBP mmHg

Normal <120 and <80

Prehypertension 120–139 or 80–89

Hypertension, Stage 1 140–159 or 90–99

Hypertension, Stage 2 ≥160 or ≥100

Principles of Hypertension Treatment

• Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients

with diabetes or chronic kidney disease.

• Majority of patients will require two medications to reach goal.

Without Compelling Indications

Stage 1

Hypertension

(SBP 140–159 or DBP

90–99 mmHg)

Thiazide-type diuretics

for most. May consider

ACEI, ARB, BB, CCB,

or combination.

 Stage 2

Hypertension

(SBP ≥160 or DBP

≥100 mmHg)

2-drug combination for

most (usually thiazidetype

diuretic and ACEI,

or ARB, or BB, or CCB).

Causes of Resistant Hypertension

• Improper BP measurement

• Excess sodium intake

• Inadequate diuretic therapy

• Medication

– Inadequate doses

– Drug actions and interactions (e.g., nonsteroidal anti-inflammatory drugs

(NSAIDs), illicit drugs, sympathomimetics, oral contraceptives)

– Over-the-counter (OTC) drugs and herbal supplements

• Excess alcohol intake

• Identifiable causes of hypertension (see reverse side)

Compelling Indications for Individual Drug Classes

 Compelling Indication  and Initial Therapy Options

• Heart failure THIAZ, BB, ACEI, ARB, ALDO ANT

• Post myocardial infarction BB, ACEI, ALDO ANT

• High CVD risk THIAZ, BB, ACEI, CCB

• Diabetes THIAZ, BB, ACEI, ARB, CCB

• Chronic kidney disease ACEI, ARB

• Recurrent stroke prevention THIAZ, ACEI

Key: THIAZ = thiazide diuretic, ACEI= angiotensin converting enzyme inhibitor, ARB = angiotensin receptor

blocker, BB = beta blocker, CCB = calcium channel blocker, ALDO ANT = aldosterone antagonist

http://www.nhlbi.nih.gov/guidelines/hypertension/phycard.pdf

JNC-7 on Treatment for Hypertension

According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, or JNC-7, most people require more than one medication to achieve treatment goals. Some medications are being manufactured in combinations, which reduces the number of pills a patient must take and may reduce costs.

http://www.livestrong.com/article/217562-combination-drugs-for-hypertension/#ixzz1wD1wneZg

All combination drugs for Hypertension are presented in

http://www.livestrong.com/article/217562-combination-drugs-for-hypertension/#ixzz1wD3dqnrl

JNC-7 lists the following Combinations of Drugs for Hypertension:

ACE Inhibitors and Calcium Channel Blockers

The angiotensin converting enzyme inhibitors, or ACEIs, are a group of drugs that work in the kidneys to block a reaction that leads to tightening of the blood vessels and retention of sodium and water. They lower blood pressure by counteracting these effects.

Calcium channel blockers, or CCBs, work by relaxing smooth muscle in the heart and blood vessels. One common side effect of this group of drugs is leg swelling. This can be lessened when they are used in combination with the ACEIs.
Amlodipine-benazepril, enalapril-felodipine and trandolapril-verapamil are examples of these medicines that have been combined into a single pill. Multiple dosing variations are available.

ACE Inhibitors and Diuretics

Diuretics are commonly known as “water pills” because they work by increasing urine output and lowering blood volume, and therefore blood pressure. Diuretics are generally inexpensive, work well to enhance the effects of other medicines and have a proven track record in preventing cardiovascular complications of hypertension, as discussed in JNC-7.

Many ACE inhibitors are available packaged with hydrochlorothiazide, or HCTZ. Benazepril, enalapril, lisinopril and others are commonly seen in this combination.

ARBs and Diuretics

The angiotensin receptor blockers, or ARBs, are related to the ACEIs, in that they work on the same renal pathway. However, the ARBs work farther down the process and often have fewer side effects. The beneficial effects on blood pressure are similar between the two groups.

Candesartan, losartan, telmesartan, valsartan and others are available as combination drugs with HCTZ.

Beta-blockers and Diuretics

Beta-blocking medications work in the peripheral nervous system to slow the heart rate and decrease adrenalin-type effects on the blood vessels. JNC-7 notes that the beta-blockers are especially useful in those with hypertension and heart disease or angina.

Atenolol is available with the diuretic chlorthalidone, which is similar to HCTZ. Bisoprolol, metroprolol, propranolol LA and timolol come in combination with HCTZ.

Centrally Acting Drugs and Diuretics

Methyldopa and reserpine affect the central nervous system to produce a lowering of blood pressure. They are not used often, but can be effective in the appropriate situation. Each come in a combination drug with HCTZ, while reserpine is also produced with chlorthalidone and chlorothiazide.

Diuretic Combinations

Various diuretics work in different locations of the kidneys to affect their anti-hypertensive properties. HCTZ tends to lower blood potassium, so is available in combination with spironolactone or triamterene, which are known to elevate potassium. The combination tends to be potassium neutral.

ARB and Calcium Channel Blocker and Diuretic

In July 2010, a triple combination drug for hypertension was approved by the US Food and Drug Administration. Tribenzor contains olmesartan medoxomil, amlodipine and hydrochlorothiazide, according to Monthly Prescribing Reference.

Three Combination Drug Therapy for Antihypertension from Daiichi Sankyo’s Portfolio of Products

Daiichi Sankyo has a
comprehensive portfolio of drugs offering a wide range of treatments for patients in a number of disease
categories including hypertension, heart disease and hyperlipidemia/atherosclerosis.

The discovery of epinephrine (also known as adrenaline) in 1889, to the development of the statin class of lipid-lowering agents and the development of the first glitazone, which revolutionized long-term control of type 2 diabetes.

New ideas and pairing of existing information with novel concepts, led to the  creation of  medicines as well as new methods of drug discovery and delivery.

Daiichi Sankyo products for hypertension, heart disease and hyperlipidemia/atherosclerosis which are currently marketed in the U.S. include several drug combinations for Cardiovascular disease.

http://dsi.com/c/document_library/get_file?uuid=5b356194-9d74-47ba-94a6-a82a7ea694cb&groupId=12065

TRIBENZOR is a Daiichi Sankyo’s product- ARB and Calcium Channel Blocker and Diuretic

How TRIBENZOR work

Tribenzor contains olmesartan medoxomil, amlodipine and hydrochlorothiazide. High blood pressure makes the heart work harder to pump blood through the body and causes damage to blood vessels. TRIBENZOR can help your blood vessels relax and reduce the amount of fluid in your blood. This can make your blood pressure lower. Medicines that lower blood pressure may lower your chance of having a stroke or a heart attack.

Some people may need more than 1—or even more than 2—medicines to help control their blood pressure. TRIBENZOR combines 3 effective medicines in 1 convenient pill. Read the following chart to learn how each medicine works in its own way to help lower blood pressure.

TRIBENZOR: 3 effective medicines in 1 pill

The medicine in TRIBENZOR How it works What it does
Angiotensin II receptor blocker Blocks a natural chemical in your body that causes blood vessels to narrow.

Lowers

Yours

blood

pressure

Calcium channel blocker Blocks the narrowing effect of calcium on your blood vessels. This helps your blood vessels relax.
Diuretic (water pill) Helps your kidneys flush extra fluid and salt from your body. This lowers the amount of fluid in your blood.

http://www.tribenzor.com/how_works.html

            Effectively lower blood pressure. People taking the 3 medicines in TRIBENZOR had greater reductions in blood pressure than did people taking any 2 of the medicines combined

            Start to work quickly. People taking TRIBENZOR saw results in as little as 2 weeks

AZOR is a Daiichi Sankyo’s product- ARB and Calcium Channel Blocker

How AZOR work

AZOR relaxes and widens blood vessels to help lower blood pressure.

You may have already tried another blood pressure medicine that works a certain way to lower blood pressure. But 1 blood pressure medicine may not be enough for you. You may find the help you need with the 2 effective medicines in AZOR.

AZOR combines 2 effective medicines in 1 convenient pill.

Learn how each medicine in AZOR works in its own way to help lower blood pressure.

The medicine in AZOR How it works What it does
Angiotensin II receptor blocker (ARB) Blocks a natural chemical in your body that causes blood vessels to narrow. This helps your blood vessels relax and widen.

Lowers

Your

Blood

pressure

Calcium channel blocker Blocks the narrowing effect of calcium on your blood vessels. This helps your blood vessels relax.

http://www.AZOR.com/how_works.html

 

Benicar and Benicar HCT are Daiichi Sankyo’s products an ARBs and Diuretics

How Benicar and Benicar HCT work

Benicar and Benicar HCT are prescription medicines used to lower high blood pressure (hypertension). They may be used alone or with other medicines used to treat high blood pressure. Benicar HCT is not for use as the first medicine to treat your high blood pressure.

 Lowering blood pressure with Benicar or Benicar HCT

There are many different choices to treat high blood pressure. You may have started with some lifestyle changes or different medicines to find what works for you. You and your doctor can talk about whether Benicar or Benicar HCT is a good choice for you.

The medicine in Benicar How it works

What it does

Angiotensin II receptor blocker (ARB) Blocks a natural chemical in the body that causes blood vessels to narrow. This helps the blood vessels relax and widen.

Lowers

your

blood

pressure

Some people may need more than 1 medicine to help manage high blood pressure. So doctors may choose to prescribe Benicar HCT. The 2 medicines in Benicar HCT help to lower blood pressure more than taking either medicine alone. You and your doctor can talk about what’s right for you.

The medicines in Benicar HCT How it works

What it does

Angiotensin II receptor blocker (ARB) Blocks a natural chemical in the body that causes blood vessels to narrow. This helps the blood vessels relax and widen.

Lowers

your

blood

pressure

Diuretic(a water pill) Helps your kidneys flush extra fluid and salt from your body. This lowers the amount of fluid in your blood.

Benicar and Benicar HCT are medicines that both

Block calcium

Block a chemical called angiotensin II

Block water and salt

There are no generic forms of Benicar or Benicar HCT

http://www.benicar.com/how_work.html

Risk of Antihypertensive drugs

Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study

BMJ 2012;344:d8190

Compatible with their urate lowering properties, calcium channel blockers and losartan are associated with a lower risk of incident gout among people with hypertension. By contrast, diuretics, β blockers, angiotensin converting enzyme inhibitors, and non-losartan angiotensin II receptor blockers are associated with an increased risk of gout.

http://www.bmj.com/content/344/bmj.d8190

Affordability of the Combination Medication for Hypertension from the Daiichi Sankyo’s product portfolio is supported by a Manufacturer Program to 2016.

There are no generic drugs for the Combination Medication for Hypertension from the Daiichi Sankyo’s product portfolio. Daiichi Sankyo, Inc., will cover up to $140 of the co-pay for BENICAR, BENICAR HCT, AZOR, and TRIBENZOR after the patient pays the first $25. Offer applies to patients with commercial insurance; $25 initial savings available for patients without insurance; offer expires 2016. If a retail or mail-order pharmacy does not accept the Savings That Last card, patients may obtain a Direct Member Reimbursement form by calling the number on the back of the card to receive instructions on how to obtain the savings benefit. Offer not valid for patients enrolled in a state or federal healthcare program including but not limited to Medicaid, Medicare, Veterans Administration, or TRICARE/CHAMPUS. Offer valid in the United States and Puerto Rico. Void where taxed, restricted, or prohibited by law. Void in Massachusetts, except for patients without insurance. Daiichi Sankyo, Inc., reserves the right to rescind, revoke, or amend this program, at any time, without notice.

 TRIBENZOR is preferred on some of the largest Medicare Part D plans.

http://www.tribenzorhcp.com/savings_that_last.html

Cost Savings Associated with Filling a 3-Month Supply of Prescription Medicines

http://ideas.repec.org/a/wkh/aheahp/v7y2009i4p255-264.html

 Out-of-pocket and Total Costs of Fixed-dose Combination Antihypertensives and Their Components

Atonu Rabbani1 and G. Caleb Alexander1,2,3,4

American Journal of Hypertension (2008); 21, 5, 509–513. doi:10.1038/ajh.2008.31

Given patient burden and non-adherence from out-of-pocket prescription costs, the clinical benefits of brand-named fixed-dose combination antihypertensive therapy should be balanced with their greater out-of-pocket costs.

http://www.nature.com/ajh/journal/v21/n5/abs/ajh200831a.html

 

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