Advertisements
Feeds:
Posts
Comments

Posts Tagged ‘Stroke’


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

Aspirin-clopidogrel combination no better than aspirin alone.

Antiplatelet drugs such as aspirin are routinely prescribed to help prevent new strokes in people with a history of lacunar stroke.  The Secondary Prevention of Small Subcortical Strokes (SPS3) trial was designed to determine if adding clopidogrel to aspirin would offer better protection than aspirin alone.  The results appear in the Aug. 30th New England Journal of Medicine.*  They show that the aspirin-clopidogrel combination was about equal to aspirin in reducing the risk of any type of stroke, but it almost doubled the risk of gastrointestinal bleeding.

“For all stroke therapeutics, there is a need to balance the potential benefits against the risks.  The SPS3 findings establish that for lacunar stroke, dual therapy with aspirin and clopidogrel carries significant risk and minimal benefit,” said Walter Koroshetz, M.D., deputy director of National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

The SPS3 trial is funded by NINDS and led by Oscar R. Benavente, M.D., research director of the Stroke and Cerebrovascular Health program at the University of British Columbia in Vancouver, British Columbia.

In addition to comparing dual antiplatelet therapy with aspirin, the trial was designed to test two levels of blood pressure control.  After an interim data analysis in August 2011, the antiplatelet component of the trial was stopped.  NIH also issued a clinical alert, warning that there was “little likelihood of benefit in favor of aspirin plus clopidogrel [for] recurrent stroke should the study continue to conclusion.”  The blood pressure component of the trial is ongoing, and the trial participants have been encouraged to continue taking aspirin without clopidogrel.

Strokes occur when blood vessels that supply the brain rupture or become blocked, such as by a blood clot.   Antiplatelet drugs interfere with the formation of blood clots.

Lacunar strokes occur due to chronic high blood pressure, which in turn leads to progressive narrowing and finally blockage of small arteries that supply deep brain structures.   They account for up to one-fifth of all strokes and are especially common among African-Americans, Hispanics and people with diabetes.  Although lacunar strokes tend to produce relatively small lesions, they can cause disability depending on where they occur in the brain.

The SPS3 trial involves more than 3,000 participants at 82 clinical centers in North and South America and in Spain.  The participants are age 30 and older, and all had a recent history of lacunar stroke prior to enrollment.  About 52 percent are white, 31 percent Hispanic and 17 percent black.

For the antiplatelet component of the trial, about half of the participants received 325 milligrams of aspirin and 75 milligrams of clopidogrel daily, and the other half received aspirin and placebo.  The participants were also randomly assigned to receive either standard control of systolic blood pressure (less than 130 mm Hg) or aggressive control (130-149 mm Hg).

After eight years of study, the annual risk of recurrent stroke was 2.7 percent in the aspirin-only group and 2.5 percent in the aspirin plus clopidogrel group.  Most of the recurrent strokes in both groups were lacunar strokes.  The rate of serious or life-threatening internal bleeding was 1.1 percent in the aspirin group and 2.1 percent in the dual therapy group.  The difference was due mostly to a higher number of gastrointestinal bleeds in the dual therapy group.  The percentage of brain bleeds in the two groups was not significantly different.  Deaths from any cause were also higher in the aspirin-clopidogrel group.

For both groups, stroke recurrence was lower than the investigators had expected.  When the SPS3 trial began in 2003, another large trial that tested warfarin vs. aspirin for stroke prevention had just ended.  Warfarin is an anticoagulant, another class of drugs that interferes with blood clotting.  That trial, called the Warfarin vs. Aspirin Recurrent Stroke Study (WARSS), found that patients with a history of lacunar strokes who took aspirin had an annual stroke recurrence rate of about 7 percent.  (Warfarin and aspirin were about equal.)

This reflects a common trend, Dr. Benavente said.  “What we see more and more often in stroke prevention trials is a significant decrease in stroke risk, compared to data from 10 years ago.  We have better medications now to control stroke risk factors such as high blood pressure and cholesterol, and these are clearly having an impact.”

In prior studies, antiplatelet drugs including aspirin or clopidogrel alone, or a combination of aspirin and dipyridamole, have been shown to reduce stroke risk in patients with heart disease or prior stroke.  In one trial, aspirin combined with clopidogrel was more effective than aspirin alone at reducing stroke risk in patients with atrial fibrillation, a type of abnormal heart rhythm.  However, other trials involving broader stroke populations found no added benefit from combining aspirin and clopidogrel.  Therefore, current practice guidelines recommend aspirin alone, clopidogrel alone, or aspirin plus dipyridamole for secondary prevention after most types of stroke.  The SPS3 results are consistent with those guidelines.

Researchers continue to investigate whether the clopidogrel-aspirin combination might be beneficial for patients with other types of stroke, such as transient ischemic attack (TIA).  This is a type of stroke in which symptoms fade away in less than 24 hours; it is also a warning that a more damaging stroke may be imminent.  The Platelet-Oriented Inhibition in New TIA (POINT) trial is testing whether aspirin plus clopidogrel are effective at preventing major strokes when given within 12 hours of a TIA.  That trial is also funded by NINDS.

Source

http://www.ninds.nih.gov/news_and_events/news_articles/SPS3_antiplatelet_results.htm

Related research topics are addressing this topic:

Commonly-used-painkillers-may-protect-against-skin-cancer

Atrial-fibrillation-the-latest-management-strategies

Cardiovascular-disease-cvd-and-the-role-of-agent-alternatives-in-endothelial-nitric-oxide-synthase-enos-activation-and-nitric-oxide-production

Role-of-viral-infection-in-prostate-cancer

Guidelines-updated-for-unstable-anginanon-st-elevation-myocardial-infarction

Stroke-ten-big-factors-heart-rate-no-predictor-of-second-stroke

Outcomes-in-high-cardiovascular-risk-patients-prasugrel-effient-vs-clopidogrel-plavix-aliskiren-tekturna-added-to-ace-or-added-to-arb

Stroke-and-bleeding-in-atrial-fibrillation-with-chronic-kidney-disease

Coronary-artery-disease-medical-devices-solutions-from-first-in-man-stent-implantation-via-medical-ethical-dilemmas-to-drug-eluting-stents

Aspirin a day tied to lower cancer mortality

Assessing-drug-risks-on-perspective

Gaps-tensions-and-conflicts-in-the-fda-approval-process-implications-for-clinical-practice

Predicting-potential-cardiac-events

Nitrit oxide-and-platelet-aggregation

Coronary-artery-disease-medical-devices-solutions-from-first-in-man-stent-implantation-via-medical-ethical-dilemmas-to-drug-eluting-stents

University-of-florida-to-genotype-all-comers-at-cath-lab-to-personalize-treatment-with-plavix-eventually-other-drugs

Advertisements

Read Full Post »


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

Leg compressions may enhance stroke recovery:

Successive, vigorous bouts of leg compression s following a stroke appear to trigger natural protective mechanisms that reduce damage. Make use of the blood pressure cuff in the emergencies for the same.

Compressing then releasing the leg for several five-minute intervals used in conjunction with the clot-buster tPA, essentially doubles efficacy, said Dr. David Hess, a stroke specialist who chairs the Medical College of Georgia Department of Neurology at Georgia Health Sciences University. “This is potentially a very cheap, usable and safe – other than the temporary discomfort – therapy for stroke,” said Hess, an author of the study in the journal Stroke. The compressions can be administered with a blood pressure cuff in the emergency room during preparation for tPA, or tissue plasminogen activator, currently the only Food and Drug Administration-approved stroke therapy.

“Much like preparation to run a marathon, you are getting yourself ready, you are conditioning your body to survive a stroke,” Hess said of a technique that could also be used in an ambulance or at a small, rural hospital. For the studies Dr. Nasrul Hoda, an MCG research scientist and the study’s corresponding author, developed an animal model with a clot in the internal carotid artery, the most common cause of stroke. The compression technique called remote ischemic perconditioning – “per” meaning “during” –reduced stroke size in the animals by 25.7 percent, slightly better than tPA’s results. Together, the therapies reduced stroke size by 50 percent and expanded the treatment window during which tPA is safe and effective.

Next steps include looking for biomarkers that will enable researchers to easily measure effectiveness in humans, Hess said. One marker may be increased blood flow to the brain, which occurred in the treated animals.

The first clinical trial likely will include putting a blood pressure cuff on the legs of a small number of stroke patients to see if the finding holds. The researchers also have plans to analyze the blood of healthy individuals, before and after compression, seeking mediators that stand out as clear markers of change. They also want to go back to the animal model to see if applying the technique after giving tPA works even better. Clinical evidence already suggests that remote ischemic perconditioning can aid heart attack recovery, including a 2010 study in the journal Lancet in which the technique, used in conjunction with angioplasty to intervene in a heart attack, reduced heart damage. Nature seems to support it as well since people who experience short periods of inadequate blood flow – angina in the case of heart disease and transient ischemic attacks in the brain – before having a major event tend to recover better than patients who have a full-blown stroke or heart attack out of the blue.

“Small episodes of ischemia seem to protect our organs – not just our brains – from major ischemia,” said Hess, although the researchers are just starting to learn why. Theories include that leg muscles, in response to the temporary loss of blood and oxygen, somehow stimulate nerves to protect the brain and/or that the muscles themselves release the protection.

They also suspect the vagus nerve, which delivers information to the brain about how other organs are doing and helps regulate inflammation, is a player.

Read more at: http://medicalxpress.com/news/2012-08-leg-compressions-recovery.html#jCp

Read Full Post »


 

Reporter: Aviva Lev-Ari, PhD, RN

Big 10 Risk Factors for Stroke

It’s clear that strokes are a major cause of disability and death throughout the world. But many of the prime risk factors for stroke are within your power to change — something we have long known. A large international study published in the Lancet underscored how far prevention efforts could go. Collecting data from stroke patients and healthy individuals in 22 countries, it found that 10 largely modifiable risk factors account for 90 percent of the risk of stroke worldwide. That means there is much you can do to rein in your personal risk. Here are the Big 10: 

1. High blood pressure. This is the biggest contributor to strokes worldwide. The Lancet study estimated that blood pressure readings of 160/90 mm Hg or higher accounted for up to 52 percent of the “population-attributable risk” of stroke.

2. Sedentary lifestyle. In general, regular exercise is a good move for your cardiovascular health, as it helps lower blood pressure, regulate your weight, boost “good” high-density lipoprotein (HDL) cholesterol and prevent or manage type 2 diabetes. And there’s evidence that even moderate levels of physical activity can curb your risk of stroke.

3. Being “apple-shaped.” We often talk about excess pounds being a risk to your cardiovascular health, but it’s that middle-aged spread around the waist that may be particularly worrisome.

4. Smoking. If you are still a smoker, you need to work on quitting. In the Lancet study, there was no evidence that former smokers were at greater risk of stroke than people who’d never smoked — suggesting that the excess risk declines quickly after you quit.

5. Diet. Diet may be just as important as smoking habits. In particular, the Lancet study found, features of the traditional Mediterranean diet — namely, a high intake of fish and fruit — appeared protective against stroke.

6. Atrial fibrillation. This is the most common form of heart-rhythm disturbance, in which the upper chambers of the heart (atria) do not contract in a rhythmic pattern but instead quiver chaotically. If you have atrial fibrillation, it is critical that you take any anti-clotting medication or other drugs that your doctor has prescribed.

7. Cholesterol. Studies suggest that the relationship between cholesterol and stroke risk is complex. In theLancet study, total cholesterol levels were not associated with strokes, confirming epidemiological evidence, but higher levels of high-density lipoprotein (HDL, or “good”) cholesterol were linked to a lower risk of ischemic stroke.

8. Alcohol. Moderate drinking of alcohol was linked to a reduced risk of ischemic stroke, while any amount more than that was connected to an increased risk versus teetotaling.

9 & 10. Stress and depression. Both chronic stress (related to home or work life) and depression symptoms were linked to an increased risk of stroke. It’s not completely clear why; it could be because mental-health woes make it more difficult to stick to your healthy diet, exercise and medication regimen. Also unclear is whether depression therapy or stress-management classes can help lower your stroke risk.

Takeaway. The overall message here is that there are many steps you can take to help ward off a stroke. If you are not sure which of these risk factors apply to you or what you should be doing about them, talk with your doctor. It could make a substantial difference in the long run.

Posted in Hypertension and Stroke on August 7, 2012

ESC: Heart Rate No Predictor of Second Stroke

By Chris Kaiser, Cardiology Editor,MedPage Today

Published: August 27, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

MUNICH — In patients who had a stroke, a high resting heart rate was not associated with recurrent stroke, but was associated with cognitive and functional decline, according to a pooled analysis of the PRoFESS study.

Of the 20,165 patients evaluated, a high baseline heart rate — 77 bpm and greater — was not significantly associated with recurrent stroke or myocardial infarction (MI) compared with lower heart rates, reported Michael Böhm, MD, of the University of Saarland in Saar, Germany, and colleagues.

However, in patients with a recurrent stroke (n=1,627), a high heart rate had a negative impact on patients’ global disability scale according to the modified Rankin score at baseline and 3 months after the recurrent stroke, Böhm reported here at the European Society of Cardiology (ESC) meeting.

In addition, more patients with high heart rates had Mini-Mental State Examination (MMSE) scores indicative of a greater degree of cognitive decline (≤24) at 1 and 3 months (both were significant atP<0.0001), Böhm said.

“What is most striking is that at 3 months, 15% of those with a heart rate of 77 bpm or greater had signs of dementia,” he said during his presentation.

“This study is a landmark analysis and fills a major knowledge gap,” said study discussant Jeffrey Borer, MD, of SUNY Downstate Medical Center in Brooklyn.

“That heart rate doesn’t predict recurrent stroke, but does predict cognitive decline is a new finding,” he said.

He added that many studies have been conducted looking at heart rate, but none of them involved data because of a stroke. “Whether we can affect outcomes by lowering heart rate is not known and should be the next step in this research,” he said.

The initial PRoFESS (Prevention Regimen for Effectively Avoiding Second Stroke) trial found no evidence that aspirin and extended release dipyridamole were superior to clopidogrel (Plavix) or that telmisartan was superior to placebo to prevent recurrent stroke.

In this post hoc analysis, Böhm and colleagues included 20,165 patients enrolled from 35 countries. They were separated by heart rates, with the top three quintiles representing 71-76 bpm, 77-82 bpm and 82 or more bpm, respectively.

The mean age was 66 and less than half (36%) were women. Those with high heart rates tended to be younger, women, and less likely to drink or smoke.

They also tended to have more large cerebral artery involvement and higher baseline modified Rankin scores and NIH Stroke Scale scores, as well as worse baseline scores for self-care. In addition, there were fewer of them who took protective medications such as beta blockers, statins, and diuretics, Böhm said.

Compared with the lowest quintile, those in the top two quintiles had an increased risk of all-cause death (HR 1.42 and 174, respectively). The difference was significant at P<0.0001.

Patients in the top three quintiles were at an increased risk cardiovascular death (HR 1.39 for the third quintile, P<0.0001) and those in the fifth quintile had an increased risk for non-cardiovascular death (HR 1.66, P=0.0016).

“These findings identify a high-risk group of patients starting at a heart rate of 71 bpm that will die primarily from cardiovascular events,” Böhm said.

Surprisingly, heart rate did not affect the risk for recurrent stroke, MI, or new or worsening heart failure.

Even when researchers included blood pressure in the adjusted analysis, they found no change of risk, “indicating that the effects of heart rate on risk are independent of the blood pressure,” they wrote in the European Heart Journal, which published the study to coincide with the ESC meeting.

The study is limited because it relied only on baseline heart rate measurement, and perhaps variations in heart rate during the trial could explain the failure to predict strokes, Borer said.

Böhm also noted that the study is limited because it is a retrospective post hoc analyses of a randomized trial that did not randomize according to heart rate.

The PRoFESS study was funded by Boehringer Ingelheim.

Böhm reported relationships with AstraZeneca, Bayer AG, Boehringer Ingelheim, Novartis, Pfizer, sanofi-aventis, Servier, Adrian-Medtronic, Daiichi-Sankyo, MSD, AWD Dresden, and Berlin-Chemie. One co-author reported relationships with Boehringer Ingelheim, Lundbeck, Mitsubishi, Phagenesi, and ReNeuron. All other authors reported no conflicts of interest.

Borer reported a relationship with Servier.

 

Read Full Post »


 

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

A new proof-of-concept study shows that plasma concentrations of precursor fragments of the neuropeptide enkephalin (proenkephalin A, or PENK-A) are elevated in patients with acute stroke compared with those with TIA and nonischemic events.

Researchers are making efforts to investigate neuropeptides in patients presenting with symptoms of acute cerebrovascular disease.

Although the mature neuropeptides are degraded within minutes, their precursor fragments are much more stable and represent neuropeptide synthesis in stoichiometric relations. “They are therefore well suited as biomarkers and may be suitable for measurement in clinical settings,” said Dr. Doehner.

The precursor neuropeptides proenkephalin A (PENK-A) and protachykinin (PTA) are markers of blood-brain barrier integrity and have been recently discussed in vascular dementia and neuroinflammatory disorders.

{Ernst  A., Kohrle  J., Bergmann  A.;  Proenkephalin A 119—159, a stable proenkephalin. A precursor fragment identified in human circulation, Peptides 27 2006 1835-1840
Ernst  A., Suhr  J., Kohrle  J., Bergmann  A.;  Detection of stable N-terminal protachykinin A immunoreactivity in human plasma and cerebrospinal fluid, Peptides 29 2008 1201-1206}

Researchers are making efforts to use these precursor fragments as markers to distinguish an ischemic stroke from a transient ischemic attack (TIA) or an intracerebral hemorrhage.

The authors strongly hope that it may help to advance the use of biomarkers in the clinical evaluation of stroke patients.

Despite the limitations, elevated PENK-A levels correlated with stroke severity and with brain lesion size, and they predicted mortality and more functional disability.

“There is clearly an unmet need to establish biomarker-guided prognostic and functional evaluations for patients with stroke, said the lead author Wolfram Doehner, MD, PhD, from the Center for Stroke Research, in Berlin, Germany

The new report was published in Journal of the American College of Cardiology.

http://content.onlinejacc.org/article.aspx?articleid=1217869

http://www.medscape.com/viewarticle/768457?src=nldne

 

 

 

 

Read Full Post »


Percutaneous Transluminal Angioplasty and Stenting (PTAS) – Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis

Reporter: Aviva Lev-Ari, PhD, RN

 

RESULTS

Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (Original Article, N Engl J Med 2011 ; 365 : 993 – 1003) . In the first paragraph of Results (page 996), the penultimate sentence should have read, “Of the 224 patients in the PTAS group, 16 (7.1%) did not have a stent placed (the procedure was not performed in 4 patients, the procedure was aborted before the lesion was accessed in 7, and angioplasty alone was performed in 5),”

http://www.nejm.org/doi/full/10.1056/NEJMx120039?query=TOC

BACKGROUND

Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial.

METHODS

We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days.

CONCLUSIONS

In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected.

http://www.nejm.org/doi/full/10.1056/nejmoa1105335

Read Full Post »

« Newer Posts