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Archive for the ‘inflammation independent of lipid levels’ Category


The role of PET/CT in diagnosing giant cell arteritis (GCA) and assessing the risk of ischemic events

 

Reporter: Aviva Lev-Ari, PhD, RN

 

 

May 20, 2019 — PET/CT images are offering evidence of a link between vascular patterns at the time of diagnosis for giant cell arteritis (GCA) and a patient’s risk of an ischemic event, Spanish researchers explained in a study published online on 12 May in the European Journal of Nuclear Medicine and Molecular Imaging.

The group found that patients with inflammation in vertebral arteries, which causes blood vessels to narrow, were five times more likely to develop ischemic symptoms. The information may be particularly helpful because GCA is difficult to diagnose in its early stages.

“Bearing in mind these results and our findings, we consider that the vertebral arteries should be carefully studied in patients with suspected GCA, not only to support the diagnosis but also to assess the risk of development of ischemic events,” wrote lead author Dr. Jaume Mestre-Torres and colleagues from Hospital Vall d’Hebron in Barcelona.

GCA’s challenges

Giant cell arteritis is an inflammatory disease that causes the large blood vessels to narrow and restrict blood flow. The affliction is typically seen in the temporal arteries and the aorta in adults older than 50. Currently, there is little information on how the disease develops, although there are indications that it may be linked to genetics.

The challenge for clinicians is that there are “no specific clinical symptoms that lead to the diagnosis of GCA, but headache and ischemic symptoms such as jaw claudication and transient visual loss or permanent visual loss may raise suspicion [of the disease],” the authors noted.

Results

In assessing visual loss, the team found no significant differences between patients with vertebral artery involvement and permanent visual loss (61.5%) and patients with vertebral artery issues and no permanent visual loss (58.8%) (p = 0.88). Interestingly, the presence of intrathoracic large-vessel vasculitis tended to protect against a patient’s likelihood of permanent visual loss.

In addition, “all patients with vertebral involvement but no aortic involvement showed ischemic manifestations at disease onset,” the researchers noted. “In contrast, none of the patients with aortic involvement but no vertebral hypermetabolism showed ischemic symptoms.”

SOURCE

https://www.auntminnieeurope.com/index.aspx?sec=sup&sub=mol&pag=dis&ItemID=617395

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@Cleveland Clinic – Serial measurements of high-sensitivity C-reactive protein (hsCRP) post acute coronary syndrome (ACS) may help identify patients at higher risk for morbidity and mortality

 

Reporter: Aviva Lev-Ari, PhD, RN

 

Original Investigation
March 6, 2019

Association of Initial and Serial C-Reactive Protein Levels With Adverse Cardiovascular Events and Death After Acute Coronary Syndrome, A Secondary Analysis of the VISTA-16 Trial

Key Points

Question  Are initial and serial increases in high-sensitivity C-reactive protein levels after acute coronary syndrome in medically optimized patients associated with increased risk of a major cardiac event, cardiovascular death, and all-cause death?

Findings  In this secondary analysis of the VISTA-16 randomized clinical trial that included 5145 patients, baseline and longitudinal high-sensitivity C-reactive protein levels were independently associated with increased risk of a major adverse cardiac event, cardiovascular death, and all-cause death during the 16-week follow-up.

Meaning  Monitoring high-sensitivity C-reactive protein levels in patients after acute coronary syndrome may help better identify patients at greater risk for recurrent cardiovascular events or death.

Abstract

Importance  Higher baseline high-sensitivity C-reactive protein (hsCRP) levels after an acute coronary syndrome (ACS) are associated with adverse cardiovascular outcomes. The usefulness of serial hsCRP measurements for risk stratifying patients after ACS is not well characterized.

Objective  To assess whether longitudinal increases in hsCRP measurements during the 16 weeks after ACS are independently associated with a greater risk of a major adverse cardiac event (MACE), all-cause death, and cardiovascular death.

Results  Among 4257 patients in this study, 3141 (73.8%) were men and the mean age was 60.3 years (interquartile range [IQR], 53.5-67.8 years). The median 16-week low-density lipoprotein cholesterol level was 64.9 mg/dL (IQR, 50.3-82.3 mg/dL), and the median hsCRP level was 2.4 mg/L (IQR, 1.1-5.2 mg/L). On multivariable analysis, higher baseline hsCRP level (hazard ratio [HR], 1.36 [95% CI, 1.13-1.63]; P = .001) and higher longitudinal hsCRP level (HR, 1.15 [95% CI, 1.09-1.21]; P < .001) were independently associated with MACE. Similar significant and independent associations were shown between baseline and longitudinal hsCRP levels and cardiovascular death (baseline: HR, 1.61 per SD [95% CI, 1.07-2.41], P = .02; longitudinal: HR, 1.26 per SD [95% CI, 1.19-1.34], P < .001) and between baseline and longitudinal hsCRP levels and all-cause death (baseline: HR, 1.58 per SD [95% CI, 1.07-2.35], P = .02; longitudinal: HR, 1.25 per SD [95% CI, 1.18-1.32], P < .001).

Conclusions and Relevance  Initial and subsequent increases in hsCRP levels during 16 weeks after ACS were associated with a greater risk of the combined MACE end point, cardiovascular death, and all-cause death despite established background therapies. Serial measurements of hsCRP during clinical follow-up after ACS may help to identify patients at higher risk for mortality and morbidity.

SOURCE

https://jamanetwork.com/journals/jamacardiology/fullarticle/2725734

 

Inflammation’s role in residual risk

Residual risk of cardiovascular events or death remains high following ACS, despite coronary revascularization and optimal guideline-directed treatment with antiplatelet and LDL cholesterol-lowering agents. Inflammation is thought to drive this risk, but no effective treatment for such inflammation is commercially available. The secretory phospholipase A2 inhibitor varespladib was developed to meet this need, and it was evaluated in VISTA-16.

VISTA-16 was an international, multicenter clinical trial that randomized 5,145 patients in a double-blind manner to varespladib or placebo on a background of atorvastatin treatment within 96 hours of presentation with ACS. The trial was terminated early due to futility and likely harm from the drug, which was subsequently pulled from development.

Implications for practice

The association of increasing CRP levels with residual cardiovascular risk may prompt more intensive treatment to lower this risk. In particular, a secondary analysis showed that use of antiplatelet agents (clopidogrel, ticlopidine and prasugrel) was associated with stable or decreasing hsCRP levels.

“Monitoring not only lipids but also hsCRP after ACS may help us better identify patients at increased risk for recurrent cardiovascular events or death,” notes Dr. Puri. “High or increasing CRP levels could be an indication to optimize dual antiplatelet therapy post-ACS, along with high-intensity statin therapy (and possibly PCSK9 inhibitors) and antihypertensive therapy, in addition to instituting measures that are globally beneficial, such as dietary modifications and cardiac rehabilitation/exercise.”

SOURCE

https://consultqd.clevelandclinic.org/increasing-inflammation-correlates-with-residual-risk-after-acute-coronary-syndrome/amp/?__twitter_impression=true

 

Other related articles published in this Open Access Online Scientific Journal, include the following:

 

Biomarkers and risk factors for cardiovascular events, endothelial dysfunction, and thromboembolic complications

Larry H Bernstein, MD, FCAP, Curator

https://pharmaceuticalintelligence.com/2014/09/09/biomarkers-and-risk-factors-for-cardiovascular-events-endothelial-dysfunction-and-thromboembolic-complications/

 

A Concise Review of Cardiovascular Biomarkers of Hypertension

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/04/25/a-concise-review-of-cardiovascular-biomarkers-of-hypertension/

 

Acute Coronary Syndrome (ACS): Strategies in Anticoagulant Selection: Diagnostics Approaches – Genetic Testing Aids vs. Biomarkers (Troponin types and BNP)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/03/13/acute-coronary-syndrome-acs-strategies-in-anticoagulant-selection-diagnostics-approaches-genetic-testing-aids-vs-biomarkers-troponin-types-and-bnp/

 

In Europe, BigData@Heart aim to improve patient outcomes and reduce societal burden of atrial fibrillation (AF), heart failure (HF) and acute coronary syndrome (ACS).

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/10/in-europe-bigdataheart-aim-to-improve-patient-outcomes-and-reduce-societal-burden-of-atrial-fibrillation-af-heart-failure-hf-and-acute-coronary-syndrome-acs/

 

Cardiovascular Diseases and Pharmacological Therapy: Curations by Aviva Lev-Ari, PhD, RN, 2006 – 4/2018

https://pharmaceuticalintelligence.com/2014/04/17/cardiovascular-diseases-and-pharmacological-therapy-curations-by-aviva-lev-ari-phd-rn/

 

 

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Paraoxonase 2 (PON2) appears to play a cardioprotective role in both human and experimental heart failure: Cardiologist Wai Hong Wilson Tang, MD, Director of Cleveland Clinic Lerner Research Institute’s Center for Clinical Genomics.

Reporter: Aviva Lev-Ari, PhD, RN

Enzyme Protects Heart Against Stress and Could Potentially Lead to New Heart Failure Treatments

https://consultqd.clevelandclinic.org/enzyme-protects-heart-against-stress-and-could-potentially-lead-to-new-heart-failure-treatments/amp/?__twitter_impression=true

Original Study:
 2018 Jun;121:117-126. doi: 10.1016/j.freeradbiomed.2018.04.583. Epub 2018 May 2.

Paraoxonase 2 prevents the development of heart failure.

Abstract

BACKGROUND:

Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression.

METHODS AND RESULTS:

Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression. To determine the cardiac-specific function of PON2, we performed heart transplantations in which PON2-def and wild type (WT) donor hearts were implanted into WT recipient mice. Beating scores of the donor hearts, assessed at 4 weeks post-transplantation, were significantly decreased in PON2-def hearts when compared to WT donor hearts. By using a transverse aortic constriction (TAC) model, we found PON2 deficiency significantly exacerbated left ventricular remodeling and cardiac fibrosis post-TAC. We further demonstrated PON2 deficiency significantly enhanced ROS generation in heart tissues post-TAC. ROS generation was measured through dihydroethidium (DHE) using high-pressure liquid chromatography (HPLC) with a fluorescent detector. By using neonatal cardiomyocytes treated with CoCl2 to mimic hypoxia, we found PON2 deficiency dramatically increased ROS generation in the cardiomyocytes upon CoCl2 treatment. In response to a short CoCl2 exposure, cell viability and succinate dehydrogenase (SDH) activity assessed by MTT assay were significantly diminished in PON2-def cardiomyocytes compared to those in WT cardiomyocytes. PON2-def cardiomyocytes also had lower baseline SDH activity. By using adult mouse cardiomyocytes and mitochondrial ToxGlo assay, we found impaired cellular ATP generation in PON2-def cells compared to that in WT cells, suggesting that PON2 is necessary for proper mitochondrial function.

CONCLUSION:

Our study suggests a cardioprotective role for PON2 in both experimental and human heart failure, which may be associated with the ability of PON2 to improve mitochondrial function and diminish ROS generation.

KEYWORDS:

Cardiomyopathy; Heart failure; Paraoxonase 2

PMID:
29729330
PMCID:
PMC5971153
 [Available on 2019-06-01]
DOI:
10.1016/j.freeradbiomed.2018.04.583

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The Promise of Low-Dose Aspirin on Longevity in the Geriatric Population: No Effect on Outcomes in the US and Australia

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 10/17/2018

https://www.nejm.org/doi/full/10.1056/NEJMoa1800722

Effect of Aspirin on Disability-free Survival in the Elderly

ORIGINAL ARTICLE

Effect of Aspirin on Disability-free Survival in the Healthy Elderly

J.J. McNeil and Others

    

McNeil et al. conducted the randomized, placebo-controlled Aspirin in Reducing Events in the Elderly (ASPREE) trial to investigate whether the daily use of aspirin, at a dose of 100 mg, in healthy, community-dwelling older adults would prolong a healthy life span, free from dementia and persistent physical disability. Trial participants were community-dwelling men and women from Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States).

Clinical Pearls

  Is there any evidence to support the use of aspirin for primary prevention of cardiovascular or other chronic disease in healthy older adults?

Several large, randomized trials have shown the efficacy of aspirin for the secondary prevention of cardiovascular disease among persons with a history of coronary heart disease or stroke. The evidence supporting a benefit of aspirin therapy in the primary prevention of cardiovascular or other chronic disease is less conclusive despite favorable trends suggesting that aspirin use reduces the incidence of cardiovascular events and possibly reduces the incidence of cancer and cancer-related mortality, particularly from colorectal cancer.

  Does the daily use of 100 mg of aspirin prolong a healthy lifespan in older adults without cardiovascular disease, dementia, or physical disability?

In the ASPREE trial, the daily use of 100 mg of enteric-coated aspirin did not differ significantly from placebo in influencing the rates of disability-free survival at a median of 4.7 years. The primary end point of death, dementia, or physical disability occurred in 921 participants in the aspirin group (21.5 events per 1000 person-years) and in 914 in the placebo group (21.2 events per 1000 person-years). The between-group difference was not significant (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). Among participants who had a primary end-point event, death was the most common first event (in 911 participants [50% of the events] at a mean age of 77.5 years), dementia was the next most common (in 549 participants [30% of the events] at a mean age of 77.7 years), and persistent physical disability was the least common.

Morning Report Questions

Q. How does a daily aspirin dose of 100 mg influence rates of death from any cause and the risk of major hemorrhage in healthy older adults?

A. In the ASPREE trial, the secondary end point of death from any cause, denoting death as the first, second, or third event to occur in the primary end point, occurred in 558 participants in the aspirin group (12.7 events per 1000 person-years) and in 494 participants in the placebo group (11.1 events per 1000 person-years) (hazard ratio, 1.14; unadjusted 95% CI, 1.01 to 1.29). Because there was no adjustment for multiple comparisons of secondary end points, no inferences can be made regarding differences in mortality between the two groups. Major hemorrhage occurred in 3.8% of the participants in the aspirin group, as compared with 2.8% of those in the placebo group (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). Fatal or nonfatal hemorrhagic stroke (including subarachnoid hemorrhage) occurred in 49 participants (0.5%) in the aspirin group and in 40 (0.4%) in the placebo group.

Q. How generalizable are the results of the ASPREE trial?

A. White participants comprised 91% of the overall trial cohort. Owing to the small number of blacks and Hispanics (including participants who were younger than 70 years of age) and other nonwhites, the applicability of the main findings of the ASPREE trial to these subgroups is unclear.

 

Daily Low-Dose Aspirin Found to Have No Effect on Healthy Life Span in Older People?

According to 3 articles published online The New England Journal of Medicine (16 September 2018), daily low-dose aspirin was found to have no effect on healthy life span in older people. This large NIH-funded study examined outcomes in United States and Australia

Results showed that in a large clinical trial to determine the risks and benefits of daily low-dose aspirin in healthy older adults without previous cardiovascular events,

Aspirin did not prolong healthy, independent living (life free of dementia or persistent physical disability).

Risk of dying from a range of causes, including cancer and heart disease, varied and will require further analysis and additional follow-up of study participants. These initial findings from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, partially supported by the National Institutes of Health.

ASPREE is an international, randomized, double-blind, placebo-controlled trial that enrolled 19,114 older people (16,703 in Australia and 2,411 in the United States). The study began in 2010 and enrolled participants aged 70 and older; 65 was the minimum age of entry for African-American and Hispanic individuals in the United States because of their higher risk for dementia and cardiovascular disease. At study enrollment, ASPREE participants could not have dementia or a physical disability and had to be free of medical conditions requiring aspirin use. They were followed for an average of 4.7 years to determine outcomes.

In the total study population, treatment with 100 mg of low-dose aspirin per day did not affect survival free of dementia or disability. Among the people randomly assigned to take aspirin,

  • 90.3% remained alive at the end of the treatment without persistent physical disability or dementia, compared with 90.5% of those taking a placebo.
  • Rates of physical disability were similar, and rates of dementia were almost identical in both groups. However,
  • the group taking aspirin had an increased risk of death compared to the placebo group: 5.9% of participants taking aspirin and 5.2% taking placebo died during the study.

This effect of aspirin has not been noted in previous studies; and caution is needed in interpreting this finding. The higher death rate in the aspirin-treated group was due primarily to a higher rate of cancer deaths. A small increase in new cancer cases was reported in the group taking aspirin but the difference could have been due to chance. The authors also analyzed the ASPREE results to determine whether cardiovascular events took place. They found that

  • the rates for major cardiovascular events — including coronary heart disease, nonfatal heart attacks, and fatal and nonfatal ischemic stroke — were similar in the aspirin and the placebo groups. In the aspirin group, 448 people experienced cardiovascular events, compared with 474 people in the placebo group.

Significant bleeding — a known risk of regular aspirin use — was also measured. The authors noted that

  • aspirin was associated with a significantly increased risk of bleeding, primarily in the gastrointestinal tract and brain. Clinically significant bleeding — hemorrhagic stroke, bleeding in the brain, gastrointestinal hemorrhages or hemorrhages at other sites that required transfusion or hospitalization — occurred in 361 people (3.8%) on aspirin and in 265 (2.7%) taking the placebo.
  • As would be expected in an older adult population, cancer was a common cause of death, and 50% of the people who died in the trial had some type of cancer.
  • Heart disease and stroke accounted for 19% of the deaths and major bleeding for 5%.

The ASPREE team is continuing to analyze the results of this study and has implemented plans for monitoring participants. As these efforts continue, the authors emphasized that older adults should follow the advice from their own physicians about daily aspirin use. It is important to note that the new findings do not apply to people with a proven indication for aspirin such as stroke, heart attack or other cardiovascular disease. In addition, the study did not address aspirin’s effects in people younger than age 65. Also, since only 11% of participants had regularly taken low-dose aspirin prior to entering the study, the implications of ASPREE’s findings need further investigation to determine whether healthy older people who have been regularly using aspirin for disease prevention should continue or discontinue use.

SOURCE

From: OnTarget <ontarget@targethealth.com>

Date: September 23, 2018 at 10:47:06 PM EDT

To: avivalev-ari@alum.berkeley.edu

Subject: OnTarget Newsletter

 

Other 121 articles on ASPIRIN were published in this Open Access Online Scientific Journal, including the following:

https://pharmaceuticalintelligence.com/?s=Aspirin

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A new mechanism of action to attack in the treatment of coronary artery disease (CAD), Novartis developed Ilaris (canakinumab), a human monoclonal antibody targeting the interleukin-1beta innate immunity pathway

Reporter: Aviva Lev-Ari, PhD, RN

 

Speaking at an ESC press briefing, Ridker said, “This is what personalized predictive medicine is all about.” Once a patient has experienced an MI, there is always residual risk of recurrence. Thus, he suggested that residual risk can be divided into

  • residual lipid-driven risk and
  • residual inflammatory-driven risk.

canakinumab might prove to be most useful if it were given to an identified high-responder group. Findings in the hs-CRP responders:

Patients whose hs-CRP declined to 1.8 mg/L or less had a much more robust response. In that subgroup, the number needed to treat to prevent a primary endpoint event was 50 at 2 years and 30 at 3.7 years.

He noted that after a single injection responders have a significant reduction in highly sensitive-CRP and it is those patients who would benefit from continuing on treatment.

“Maybe that first dose could be free,” Ridker added.

Co-investigator, Peter Libby, MD, of Massachusetts General Hospital, put it this way: 30 days after an MI, when a patient is on statin therapy and stable,

  • physicians could check LDL and then initiate more aggressive statin therapy if it is not well-controlled. Similarly,
  • physicians should check hs-CRP, and if it is elevated — 2.0 mg/L or higher — initiating anti-inflammatory therapy targeting interleukin-1 beta would be an option

Interestingly, the treatment had no effect on lipids, which suggests that the benefit was all attributable to the anti-inflammatory activity. 

In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), 150 mg of canakinumab every 3 months reduced high-sensitivity C-reactive protein (hs-CRP) levels by an average of 37% compared with placebo and achieved a 15% reduction in cardiovascular events — mostly MIs — compared with placebo, Paul Ridker, MD, reported here at the European Society of Cardiology 2017 congress.

The CANTOS findings were simultaneously published online by the New England Journal of Medicine.

After a median follow-up of 3.7 years, the event rate was 4.5 per 100 person-years in the placebo group versus 3.86 events per 100 person-years in the canakinumab 150 mg group. Two other arms — canakinumab 50 mg and 300 mg — also achieved reductions in events (4.11 and 3.90 per 100 person-years, respectively) but only the 150-mg dose achieved a statistically significant reduction.

There was no reduction in mortality. The trial recruited patients who had a history of MI and a hs-CRP level of 2.0 mg/L or higher.

  • There was no significant difference in all-cause mortality (HR for all canakinumab doses versus placebo, 0.94; 95% CI 0.83-1.06; P=0.31).

Benefits of Anti-inflammatory Canakinumab

although there was no cardiovascular mortality benefit, there was 30% reduction in need for bypass surgery, angioplasty, and heart failure — all of which means a significant improvement in quality of life. And treatment was also associated with a reduction in gout, rheumatoid arthritis, and osteoarthritis, he said.

Cancer Benefit

There was an apparent decrease in risk of cancer, a finding that was elucidated in a Lancet paper also published today. In the cancer analysis, also authored by Ridker, total cancer mortality was lower only in the 300-mg group, but “[i]ncident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0.61 [95% CI 0.39–0.97]; P=0.034) and 300 mg groups (HR 0.33 [95% CI 0.18–0.59] P<0.0001.”

Negative findings

  • Canakinumab was associated with a higher incidence of fatal infection than placebo — the rate was 0.18 in the 3,344 patient placebo group versus 0.32 among the 6,717 patients who received any dose of the drug, which worked out to 23 deaths versus 78 deaths (P=0.02).
  • VIEW VIDEO

Study Author Paul M. Ridker. Interviewed by Peggy Peck, Editor-in-Chief of MedPage Today

https://www.medpagetoday.com/meetingcoverage/esc/67529

  • VIEW VIDEO

Clinical Impact or No Clinical Impact

Anthony DeMaria, MD discusses the major trials from ESC and what impact, if any, they will have on clinical practice.
Benefit vs Price
On June 28 heart failure specialist Milton Packer, MD, wrote this in his MedPage Today blog: “My prediction: [canakinumab] may cost $64,000 for a 15-20% reduction in the risk of a major cardiovascular event, without decreasing cardiovascular death by itself.
Amgen’s Repatha (evolocumab) is a PCSK9 inhibitor that aggressively lowers lipids and is approved for patients who fail statin therapy, including patients with heterozygous or homozygous familial hypercholesterolemia. But while the lipid reductions with the PCSK9 therapy are impressive, and the FOURIER trial found a 15% reduction in events with treatment, neither evolocumab nor alirocumab (Praluent), a PCSK9 inhibitor from Sanofi/Regeneron have achieved wide uptake as payers balk at the high price tags for the drugs.
Other anti-inflammatory agents:
Ridker said. For example, “we have a [National Heart, Lung, and Blood Institute] trial of methotrexate (RA agent) that is on-going. If that proves to be effective, it would be only pennies per treatment.” At the press conference, Ridker said the methotrexate trial has “randomized about 4,000 patients, and we will need to get to 7,000 so it will be a few years before we have results.”

SOURCE

https://www.medpagetoday.com/meetingcoverage/esc/67529

176 articles on monoclonal antibody

https://pharmaceuticalintelligence.com/?s=monoclonal+antibody

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 Cholesterol Lowering Novel PCSK9 drugs: Praluent [Sanofi and Regeneron] vs Repatha [Amgen] – which drug cuts CV risks enough to make it cost-effective?

Reporter: Aviva Lev-Ari, PhD, RN

 

UPDATED on 1/15/2019

In the patent fight over PCSK9 inhibitors, the Supreme Court refused to hear Amgen’s appeal of a 2017 court decision allowing Sanofi and Regeneron to continue selling alirocumab (Praluent). Amgen still has a new patent trial starting in Delaware federal court next month, FiercePharma reports.

Amgen’s Repatha hits wall at SCOTUS but presses ahead—new price breaks included

Amgen has been trying since 2015 to protect its PCSK9 cholesterol drug Repatha by keeping Sanofi and Regeneron’s rival Praluent off the market, even going as far as to ask the U.S. Supreme Court to review an ongoing patent fight.

But that attempt fell short this week as SCOTUS refused to hear the company’s appeal of a 2017 court decision allowing Sanofi and Regeneron to continue selling its head-to-head rival.

Amgen isn’t giving up the fight, though. The company is prepping for a new patent trial starting in Delaware federal court next month. And it’s responding to long-standing criticism of the high cost of PCSK9 drugs, which hit the market in 2015 at list prices of about $14,000 a year.

Amgen had already brought the price of the biweekly version of Repatha down to $5,850 per year before discounts and rebates, and late Monday it said it would lower cost of the monthly injectable dose to that same level.

SOURCE

UPDATED on 11/13/2018

ODYSSEY OUTCOMES: Alirocumab Cost-effective at $6000 a Year

Marlene Busko

November 11, 2018

CHICAGO — Treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab (Praluent, Sanofi/Regeneron) is cost-effective at $6319 a year when the willingness-to-pay threshold is the generally accepted $100,000 per quality-adjusted life-year (QALY), new research reports.

Deepak L. Bhatt, MD, MPH, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts, presented these cost-effectiveness findings for alirocumab, based on data from the ODYSSEY OUTCOMES trial, here at the American Heart Association (AHA) 2018 Scientific Sessions

As previously reported, results from ODYSSEY OUTCOMES were presented at American College of Cardiology (ACC) 2018 Annual Scientific Session in March and the study was published November 7 in the New England Journal of Medicine.

Strengths of the current cost analysis include that it used actual trial data as opposed to modeling estimates, Bhatt pointed out to theheart.org | Medscape Cardiology.

SOURCE

https://www.medscape.com/viewarticle/904744?nlid=126063_3866&src=WNL_mdplsfeat_181113_mscpedit_card&uac=93761AJ&spon=2&impID=1799507&faf=1

 

Did Amgen’s Repatha cut CV risks enough to make it cost-effective? Analysts say no

Sanofi, Regeneron’s Praluent pulls off PCSK9 coup with 29% cut to death risks in most vulnerable patients
SEE our curations on PCSK9 drugs:

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ODYSSEY Outcomes trial evaluating the effects of a PCSK9 inhibitor, alirocumab, on major cardiovascular events in patients with an acute coronary syndrome to be presented at the American College of Cardiology meeting on March 10.

Reporter: Aviva Lev-Ari, PhD, RN

 

For PCSK9 inhibitors, the effect on major adverse cardiovascular events has always fallen short of expectations based on cholesterol lowering.

But cardiovascular risk reduction is complicated. There is more to the puzzle than cholesterol. Some drugs lower both cholesterol and prevent cardiovascular events, but some people think that the two effects are actually not that closely related.

Milton Packer MD

https://www.medpagetoday.com/blogs/revolutionandrevelation/71435

In a previous trial (FOURIER), another PCSK9 inhibitor had only a modest benefit on its primary endpoint, and it did not reduce cardiovascular death, although the magnitude of cholesterol lowering was striking.

In another trial (SPIRE), a third PCSK9 inhibitor, the clinical trial was terminated prematurely by Pfizer because of reduction of the effect of the drug (a humanized but not fully humanized antibody) due to development of neutralizing antibodies in some of the patients. Actually, in patients treated for more than a year who did not develop neutralizing antibodies, a beneficial effect was seen.

The ODYSSEY Outcomes trial is evaluating the effects of a PCSK9 inhibitor,alirocumab, on major cardiovascular events in patients with an acute coronary syndrome within the prior year. The drug lowers serum cholesterol dramatically, and some are hopeful that that effect will translate into an important reduction in the risk of major adverse cardiovascular events. If you believe that cholesterol reduction inevitably leads to the prevention of cardiovascular death, myocardial infarction and stroke, then you would have high expectations for the ODYSSEY trial.

ODYSSEY. The trial uses a somewhat more aggressive treatment strategy and has a longer follow-up period than its predecessors. So maybe the benefit will be large. Maybe the drug will even reduce cardiovascular death or all-cause mortality.

In order to enrich the population for cardiovascular events, the trial enrolled patients with an acute coronary syndrome within the prior year. These patients are at high risk of having a recurrence. The problem is that risk is not necessarily related to changes in cholesterol, especially the events occurring early in the trial. And in this type of trial, the analysis tends to give extra weight to early events.

Trials like ODYSSEY are often designed to stop early if the results are unbelievably impressive. The ODYSSEY trial wasn’t stopped early.

the patients entering the ODYSSEY trial are starting out with a serum LDL <100 mg/dL or even <90 mg/dL. Is cholesterol really playing an important role at that level, especially when compared with noncholesterol factors?

SOURCE

https://www.medpagetoday.com/blogs/revolutionandrevelation/71435

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