Novel siRNA targeting therapy lepodisiran results in a dose-dependent and sustained reduction in Lipoprotein(a)

Key Points:

  • There are currently no approved targeted therapies for the reduction of Lp(a).
  • In this Phase I study, a novel siRNA therapy (lepodisiran) was tested in escalating doses and compared to placebo in 48 patients. Lp(a) concentrations and safety events were examined for 48 weeks.
  • Single-dose lepodisiran administration resulted in up to 94% reduction in Lp(a) at 48 weeks and was generally well-tolerated, supporting further development of this therapy.

Continue reading

EPIC-STEMI: Early Routine PCSK-9 Use Added to High Intensity Statin Reduces LDL after Primary PCI for STEMI

Key Points:

  • Early high-intensity statin therapy is standard of practice in acute STEMI patients, but this is often insufficient to achieve LDL targets. PCSK-9 therapy has never been tested as routine therapy in STEMI.
  • In the EPIC STEMI trial, routine PCSK-9 initiation in addition to high-intensity statin prior to primary PCI resulted in a 22% LDL reduction at 6 weeks relative to sham, with a higher proportion of patients achieving therapeutic LDL targets.

Continue reading

Relationship Between Omega-3 Fatty Acid Levels And Major Adverse Cardiovascular Outcomes In Patients With High Cardiovascular Risk


  • There is not enough evidence to state whether Omega-3 Fatty Acid levels are beneficial or harmful against major adverse cardiovascular events in patients with high cardiovascular risk.

Dr. Steven E. Nissen is the chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic and Professor of Medicine at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University.  Prior to summarizing Dr. Nissen’s late breaking trial at presented May 16, Day 2 of ACC 2021 that is concurrently published in JAMA Cardiology . Continue reading

TIPS-3 Trial: The Combination of Polypill and Aspirin Administered to Patients at Intermediate Risk Led to a Lower Incidence of Cardiovascular Events Compared With Double Placebo

A recent trial by Dr. Salim Yusuf, published in The New England Journal of Medicine, indicated that combination therapy with aspirin plus a polypill (consisting of a statin plus three blood-pressure-lowering drugs) can reduce the incidence of cardiovascular events compared with placebo among participants without established cardiovascular disease, but at moderate cardiovascular risk.

Continue reading

PREMIER Trial Shows Incremental Plaque Regression by a Single Lipid Apheresis and Maintained Statin Therapy in ACS Patients Treated With PCI

A recent study by Dr. Banerjee, published in Circulation: Cardiovascular Interventions, demonstrated the efficacy and safety of low-density lipoprotein (LDL) lowering therapy via a single LDL apheresis treatment plus ongoing statin therapy in nonfamilial hyperlipidemia acute coronary syndrome patients treated with the percutaneous coronary intervention (PCI).
Continue reading

ORION-1: 1-Year Follow-Up Data Affirms 2-dose Regimen Using 300 mg of Inclisiran For Persistent LDL-C Lowering 360-day follow-up results published in September edition of JAMA Cardiology

A randomized, double blind, placebo-controlled, phase II clinical trial studying the effect of a novel protein proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis inhibitor (inclisiran) on serum low density lipoprotein cholesterol (LDL-C) levels has shown that twice a year subcutaneous injections of inclisiran leads to a sustained dose-dependent reduction in serum LDL-C levels over a period of 1 year.

Continue reading

EWTOPIA 75 Trial: Lowering LDL-Cholesterol with Ezetimibe Prevents Cardiovascular Events in the Elderly

Individuals older than 75 years treated with ezetimibe had a significantly lower risk of atherosclerotic cardiovascular events over 4 years compared with standard care, according to the results of the EWTOPIA 75 trial recently published in Circulation.

Continue reading

Positive Correlation Found Between Combined Life-time Exposure of Decreased LDL-C and Low Systolic BP in Lowering the Risk of Cardiovascular Disease Mendelian randomization analyses involving approximately half a million participants reveals the association of lifelong genetic exposure to lower levels of low-density lipoprotein cholesterol and lower systolic blood pressure with lower cardiovascular risk

A recent study by Brian A. Ference et al. based on a UK Biobank study, published in JAMA, has shown that life-time exposure to decreased low-density lipoprotein cholesterol (LDL-C) levels and low systolic blood pressure (SBP) leads to a decreased lifetime risk of cardiovascular disease. Nonetheless, these findings do not constitute the quantified benefit of treating these risk factors in decreasing the life-time cardiovascular disease risk.

This randomized study included the data from 438, 952 individuals who were the participants of the UK Biobank study with the mean age of 65.2 years (range: 40.4 – 80.0 years) and 54.1% female participants. Participants were divided into a total of 4 groups, and 4 x 4 factorial reasoning was carried out. First participants were divided into 2 groups based on having a genetic LDL-C score being equal to or lower than, or higher than the median value. Second, they were further subdivided into 2 groups based on having their genetic systolic BP score being equal to, or lower than, or higher than the median value. The reference group further included 3 groups with each individual group having a higher LDL-C genetic score than the median, higher SBP scores than the median, and combined LDL-C and SBP genetic scores higher than the median, respectively. Differences in the plasma LDL-C, SBP, and cardiovascular event rates between the groups were compared to evaluate the correlations with the lifetime cardiovascular disease risk. The primary outcome included major coronary events which were characterized as a composite of coronary death, coronary revascularization, or nonfatal myocardial infarction. The key secondary outcomes were major cardiovascular events defined as the occurrence of a major coronary event or ischemic stroke.

When compared with the reference group, participants having LDL-C genetic scores higher than the median had 14.7-mg/dL lower LDL-C levels with an Odds ratio of 0.73 for major coronary events (95%CI: 0.70 – 0.75; P < 0.001). Participants with SBP genetic scores higher than the median had 2.9 mmHg lower SBP with an Odds ratio of 0.82 for major coronary events (95%CI: 0.79 – 0.85; P < 0.001). Finally, the participants in the group with both genetic scores higher than the median had 13.9 mg/dL lower LDL-C, 3.1 mmHg lower SBP, with an Odds ratio of 0.61 for major coronary events (95%CI: 0.59 – 0.64; P < 0.001). In a 4×4 factorial analysis, exposure to increasing genetic risk scores and lower LDL-C levels and SBP was associated with dose-dependent lower risks of major coronary events. In a meta-regression analysis, combined exposure to 38.67 mg/dL lower LDL-C and 10 mmHg lower SBP was associated with an Odds ratio of 0.22 for major coronary events (95%CI: 0.17 – 0.26; P < 0.001), and 0.32 for cardiovascular death (95%CI: 0.25 – 0.40; P < 0.001). These findings concluded the positive correlation of lifelong genetic exposure to lower LDL-C levels and lower SBP with the overall lower cardiovascular disease risk without any regard to the magnitude of benefit achieved after treating these risk factors.

There are several limitations to this study, including the lack of evaluation of risks and benefits of medications associated with lowering the LDL-C and SBP. Second, there is a lack of evidence proving that outcomes associated with naturally occurring lower LDL-C or SBP levels are the same as the outcomes associated with extrinsic drug treatment or other interventions to achieve similar plasma LDL-C or SBP levels. Hence, these study findings fail to quantify the amount of benefit gained from various treatments to lower LDL-C, SBP, or both.

HOPE 4: A Comprehensive Community-based Program Surpassing the Barriers in Improving BP Control and Associated Cardiovascular Disease Risk in 2 Middle Income Countries A successful 12-months follow-up open-labeled, cluster-randomized controlled trial

Significant improvement in blood pressure control and related cardiovascular disease (CVD) risk is seen as a result of a potentially effective and pragmatic comprehensive model of care conducted as HOPE 4 trial (Heart Outcomes and Prevention Evaluation-4) presented by Dr. JD Schwalm at the European Society of Cardiology (ESC) Congress 2019 and simultaneously published in The LANCET.

Continue reading

IMPROVE-IT Trial: Intensive Lipid-Lowering Cuts CVD Risk in the Elderly

Among patients hospitalized for an acute coronary syndrome (ACS), adding ezetimibe to simvastatin further reduced the risk of cardiovascular events, and the benefit was ten times greater in the elderly than younger individuals. A secondary analysis of the IMPROVE-IT trial, published in JAMA Cardiology, revealed.

Continue reading

Cohort Study Shows That a New HDL Apolipoproteomic Score Correlates with Both Risk of Coronary Artery Disease and Risk of Cardiovascular Death

In a study led by Dr. Pradeep Natarajan showed that an HDL apolipoproteomic score is associated with coronary artery disease (CAD). Additionally, the study published in the Journal of the American College of Cardiology showed that among individuals with CAD, this score is independently associated with cardiovascular death.

Continue reading

Nationwide Study Shows Pharmacy Closure Associated with Significant Decrease in Adherence to Cardiovascular Medications

According to a new national study led by Dr. Dima M. Qato that was recently published in JAMA Network Open, among 3.1 million Americans 50 years and older filling cardiovascular medications at pharmacies that eventually closed, there was a significant and immediate decline in medication adherence.  This change in adherence persisted over 12 months and was prominent among older adults living in neighborhoods with fewer pharmacies.

Continue reading

Study in China Indicates Current Practice of Lipid-Lowering Treatment Needs Improvement

In an article published in the American Heart Journal, Dr. Yueyan Xing emphasized the need to improve on current lipid-lowering treatment practices in patients with a history of myocardial infarction or revascularization.  Patients with a previous history of acute coronary syndrome are at a high risk of a recurrent coronary event and death. Lowering low-density lipoprotein cholesterol (LDL-C) in these patients is essential in order to reduce the risk of a recurrent event. The authors used the Improving Care for Cardiovascular Disease in China (CCC) Project to assess current lipid-lowering treatment practices in China.

Continue reading

Total Event Analysis from REDUCE-IT Showcases a Substantial Reduction in the Burden of Ischemic Events, Experts Debate Possible Mechanisms of Action of Icosapent Ethyl Presented at ACC 2019, New Orleans, Los Angeles

The total event analysis from the REDUCE-IT trial, presented at ACC 2019 showed that among statin-treated patients with elevated triglycerides and cardiovascular disease or diabetes, icosapent ethyl substantially reduced the burden of first, subsequent, and total ischemic events. The results are exciting as this is one of the first non-LDL targeted trials to demonstrate a cardiovascular benefit, and is likely to be featured in future guidelines. Continue reading

Statin vs Healthy Adherer Effect On Mortality in ASCVD Association of Statin Adherence With Mortality in Patients With Atherosclerotic Cardiovascular Disease

In a vigorous retrospective cohort study published in JAMA, Fatima Rodriguez et al. found an inverse graded association between long-term statin adherence and all-cause mortality using a nationwide sample of the Veterans Affairs Health System, in patients with atherosclerotic cardiovascular disease(ASCVD). The study proposed that there was room for improvement in statin adherence and also stressed on its importance as a measure of secondary prevention of ASCVD. Continue reading

Statins Shown to Reduce Major Adverse Cardiovascular Events in Patients Older Than Seventy Five Years Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials

HMG-CoA reductase inhibitors or as they are commonly known as statins have been postulated to produce significant reductions in major vascular events irrespective of age, but their efficacy and benefit among patients older than 75 years have not been well documented. In a recent meta-analysis published in The Lancet, by The Cholesterol Treatment Trialists’ Collaboration (CTT collaboration), the influence of advancing age and statin therapy on major vascular episodes in 28 statin trials was analyzed. The collaboration found that statins do reduce the risk of vascular events in older people but have no effect, irrespective of age, on non-vascular mortality and cancer incidence. In the past, 14 meta-analyses have been done each with inconsistent evidence about the use of statins among older people (generally >65 years). This gap in evidence concerning the perception of risk-benefit for the use of statins as the primary prevention in people older than 75 years may be one of the reasons explaining why statin therapy is often discontinued in older patients. Unlike these studies, the present meta-analysis conducted by the CTT collaboration analyzed individual participant data from randomized controlled trials of 186, 854 participants who were older than 75 years with a median follow-up of 4·9 years. Continue reading

Coronary Artery Calcium Scoring: A Screening Tool For Statin Prescription In the Primary Prevention of Cardiovascular Disease? Impact of Statins on Cardiovascular Outcomes Following Coronary Artery Calcium Scoring

According to a new study published in the Journal of American College of Cardiology, patients with higher coronary artery calcium (CAC) scores were more likely to achieve benefit from statins in the primary prevention of cardiovascular disease. Continue reading

The Latest Incarnation of the Blood Cholesterol Management Guideline 2018: Numbers Matter, Lower LDL-C is better A Special Report From the American Heart Association and American College of Cardiology

The AHA/ACC 2018 guideline on the management of blood cholesterol, endorsed by at least 10 other medical societies, was published online in the Journal of the American College of Cardiology and in Circulation to coincide with its grand unveiling at the American Heart Association (AHA) Scientific Sessions 2018 in Chicago, Illinois.  Continue reading

CoQ10 supplementation: A Remedy for Statin‐Induced Myopathy? Effects of Coenzyme Q10 on Statin‐Induced Myopathy: An Updated Meta‐Analysis of Randomized Controlled Trials

A meta‐analysis performed by Choi et al., the results of which were published in the Journal of the American Heart Association, indicated that CoQ10 supplementation improved statin‐associated muscle symptoms, suggesting a therapeutic approach for statin‐induced myopathy. Continue reading

Periprocedural loading dose of Atorvastatin reduces MACE in patients with ACS undergoing PCI: Is this a Pleiotropic effect? Timing of Loading Dose of Atorvastatin in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes: Insights From the SECURE-PCI Randomized Clinical Trial

A study by Lopes and his colleagues published in JAMA Cardiology has shown that in patients with ACS undergoing PCI, periprocedural loading doses of atorvastatin appeared to reduce the rate of Major Adverse Cardiovascular Events (MACE) at 30 days, primarily in patients with ST-segment elevation myocardial infarction. Insights from the Statins Evaluation in Coronary Procedures and Revascularization (SECURE-PCI) randomized clinical trial showcased this beneficial effect to be preserved and consistent, regardless of the timing of atorvastatin administration, including within 2 hours before PCI. Continue reading