Improving Statin Adherence Would Reduce Need For Expensive PCSK9 Inhibitors

MedicalResearch.com Interview with:
Julia M. Akeroyd, MPH

Center for Innovations in Quality, Effectiveness, and Safety (IQuESt)
Michael E. DeBakey Veteran Affairs Medical Center
Salim S Virani, MBBS, Ph.D.
Baylor College of Medicine

MedicalResearch.com: What is the background for this study?

Response: In the recently published Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, treatment with evolocumab resulted in a 15% relative (1.5% absolute) risk reduction of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) at a median follow-up of 2.2 years. Given the high cost of evolocumab, there is a need to identify what proportion of ASCVD patients would qualify for evolocumab based on FOURIER entry criteria and how eligibility would change if maximal doses of evidence-based lipid lowering therapies were required.

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Fewer Heart Attacks and Strokes After Trans-Fat Restriction Laws in New York

MedicalResearch.com Interview with:

Eric J. Brandt, MD Yale University Cardiovascular Disease Fellow

Dr. Eric Brandt

Eric J. Brandt, MD
Yale University
Cardiovascular Disease Fellow

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: From previous studies we know that industrial trans fatty acid (trans fat) consumption is linked to elevated risk for cardiovascular disease. Even small amounts of consumption can be deleterious to cardiovascular health. In New York state, there were 11 counties that restricted the use of trans fatty acids in eateries. We compared hospitalization for heart attacks and stroke from 2002 through 2013 in counties that did and did not have restrictions.

Our study found that when comparing populations within New York state that restricted the use of trans fat, compared to those that did not, there was an associated additional decline beyond temporal trends for heart attacks and stroke events combined by 6.2%.

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Older Women Face Greater Risk of Diabetes From Statins

MedicalResearch.com Interview with:
Dr Mark Jones, Senior Lecturer
Faculty of Medicine and Biomedical Sciences, School of Public Health
The University of Queensland

MedicalResearch.com: What is the background for this study?

Response: Multiple clinical trials have shown statins reduce LDL cholesterol, cardiovascular events, and all-cause mortality. However statins are also associated with adverse events, including type 2 diabetes. There have been very few older women included in statin trials hence effects of the drug in this population are somewhat uncertain. Also, more generally, results from clinical trials may not translate well into clinical practice.

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Many Eligible Groups Not Receiving Recommended Statin Therapy

MedicalResearch.com Interview with:
Dr. Yashashwi Pokharel MD, MSCR
Department of Cardiovascular Research
Saint Luke’s Mid-America Heart Institute
Kansas City, Missouri and
Salim S. Virani, MD PhD, FACC, FAHA
Associate Professor, Section of Cardiovascular Research
Associate Director for Research, Cardiology Fellowship Training Program
Baylor College of Medicine
Investigator, Health Policy, Quality and Informatics Program
Michael E. DeBakey Veterans Affairs Medical Center HSR&D Center of Innovation
Staff Cardiologist, Michael E. DeBakey Veterans Affairs Medical Center
Houston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Unlike the previous cholesterol management guideline that recommended use of either statin and non-statin therapy to achieve low density lipoprotein cholesterol (LDL-C) target, the 2013 American College of Cardiology/American Heart Association cholesterol management guideline made a major paradigm shift by recommending statin focused treatment in 4 specific patient groups and replaced LDL-C target with fixed statin intensity treatment (moderate to high intensity statin therapy).

With this change, it was speculated that a large number of patients would be eligible for statin treatment (in one study, up to 11.1% additional patients were expected to be eligible for statin therapy). Our study provided the real world trends in the use of statin and non-statin lipid lowering therapy (LLT) from a national sample of cardiology practices in 1.1 million patients 14 months before and 14 months after the release of the 2013 guideline.

We found a modest, but significant increasing trend in the use of statin therapy in only 1 of the 4 patient groups eligible for statin therapy (i.e., 4.3% increase in the use of moderate to high intensity statin therapy in patients with established atherosclerotic cardiovascular disease). We did not find any significant change in non-statin LLT use. Importantly, about a third to half of patients in statin eligible groups were not receiving moderate to high intensity statin therapy even after the publication of the 2013 guideline.

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PCSK9 Inhibition with Alirocumab Increases Removal of LDL Cholesterol

MedicalResearch.com Interview with:
Henry N. Ginsberg, MD

Irving Institute for Clinical and Translational Research
Columbia University
Columbia College of Physicians and Surgeons
New York, NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies in mice and cells have identified increased hepatic low density lipoprotein (LDL) receptors as the basis for LDL lowering by PCSK9 inhibitors, but there have been no human studies characterizing the effects of PCSK9 inhibitors on lipoprotein metabolism, particularly effects on very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) or LDL metabolism.

This study in 18 healthy subjects, found that alirocumab decreased the number of IDL and LDL particles in the circulation, and their associated cholesterol and apoB levels by increasing efficiency of the clearance of IDL and LDL. There were not effects on VLDL metabolism. The increased clearance of IDL meant that less LDL was produced from IDL, which is the precursor of LDL. Thus, the dramatic reductions in LDL cholesterol resulted from both less LDL being produced and more efficient clearance of LDL. These results are consistent with increases in LDL receptors available to clear IDL and LDL from blood during PCSK9 inhibition.

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Treatment With Liraglutide (Victoza) Reduces Fat Around the Heart

MedicalResearch.com Interview with:

Gianluca Iacobellis MD PhD Professor of Clinical Medicine Division of Endocrinology, Diabetes and Metabolism Department of Medicine University of Miami, FL

Dr. Gianluca Iacobellis

Gianluca Iacobellis MD PhD
Professor of Clinical Medicine
Division of Endocrinology, Diabetes and Metabolism
Department of Medicine
University of Miami, FL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We know that epicardial fat, the visceral fat of the heart, is associated with coronary artery disease, diabetes and obesity. My studies have shown that epicardial fat can be easily measured with non invasive imaging procedures. Remarkably, epicardial fat has recently emerged as therapeutic target responding to medications targeting the fat. Liraglutide, a GLP-1 analog has shown to provide modest weight loss and beneficial cardiovascular effects beyond its glucose lowering action. So , we sought to evaluate the effects of liraglutide on epicardial fat.

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Statins Linked to Reduced Risk of Venous Thromboembolism

MedicalResearch.com Interview with:

Setor Kunutsor BSc MD MPhil(cantab) PhD(cantab) Research Fellow/Epidemiologist Musculoskeletal Research Unit University of Bristol School of Clinical Sciences Learning & Research Building (Level 1) Southmead Hospital

Dr. Setor Kunutsor

Setor Kunutsor BSc MD MPhil(cantab) PhD(cantab)
Research Fellow/Epidemiologist
Musculoskeletal Research Unit
University of Bristol
School of Clinical Sciences
Southmead Hospital

MedicalResearch.com: What is the background for this study?

Response: Statins are well established for the prevention of cardiovascular disease and this is based on their ability to lower levels of circulating lipids in the blood. However, statins are also known to have pleotropic effects and these include potential protective effects on multiple disease conditions.

Based on their anti-inflammatory and antithrombotic properties, there have been suggestions that statins may prevent venous thromboembolism (VTE) (which comprises of pulmonary embolism and deep vein thrombosis). The evidence is however uncertain. Several studies utilizing both observational cohort and randomized controlled designs have been conducted to evaluate whether statin therapy or use is associated with a reduction in the incidence of VTE, but the results have been inconclusive. In a recent review that was published in 2012, Rahimi and colleagues pooled the results of several randomized controlled trials (RCTs), but found no significant reduction in the risk of VTE with statin therapy [REF]. Given the publication of new studies since this study was published and the existing uncertain evidence on the effect of statins on VTE, we decided it was time to bring all the evidence together and evaluate if statin therapy really did have a protective effect on the risk of venous thromboembolism.

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Meta-analysis of Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk

MedicalResearch.com Interview with:
Dominik D Alexander, PhD, MSPH

Principal Epidemiologist
EpidStat Institute
Ann Arbor, MI Seattle, WA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years, the body of scientific literature on n-3 LCPUFA (EPA/DHA) intake and coronary heart disease (CHD) risk has exploded with mixed results. It was only logical to conduct a comprehensive meta-analysis of randomized controlled trials (RCTs) to estimate the effect of EPA+DHA on CHD, and to conduct a comprehensive meta-analysis of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk.

Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA
provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event.

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Some Type 2 Diabetics May Benefit From Adding Fenofibrate To Statins

MedicalResearch.com Interview with:

Marshall B. Elam PhD MD Professor Pharmacology and Medicine (Cardiovascular Diseases) University of Tennessee Health Sciences Center Memphis

Dr. Marshall B. Elam

Marshall B. Elam PhD MD
Professor Pharmacology and Medicine
(Cardiovascular Diseases)
University of Tennessee Health Sciences Center
Memphis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This manuscript presents the findings of extended follow up of patients with Type 2 Diabetes who were treated with fenofibrate, a member of a group of triglyceride lowering medications known as fibrates or PPAR alpha agonists, as part of the Action to Control Cardiovascular Risk in T2DM (ACCORD) study.

ACCORD was designed to test the effect of intensive treatment of cardiovascular risk factors including blood glucose, blood pressure and lipids on risk of heart attack, stroke and cardiac death in patients with Type 2 Diabetes.

The lipid arm of ACCORD tested the hypothesis that adding fenofibrate to statin therapy would further reduce risk of these cardiovascular events.

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Familial Hypercholesterolemia Diagnosed Through EHR and Genetics Data

MedicalResearch.com Interview with:

Michael F. Murray MD Geisinger Health System Danville, PA 17822

Dr. Michael Murray

Michael F. Murray MD
Geisinger Health System
Danville, PA 17822

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The DiscovEHR cohort was formed as a result of a research collaboration between Geisinger Health System and Regeneron Pharmaceuticals. There are over 50,000 patient participants in the cohort who have volunteered to have their de-identified genomic sequence data linked to their de-identified EHR data for research purposes. We report in this paper findings around the identification of 229 individuals (1:256) with pathogenic or likely pathogenic variants in one of the three genes (LDLR, APOB, PCSK9) associated with Familial Hypercholesterolemia (FH). The study found that these individuals are unlikely to carry a diagnosis of FH and are at risk for early coronary artery disease.

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PCSK9 Inhibitor Praluent Substantially Reduced LDL-C Cholesterol

MedicalResearch.com Interview with:

Dr. Eli M. Roth MD, FACC President, Medical Director Sterling Research Group Cincinnati, OH

Dr. Eli Roth

Dr. Eli M. Roth MD, FACC
President, Medical Director
Sterling Research Group
Cincinnati, OH

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: At this year’s AHA 2016, we presented a pharmacodynamics analysis of ODYSSEY CHOICE I, which evaluated the effects of Praluent 300 mg administered every four weeks (Q4W) for 24 weeks in hypercholesterolemia patients at moderate to very high cardiovascular risk who were on maximally tolerated statin or no statin and/or other lipid-lowering therapies.

The pharmacodynamic analysis of CHOICE I in patients on statins supports the use of Praluent 300 mg Q4W as an alternative starting dose for patients who prefer a Q4W dosing regimen and demonstrates the value of LDL-C based dosing interval adjustment. The findings from this analysis were consistent with prior ODYSSEY Phase 3 studies, showing that Praluent substantially reduced circulating free PCSK9 concentration, resulting in significant LDL-C reductions. Additionally, Praluent was generally well tolerated.

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Byproduct of Sweet Potato Waste Offers Clue To Lipid Metabolism

MedicalResearch.com Interview with:
Dr. Koji Ishiguro

National Agriculture and Food Research Organization
Japan

MedicalResearch.com: What is the background for this study?

Response: -Sweet potato (Ipomoea batatas L.) roots are not only used for human consumption, they are used to make starch materials, processed foods, and distilled spirits in Japan. Starch use accounts for about 15% (131,500 tons) of total sweet potato production. Starch residues are discharged during starch production and are mainly used in animal feed and compost. Large amounts of the wastewater, which can cause serious environmental problems, are discarded after clarification. Investigation into the uses of the by-products of the sweet potato starch industry would benefit both the environment and industry.

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