PCSK9 Inhibitor Praluent Added to Statins Improved Lipid Profile in Diabetes

MedicalResearch.com Interview with:

Dr-Robert-R-Henry.jpg

Dr. Henry

Robert R. Henry, M.D.
Professor of Medicine
Member of the ODYSSEY DM Steering Committee and
Director of the Center for Metabolic Research
VA San Diego Healthcare System

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

Response: The ODYSSEY DM-DYSLIPIDEMIA trial was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 patients with type 2 diabetes with mixed dyslipidemia at high cardiovascular (CV) risk, not adequately controlled with maximally tolerated dose (MTD) statins. The primary endpoint was percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24.

In ODYSSEY DM-DYSLIPIDEMIA, Praluent 75 mg was added to MTD statins, with dose adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose.

Results from the ODYSSEY DM-DYSLIPIDEMIA study found that Praluent added to MTD statins showed significant reduction in non-HDL-C and other lipid parameters compared to those on usual care.

Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was -32.5 percent (p<0.0001).

Praluent in combination with MTD statins reduced LDL-C by 43 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001). Treatment with Praluent also improved the overall lipid profile.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Furthermore, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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Adding Praluent (Alirocumab) To Statins Reduces LDL in High Cardiovascular Risk Diabetics

MedicalResearch.com Interview with:

Lawrence Leiter, M.D. MDCM, FRCPC, FACP, FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada

Dr. Lawrence Leiter

Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA
Chair of the ODYSSEY DM Steering Committee and
Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute
St. Michael’s Hospital
University of Toronto, Canada

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

Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24.

Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose.

Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified.

There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk.

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Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World.

MedicalResearch.com Interview with:
Amane Harada, PhD
Senior Researcher
Central Research Laboratories, Sysmex Corporation
Kobe, Japan

Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD
Associate Professor
Division of Evidence-based Laboratory Medicine
Kobe University Graduate School of Medicine
Kobe, Japan 


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

Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions.

Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease.

However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical.

To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”.

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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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