Praluent Plus Statins Reduce LDL In High Risk Cardiovascular Patients

MedicalResearch.com Interview with:

VP Head of Cardiovascular Development and Head Global Cardiovascular Medical Affairs Sanofi

Dr. Edelberg

Dr. Jay Edelberg MD, PhD
VP Head of Cardiovascular Development and
Head Global Cardiovascular Medical Affairs
Sanofi 

MedicalResearch.com: What should readers take away from the data that Sanofi and Regeneron is presenting at ESC Congress 2017?   

Response: This year at European Society of Cardiology (ESC,) we are pleased to present analyses that further demonstrate additional efficacy and tolerability of Praluent (alirocumab).

While statins remain the first-line treatment, Praluent has shown a consistent benefit as an additional therapy to high-intensity statins in patients with clinical atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH), allowing many patients to achieve low-density lipoprotein (LDL) cholesterol levels previously considered unattainable in this patient population.

Our data further emphasize the need for additional cholesterol-lowering options in these high cardiovascular (CV) risk patient populations, including individuals living with diabetes 

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Positive Emotions Predict Health Lipid Profiles In Western, But Not Eastern Cultures

MedicalResearch.com Interview with:

Jiah Yoo Ph.D. Student in Social Psychology University of Wisconsin-Madison Madison, WI 53706 

Jiah Yoo

Jiah Yoo
Ph.D. Student in Social Psychology
University of Wisconsin-Madison
Madison, WI 53706 

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

Response: A growing number of studies have shown that positive emotions predict better physical health. However, a caveat of these findings is that most studies have been conducted with Western samples. As cultural psychologists, we have learned that European American cultural contexts are particular in that positive emotions are highly valued and emphasized. For example, in East Asian cultures, it is a commonly shared view that positive emotions have some dark sides such as that they are fleeting, may attract unnecessary attention from others, and can be a distraction from focusing on important tasks. Given the cultural differences in emotions, we thought it would be important to test whether the established link between positive emotion and enhanced physical health are relevant to other cultural contexts, such as those in East Asia.

We focused on blood lipids profiles, one of the major risk factors for heart diseases, as objective measures of health. Because of the global prevalence of coronary artery diseases, blood lipids are considered important indices of biological health in many Western and East Asian countries. In addition, blood lipids are largely influenced by lifestyles and behavioral factors so we further tested the role of various health behaviors (i.e., dietary habits, body mass index, smoking, alcohol consumption) in the lipids-emotion link in different cultures.

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Hyperlipidemia Linked To Lower Breast Cancer Mortality, Perhaps Due To Statin Therapy

MedicalResearch.com Interview with:

Dr Rahul Potluri Senior author and founder of the ACALM Study Unit Aston Medical School Aston University Birmingham, UK

Dr. Potluri

Dr Rahul Potluri
Senior author and founder of the ACALM Study Unit
Aston Medical School
Aston University
Birmingham, UK

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

Response: The links between hyperlipidaemia and cancer has been exciting scientists in recent years.  We have previously shown an association with breast cancer and hyperlipidaemia using a cross-sectional dataset in 2014.

In 2016 we showed that in patients with the four main cancers in the UK (namely Breast, Lung, Colon and Prostate) that the presence of hyperlipidaemia improved the long term mortality and prognosis of these patients.  In this study utilising a big data, longitudinal study methodology, we looked at 16043 healthy women above the age of 40 with hyperlipidaemia and compared these to an age and gender matched control sample of 16043 healthy women without high cholesterol. We then followed up these patients and found that subsequent breast cancer rates in the women with hyperlipidaemia were 45% lower. Subsequent mortality in those patients who developed breast cancer was also 40% lower in the hyperlipidaemia group compared to the non-hyperlipidaemia controlled sample.

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PCSK 9 Inhibitors May Be Cost Effective For Subset of High Risk Patients, If Price is Right

MedicalResearch.com Interview with:

Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of Cardiovascular Medicine and Science Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief of Clinical Cardiology, UCLA Division of Cardiology Co-Director, UCLA Preventative Cardiology Program David Geffen School of Medicine at UCLA Los Angeles, CA, 90095-1679

Dr. Gregg Fonarow

Gregg C. Fonarow, MD, FACC, FAHA
Eliot Corday Professor of Cardiovascular Medicine and Science
Director, Ahmanson-UCLA Cardiomyopathy Center
Co-Chief of Clinical Cardiology, UCLA Division of Cardiology
Co-Director, UCLA Preventative Cardiology Program
David Geffen School of Medicine at UCLA
Los Angeles, CA 

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

Response: The study identifies the clinical and economic consequences of treating a population of patients with established atherosclerotic cardiovascular disease (ASCVD ) at high-risk of cardiovascular (CV) events and defines the cost-effectiveness of the PCSK-9 inhibitor evolocumab under various clinical scenarios. The analysis is based on the clinical outcomes from the Repatha Outcomes Study (FOURIER) in patients with established atherosclerotic cardiovascular disease (ASCVD), such as those who have already had a heart attack or stroke who require additional therapy.

This is the first cost-effectiveness assessment of evolocumab using a model based on a high-quality outcomes trial, combined with U.S. clinical practice data. The analysis identifies the types of high-risk patients for whom this therapy is both clinically beneficial and cost-effective. This study utilized cost-effectiveness and value thresholds employed by the World Health Organization and the American College of Cardiology/American Heart Association.

Evolocumab was found to exceed generally accepted cost-effectiveness thresholds at current list price. However, this medication could be a cost-effective treatment for patients with established ASCVD in the U.S. when the net price is at or below $9,669 per year.

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Familial Hypercholesterolemia: “Junk” RNA May Facilitate Gene Therapy

MedicalResearch.com Interview with:

Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 

Dr. Sallam

Tamer Sallam, MD PhD
Assistant Professor of Medicine
Co-Director UCLA Center for Lipid Management
Lauren B. Leichtman and Arthur E. Levine CDF Investigator
Assistant Director, STAR Program
Division of Cardiology, Department of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, California 90095-1679

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

Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease.

In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases.

Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments.

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Even After Rebates, Use of PCSK9 Inhibitor Would Still Cost Over $5 Million To Prevent One Stroke

MedicalResearch.com Interview with:

Inmaculada Hernandez, PharmD, PhD Assistant Professor of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh, PA 1526

Dr. Hernandez

Inmaculada Hernandez, PharmD, PhD
Assistant Professor of Pharmacy and Therapeutics
University of Pittsburgh School of Pharmacy
Pittsburgh, PA 1526

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

Response: A few months ago, the results of the FOURIER trial were published. This trial was the first one to evaluate the efficacy of PCSK9 inhibitors in the prevention of cardiovascular events, since the approval of these agents was based on trials that evaluated their efficacy in reducing levels of LDL-C. The results of the FOURIER trial did not meet the expectations generated by prior studies that had simulated how much the risk of cardiovascular events should decrease based on the observed reduction in LDL-C levels. A few hours after the publication of the results of the FOURIER trial, Amgen (evolocumab´s manufacturer) announced that it would be willing to engage in contracts where the cost of evolocumab would be refunded for those patients who suffer a heart attack or a stroke while using the drug.

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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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