LPA Gene Variants Linked To Cardiac Events Despite Statins

MedicalResearch.com Interview with:

Wei-Qi Wei, MD, PhD Assistant Professor Department of Biomedical Informatics Vanderbilt University Nashville, TN 37203

Dr. Wei-Qi Wei

Wei-Qi Wei, MD, PhD
Assistant Professor
Department of Biomedical Informatics
Vanderbilt University
Nashville, TN 37203

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

Response: The study was motived by the clinical observation that some patients develop coronary heart disease events despite taking statins, one of our most effective drugs to reduce cardiovascular risk. We collected data within the eMERGE network of people taking statins and monitored them for development of coronary heart disease events over time.  We  conducted a genome-wide association study of those with events compared to those without events.

Our results showed that single nucleotide polymorphisms (SNPs) on the LPA gene were associated with a significantly increased risk of coronary heart disease events. Individuals with the variant were 50% more likely to have an event. More importantly, even among patients who achieved ideal on-treatment LDL cholesterol levels (<70 mg/dL), the association remained statistically significant.

We then did a phenome-wide association study to see if other diseases or conditions were associated with these LPAvariants. The major associated conditions were all cardiovascular. This sort of study can highlight potential other indications for a drug targeting this pathway and suggest potential adverse events that might be experienced from targeting this pathway. Clearly, more and larger studies will be needed to truly understand the potential risks and benefits of a future drug targeting this pathway.  Continue reading

Most Patients With Adverse Reaction To Statins, Can Ultimately Tolerate Them

MedicalResearch.com Interview with:

Alexander Turchin, M.D., M.S. FACMI Associate Professor of Medicine ENDOCRINOLOGY, DIABETES AND HYPERTENSION BRIGHAM AND WOMEN'S HOSPITAL

Dr. Turchin

Alexander Turchin, M.D., M.S. FACMI
Associate Professor of Medicine
ENDOCRINOLOGY, DIABETES AND HYPERTENSION
BRIGHAM AND WOMEN’S HOSPITAL

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

Response: Statins are known to reduce the risk of cardiovascular events and death, and are some of the most commonly prescribed medications. However, many patients stop taking statins, most commonly because of adverse reactions. It has been shown previously that many individuals who discontinued statin therapy after an adverse reaction are ultimately able to tolerate statins, and that reattempting statin therapy after an adverse reaction is associated with reduced risk of cardiovascular events and death. However, optimal patient selection criteria and methods of reattempting treatment with statins are unknown. We therefore conducted this study to identify patient and treatment characteristics associated with an increased chances of successful reattempt of statin therapy after an adverse reaction.

Through analysis of EMR data of over 6,000 patients we found that the following were associated with higher chances of successful statin therapy reattempt:

  • Reattempted treatment with a different statin
  • Patient at high cardiovascular risk (prior history of CAD, stroke or diabetes)

On the other hand, the following were associated with lower chances of success:

  • Adverse reaction was reported in the first year after starting statin therapy
  • Adverse reaction was myalgia or myopathy
  • Previous history of adverse reactions to other (non-statin) medications 

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Statins: Large Disparity Between US/Canadian/UK and European Guidelines

MedicalResearch.com Interview with:

Borge G. Nordestgaard,

Borge G. Nordestgaard

Børge G. Nordestgaard, MD, DMSc
Department of Clinical Biochemistry
Herlev and Gentofte Hospital, Copenhagen University Hospital
Herlev, Denmark

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

Response: Five major organizations recently published guidelines for using statins to prevent atherosclerotic cardiovascular disease  — the American College of Cardiology/American Heart Association (ACC/AHA) in 2013, the United Kingdom’s National Institute for Health and Care Excellence (NICE) in 2014, and in 2016 the Canadian Cardiovascular Society (CCS), the US Preventive Services Task Force (USPSTF), and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS). We applied these five guidelines to a contemporary study cohort of 45,750 40-75 year olds from the Copenhagen General Population Study.

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No Convincing Evidence of Memory Dysfunction Due To Statins

MedicalResearch.com Interview with:

Dr-Beth-Taylor

Dr. Taylor

Beth A. Taylor, PhD
Director of Exercise Physiology Research, Hartford Hospital Associate Professor, Kinesiology
University of Connecticut

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

Response: Hydroxy-methyl-glutaryl (HMG) CoA reductase inhibitors (statins) are the most effective medications for managing elevated concentrations of low-density lipoprotein cholesterol (LDL-C).  Although statins are generally well-tolerated, they are not without side effects, and mild central nervous system (CNS) complaints such as memory loss and attention decrements are the second most commonly reported adverse effect of these drugs.

Studies assessing cognitive effects of statins vary widely and have produced inconclusive findings. Despite the equivocal data on adverse cognitive side effects with statin therapy, in 2012 the FDA announced a safety label change for statins, based on published case reports of memory loss and confusion and data from the Adverse Events Reporting System. One possibility for these equivocal findings is that studies involving the effects of statins on cognition typically have assessed cognitive function using traditional cognitive tests, which may yield small effect sizes and demonstrate high intra-participant variability. This may explain the discrepancy between clinical trials and patient self-reports, and could be addressed by utilizing CNS tests that directly assess brain parameters.

To the best of our knowledge and literature review, this study is the first to investigate the effects of statins on the central nervous system by utilizing fMRI to assess brain neural activation in healthy adults treated with 80 mg atorvastatin or placebo.

We detected few changes attributable to statin therapy with standardized neuropsychological tests, a finding similar to that from previous clinical trials. However, participants on atorvastatin demonstrated altered patterns of neural activation on vs. off statin compared to participants treated with placebo. Unexpectedly, the treatment groups differed at both timepoints. The clinical implications of these findings are unclear and warrant additional clinical trials.

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Current Statin Guidelines May Miss Young Adults At Risk of Heart Attack

MedicalResearch.com Interview with:

Avinainder Singh, M.B.B.S. Research Fellow Cardiovascular Medicine Brigham & Women's Hospital Harvard Medical School Boston, MA

Dr. Singh

Avinainder Singh, M.B.B.S.
Research Fellow
Cardiovascular Medicine
Brigham & Women’s Hospital
Harvard Medical School
Boston, MA 

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

Response: Overall, the incidence of myocardial infarction (MI) in the US has declined. However, it has remained stable in adults <50 years of age.

We evaluated the statin eligibility of a cohort of adults who had an MI at a young age using current guidelines – the 2013 ACC/AHA guidelines for cholesterol treatment and the 2016 USPSTF guidelines on use of statins for primary prevention.

In, our study we found that only 49% of these young adults would have been eligible for statin therapy prior to their MI according the 2013 ACC/AHA guidelines, and only 29% would have been eligible according to the USPSTF guidelines, despite a high prevalence of cardiovascular risk factors. These numbers were even more striking for women where only 18% were eligible for statin therapy according to the USPSTF guidelines.

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Study Finds ACE Inhibitors and Statins Can Be Safe In Type I Diabetes

MedicalResearch.com Interview with:
M. Loredana Marcovecchio, M.D.
Clinical Scientist and
Professor David Dunger M.D.
Director of Research
Professor of Paediatrics
University of Cambridge

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

Response: The efficacy and safety of ACE Inhibitors and statins in adolescents have been shown in the context of hypertension and familial hypercholesterolemia, respectively. However, there is a lack of data on the long-term use of these drugs in those with type 1 diabetes and, in particular, there is no clear indication for their use in patients with increased albumin excretion.

The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) was a multi-centre, international study, set up by investigators in the UK, Australia and Canada to explore if drugs already used to lower blood pressure (ACE inhibitors) and cholesterol levels (Statins) in adults with diabetes could reduce the risk of kidney, eye and cardiovascular disease in adolescents with Type 1 diabetes.

Neither ACE inhibitors nor statins significantly reduced the albumin-creatinine ratio during the 2-4 year trial period. However, some of the secondary outcomes suggest that the drugs may have important benefits.

Treatment with the ACE inhibitor resulted in a 43% reduction in the rates of progression to microalbuminuria, which was not statistically significant, but it could have important clinical implications. Preventing even intermittent cases of microalbuminuria is known to reduce the future risk of kidney and cardiovascular complications.

Statin therapy led to reduced levels of lipid levels, which could reduce long-term risk for cardiovascular complications.

These findings could translate into long-term benefits, but follow-up of this unique cohort will be essential. The essential biological samples and data provided by the participants will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes.

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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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Trying Statins Again After Adverse Effect Linked To Lower Risk of Heart Attack

MedicalResearch.com Interview with:

Alexander Turchin, MD,MS Director of Quality in Diabetes Associate Professor, Harvard Medical School Brigham and Women's Hospital Boston, MA

Dr. Turchin

Alexander TurchinMD,MS
Director of Quality in Diabetes
Associate Professor, Harvard Medical School
Brigham and Women’s Hospital
Boston, MA

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

Response: Cardiovascular disease is the # 1 cause of death in the U.S. and worldwide. Statins are some of the most effective medications available for prevention of cardiovascular events.

However, many patients stop statins, frequently because of adverse reactions. In our study we aimed to assess the risk-benefit balance of trying a statin again after experiencing an adverse reaction.

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May Be No Benefit To Statins For Primary Prevention in Older Adults

MedicalResearch.com Interview with:
Benjamin Han, MD, MPH
Assistant professor
Departments of Medicine-Division of Geriatric Medicine and Palliative Care, and Population Health
NYU Langone Medical Center

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

Response: There are an increasing number of older adults being prescribed statins for primary prevention, but the evidence for the benefit for older adults is unclear.

Our study finds that in the ALLHAT-LLT clinical trial, there were no benefits in either all-cause mortality or cardiovascular outcomes for older adults who did not have any evidence of cardiovascular disease at baseline.

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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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