Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function.

Abstract

Efficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2 Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30-60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1681/ASN.2016090957

Publication Info

Stanifer, John W, David M Charytan, Jennifer White, Yuliya Lokhnygina, Christopher P Cannon, Matthew T Roe and Michael A Blazing (2017). Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney Function. J Am Soc Nephrol, 28(10). pp. 3034–3043. 10.1681/ASN.2016090957 Retrieved from https://hdl.handle.net/10161/15967.

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Scholars@Duke

Stanifer

John W. Stanifer

Adjunct Assistant Professor of Medicine

John W. Stanifer, MD, MSc-GH, is a nephrologist and clinical researcher with a focus on using translational and trans-disciplinary methods to uncover mechanisms of global health disparities in kidney disease. John completed his residency training in internal medicine and global health at Duke, completing the Master of Science in Global Health program in 2014. He also completed his sub-specialty training in nephrology at Duke, and during that time, he also completed a fellowship in clinical research at the Duke Clinical Research Institute, where he served as chief fellow in 2016-2017.

He has investigated the epidemiology of chronic kidney disease in Tanzania, where he started and led the CKD-AFRIKA study. This mixed-method study not only was among the first to explore community-based prevalence, risk factors and consequences of chronic kidney disease in sub-Saharan Africa, but it also investigated several cultural and social topics around the use of traditional medicines among individuals living with kidney disease.

More recently, he has also turned his attention to local health disparities. Since 2015, he has been co-leading, with Dr. Cherry Beasley, the KIDNEY NC Study, a mixed-methods study investigating determinants of kidney disease among ethnic and racial minorities in Robeson County, North Carolina, home of the Lumbee Indian tribe. In addition to a Bass Connections team, he and Dr. Beasley have led two Student Research Training programs that included several Duke students working in Robeson County each summer. He is mentored by Drs. L. Ebony Boulware and Myles Wolf.

Lokhnygina

Yuliya Vladimirovna Lokhnygina

Associate Professor of Biostatistics & Bioinformatics

Statistical methods in clinical trials, survival analysis, adaptive designs, adaptive treatment strategies, causal inference in observational studies, semiparametric inference

Roe

Matthew Todd Roe

Adjunct Professor in the Department of Medicine

My clinical activities focus upon general, preventive, and acute care cardiology.  I round regularly on the inpatient general cardiology and coronary care unit (CCU) services and i have a particular interest in the treatment and management of patients with acute myocardial infarction and cardiogenic shock.  In my outpatient clinic, I care for patients with a variety of cardiovascular conditions include chronic coronary artery disease, hypertension, hyperlipidemia, atrial fibrillation, congestive heart failure, aortic aneurysms, and peripheral arterial disease.  In this setting, I have a particular interest in cardiovascular risk factor modification and long-term treatment strategies to mitigate the risk of future cardiovascular events.

My research activities at the Duke Clinical Research Institute focus upon the coordination and leadership of randomized clinical trials evaluating new therapies for a variety of cardiovascular conditions (acute myocardial infarction, hyperlipidemia, coronary stent placement, peripheral arterial disease, and coronary artery disease) as well as observational registries that evaluate the same disease conditions.

Blazing

Michael August Blazing

Associate Professor of Medicine

General focus: My research interests are in primary and secondary prevention of cardiovascular disease. Specifically, I am looking at compliance issues within the cardiology division and in the University as a whole with regard to evidence based treatment and secondary prevention of cardiovascular disease. I am using both retrospective and prospective collection of discharge data to try and analyze these trends. In the future, we hope to begin clinical trials with regard to various issues which are outstanding in primary and secondary prevention. Some of the issues include treatment of hypercholesterolemia in elderly patients, differences between the various statins with regard to affects on lipid profiles, and early treatment of hypercholesterolemia after MI.

As part of my work, I have served as a consultant with various drug companies with regard to focusing on active issues and treatment of hypercholesterolemia.

Key words: Primary prevention, secondary prevention, hyperlipidemia, homocysteine, and hypertension.


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