Combination therapy may reduce cardiovascular risk in chronic kidney disease patients

May 16, 2017 – A combination of simvastatin, a lipid lowering agent, and ezetimibe, an inhibitor of intestinal cholesterol, may benefit patients with moderately reduced kidney function, states a paper published today in the Journal of the American Society of Nephrology.

Chronic kidney disease (CKD) is a major public health problem that affects more than 20 million Americans, carrying an increased risk for death from cardiovascular disease, due to several factors such as malnutrition, chronic inflammation, increased oxidative stress, and vascular and endothelial dysfunction. Kidney function, as measured by estimated glomerular filtration rate, is an independent and strong predictor of this risk. However, CKD patients have historically been excluded from clinical trials, resulting in a limited understanding of the safety and efficacy of lipid modifying therapies in this population.

This post-hoc analysis examined data from 18,000 patients involved in the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). This was a multi-country, double-blind, randomized controlled study evaluating the effect of ezetimibe combined with simvastatin, compared with simvastatin alone, in individuals with known cardiovascular disease and baseline LDL (‘bad’) cholesterol values below 125 mg/dL.

“In our analysis, combination therapy with ezetimibe plus simvastatin appeared to be more effective than simvastatin monotherapy in reducing death from cardiovascular disease, major coronary events, or nonfatal stroke at moderately reduced levels of kidney function,” said lead author John W. Stanifer, MD, MSc. Stanifer is co-chief fellow at the DCRI and a fellow in the Division of Nephrology, Department of Medicine, Duke University. “These effects, seen over the seven years of the IMPROVE-IT study, could impact our ability to treat this high-risk population. However, further studies of combination lipid-lowering therapy in individuals with CKD are needed, particularly in those with more severely reduced kidney function.”

These findings are in line with those of the Study of Heart and Renal Protection (SHARP) study, which concluded that around a quarter of heart attacks, strokes, and operations to open blocked arteries could be avoided in people with chronic kidney disease by using the combination of simvastatin and ezetimibe to lower blood cholesterol levels. The SHARP study involved nearly 9,500 volunteers aged 40 or over with chronic kidney disease recruited from 380 hospitals in 18 countries.

Other Duke and DCRI authors on the paper were Jennifer White, MS; Yuliya Lokhnygina, PhD; Matthew T. Roe, MD, MHS; and Michael A. Blazing, MD.