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.

Ezetimibe and Improving Cardiovascular Outcomes: Current Evidence and Perspectives

“…Based on this strong results from this trial, 2013 ACC/AHA guidelines endorsed the use of ezetimibe patients with eGFR <60 ml/min [ 24 ]. Data from the IMPROVE-IT study mirrored similar findings [ 25 ]. Out of a total 18,144 patients, 3791 had eGFR <60 ml/min.…”

Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study

“…According to the most recent guideline for lipid management, 88% of patients who participated in the GCKD study would fulfil criteria for statin prescription [28]. Recent studies also suggested an additional benefit of dual treatment with ezetimibe with decreasing GFR [26, 29]. Implementation of this evidence would further increase medication load and polypharmacy prevalence.…”

Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study

“…17 In a post-hoc analysis of the randomized trial IMPROVE-IT, comparing participants randomized to simvastatin and ezetimibe versus simvastatin alone, the hazard ratios for the primary endpoint of cardiovascular death, major coronary event, or nonfatal stroke were 0.88 (95% CI: 0.82, 0.95) and 0.87 (95% CI: 0.78, 0.98) at eGFR levels of 60 and 45 mL/min/1.73 m 2 , respectively. 18 In the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, J o u r n a l P r e -p r o o f participants taking a statin who were randomized to PCSK9i had a lower risk for the primary endpoint of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization compared with their counterparts randomized to placebo (hazard ratio: 0.85; 95% CI: 0.79, 0.92). 19 There was no evidence supporting a difference in the hazard ratios between participants with eGFR ≥90, 60 to 89, and <60 mL/min/1.73 m 2 : 0.82 (95% CI: 0.71, 0.94), 0.85 (95% CI: 0.77, 0.94) and 0.89 (95% CI: 0.76, 1.05), respectively (p-interaction =0.75).…”