Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes

TY - JOUR

T1 - Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes

AU - Cannon, Christopher P

AU - Blazing, Michael A

AU - Giugliano, Robert P

AU - McCagg, Amy

AU - White, Jennifer A

AU - Theroux, Pierre

AU - Darius, Harald

AU - Lewis, Basil S

AU - Ophuis, Ton Oude

AU - Jukema, J Wouter

AU - De Ferrari, Gaetano M

AU - Ruzyllo, Witold

AU - De Lucca, Paul

AU - Im, KyungAh

AU - Bohula, Erin A

AU - Reist, Craig

AU - Wiviott, Stephen D

AU - Tershakovec, Andrew M

AU - Musliner, Thomas A

AU - Braunwald, Eugene

AU - Califf, Robert M

AU - IMPROVE-IT Investigators

AU - Sydow, Karsten

AU - Clemmensen, Peter

PY - 2015/6/18

Y1 - 2015/6/18

N2 - BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups.CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).

AB - BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups.CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).

KW - Acute Coronary Syndrome/drug therapy

KW - Aged

KW - Anticholesteremic Agents/adverse effects

KW - Azetidines/adverse effects

KW - Cardiovascular Diseases/epidemiology

KW - Cholesterol, LDL/blood

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Ezetimibe

KW - Female

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Simvastatin/therapeutic use

KW - Triglycerides/blood

U2 - 10.1056/NEJMoa1410489

DO - 10.1056/NEJMoa1410489

M3 - SCORING: Journal article

C2 - 26039521

VL - 372

SP - 2387

EP - 2397

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 25

ER -