Home > General Cardiology, Journal Club > Journal Club 8 July 2015

Journal Club 8 July 2015


Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes





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.


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.


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.


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.

Supplementary Material

The editorial is available here.

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