The lower the better - the IMPROVE-IT study confirmed the importance of lowering cholesterol by ezetimibe

Background: The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit

for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in

patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) ≤125 mg/dL.

Methods: Randomized double blind clinical trial in patiens with acute coronary syndrome and low cholesterol level. The simvastatin

monotherapy arm‘s LDL-C target was <70 mg/dL, the comparison arm was simvastatin + ezetimibe. Ezetimibe was assumed to further

lower LDL-C by 15 mg/dL and produce an estimated ~8 % to 9 % treatment effect. The primary composite end point was CV death, nonfatal

myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization (≥30 days

postrandomization). The targeted number of events was 5 250.

Results: 18 144 patients were enroled with either ST-segment elevation MI (STEMI, n = 5.192) or UA/non-ST-segment elevation MI (UA/NSTEMI,

n = 12 952) from October 2005 to July 2010. Primary endpoint occured in 2742 patients (34.7 %) treated with simvastatin in monotherapy and

in 2 572 patients (32.7 %) (p = 0.016) treated with combination. Compared to patients with coronary heart disease given the drug simvastatin

plus a placebo, those given both simvastatin and the non-statin drug, ezetimibe, had a 6.4 percent lower combined risk of subsequent heart

attack, stroke, cardiovascular death, rehospitalization for unstable angina and procedures to restore blood flow to the heart. Heart attacks

alone were reduced by 13 percent, and non-fatal stroke by 20 percent. Deaths from cardiovascular disease were statistically the same in

both groups. Patients were followed an average of approximately six years, and some as long as 8.5 years. Approximately 2 patients out of

every 100 patients treated for 7 years avoided a heart attack or stroke. (Number Needed to Treat (NNT) = 50/7years).

Conclusions: The study has shown a clear benefit from combination treatment with simvastatin and ezetimibe in patients with acute

coronary syndrome and low LDL-C.

Keywords: acute coronary syndrom, LDL cholesterol, combination therapy, ezetimibe