The much awaited results of the IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) trial is finally out, and patients may soon experience improved outcomes with much lower cholesterol levels.
IMPROVE-IT was a randomized, controlled trial on 18,144 patients with acute coronary syndrome (ACS) aged 50 years or older. If the patients were not on statins, their low-density lipoprotein (LDL) cholesterol levels had to be at most 125 mg/dL. If they were on statins, their LDL level had to be atmost 100 mg/dL.
Around 13,000 patients included in the study had non-ST elevation myocardial infarction (NSTEMI) or unstable angina (UA). The rest had ST-segment elevation myocardial infarction (STEMI). All had at least one risk factor for future cardiovascular (CV) event (i.e., a previous myocardial infarction [MI], diabetes, peripheral artery or cerebrovascular disease, coronary disease in multiple arteries, or bypass surgery in the past).
Enrolled patients were randomized to receive 40 mg of simvastatin or 10/40 mg of ezetimibe/simvastatin. The primary endpoint was CV death, MI, hospital admission for UA, coronary revascularization at least 30 days after randomization, or stroke.
After a mean follow-up of 6 years, patients on ezetimibe/simvastatin therapy had a 6.4% lower risk of combined outcoimes. MI was reduced by 13%, and non-fatal stroke was lower by 20%. CV deaths were statistically similar. Additionally, those on dual therapy had a mean LDL of 54 mg/dL vs 69 mg/dL with statin alone. Number needed to treat was 50.
According to lead author Christopher P. Cannon, MD, FACC, professor of medicine at Harvard Medical School, "The study is the first to show that adding another non-statin drug to a statin to improve cholesterol levels can help patients with specific heart problems do better," said Cannon. "We took [dual therapy] patients from a clinically appropriate target LDL-C to even lower. We now have solid evidence that lower is good, and even lower can be even better," he adds.
Patrick T. O'Gara, MD, FACC, president of the American College of Cardiology, states, "The relative risk reduction was small over a long period of follow-up with a large number of high risk patients, but the number of patients needed to treat in order to reduce the incidence of the composite end point by 1 was 50." He added, "It is encouraging to note that there was no important safety signal with the use of ezetimibe in the trial." He highlighted that the results of this trial should not be extrapolated to low-risk patients or in the setting of primary prevention.