Ezetimibe plus statin reduces cardiovascular event risk in high-risk patients with acute coronary syndrome: Featured at AHA 2014

by Bruce Sylvester: Treating high-risk, acute coronary syndrome (ACS) patients with both a stain and ezetimibe enhances prevention of heart attacks and strokes, researchers reported on Nov. 17, 2014 at the American Heart Association’s Scientific Sessions 2014.

“The study is the first to show that adding a non-statin drug to a statin to improve cholesterol levels can help patients with specific heart problems do better,” said Christopher Cannon, M.D., lead author and professor of medicine at Harvard Medical School, in Boston.

Researchers for the IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial), enrolled 18,144 subjects at 1,158 centers in 39 countries. Subjects had been diagnosed with ACS, were at least 50 years old and had low-density lipoprotein (LDL) cholesterol levels at 125 or lower, or at 100 or lower if they were using a statin prior to enrollment.

“The patients, enrolled within 10 days of hospitalization for a heart attack or unstable angina, were high risk,” Cannon said. About 5,000 of them had suffered a full-thickness heart attack known as an ST-segment elevation myocardial infarction, or STEMI. The remaining 13,000 had suffered a non-STEMI heart attack or had unstable angina, defined by new or worsening chest pain. Patients also had at least one feature putting them at high risk for a further cardiovascular event, including a previous heart attack, diabetes, peripheral artery or cerebrovascular disease, coronary disease in multiple arteries, or bypass surgery in the past.

They were treated with either 40 mg simvastatin/placebo daily or 10 mg ezetimibe/40 mg simvastatin daily. The researchers followed the subjects an average of about six years, and as long as 8.5 years.

The investigators reported that, compared to subjects with coronary heart disease receiving simvastatin plus a placebo, those treated with simvastatin plus ezetimibe achieved a 6.4 percent lower risk of all cardiovascular events, a 14 percent lower risk of all heart attacks, a 14 percent lower risk of stroke and a 21 percent lower risk of ischemic stroke. This translated into the finding that treating 100 patients for 7 years with dual therapy would prevent two cardiovascular events.

Mortality from cardiovascular disease was statistically the same for both cohorts.

Notably, dual therapy reduced LDL to an average of 54 mg/dL, compared with 69 for statin-plus-placebo subjects. “We took those 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,” Cannon said.

The investigators reported no increase in side effects with the addition of ezetimibe..

The manufacturer of Vytorin (simvastatin plus exetimibe), Merck & Co., supported the study.