Study: Ezetimibe Plus Statin Works

Can cholesterol get too low? Results from a multicenter international study called IMPROVE-IT show that adding ezetimibe to a statin regimen lowered cholesterol without harmful side effects in patients with acute coronary syndrome.

Results from a multicenter international study called IMPROVE-IT show that adding ezetimibe to a statin regimen is another weapon in the arsenal for patients with acute coronary syndrome. The new ezetimibe/simvastatin combination drug is manufactured by Merck and marketed as Vytorin.

Reporting at the American Heart Association’s Scientific Sessions in Chicago, IL, Christopher P. Cannon, MD, a professor of medicine at Harvard Medical School and physician at Brigham and Women's Hospital, and colleagues said the drug also lowers cholesterol—but by different means.

When patients in the study got simvastatin plus ezetimibe they had a 6.4% lower risk of all cardiovascular events, a 14% lower risk of all heart attacks, a 14% lower risk of stroke, and 21% lower risk of ischemic stroke.

But deaths from cardiovascular disease were about the same in the treatment group and a group that got the statin with placebo.

The study, the full name of which is “IMProved Reduction of Outcomes: Vytorin Efficacy International Trial,” was done at 1,158 centers in 39 countries. It enrolled 18,144 patients age 50 years or older with ACS and low-density lipoprotein (LDL) cholesterol levels at or less than 125—or at or less than 100 if they were already using a statin.

Patients were followed an average of approximately 6 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.

“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 Cannon,

In the study, patients enrolled within 10 days of hospitalization for a heart attack or unstable angina, were considered at high risk, Cannon said. About 5,000 of them had an ST-segment elevation myocardial infarction (STEM). 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.

Statins, such as simvastatin, block cholesterol production in the liver, while ezetimibe, a cholesterol absorption inhibitor, reduces the body’s absorption of cholesterol in the intestine. In the study, the dual therapy reduced patients’ LDL to an average of 54 mg/dL, compared with 69 for those treated with the statin and placebo.

“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,” he said.

The addition of ezetimibe (which got FDA approval in 2002) did not raise patients’ risk of ill effects, such as liver or muscle problems, or cancer. Cannon said. Over a decade ago, researchers from the TIMI Study Group, based at Brigham and Women’s Hospital demonstrated that a high dose statin, which lowered cholesterol further than a regular dose statin, provided better clinical outcomes. The study proves that reducing cholesterol still more is beneficial to these patients, he said.

The study was funded by Merck.