FDA Approves ZOCOR 40 mg as Starting Dose for People at High Risk of Coronary Events because of Coronary Heart Disease or Diabetes

Business Wire, April 17, 2003

Business Editors/Health/Medical Writers

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--April 17, 2003

Merck & Co., Inc. (NYSE:MRK) announced today that the Food and Drug Administration (FDA) has approved changes to the prescribing information for ZOCOR(R) (simvastatin) to include results from the landmark Heart Protection Study with ZOCOR 40 mg, the largest cholesterol treatment study ever conducted.

As a result of the FDA's decision, ZOCOR 40 mg is now recommended, along with diet, as the starting dose for ZOCOR for people with coronary heart disease (CHD) or diabetes. ZOCOR 40 mg is the first and only cholesterol-lowering medication proven to reduce the risk of heart attack and stroke in people with heart disease or diabetes regardless of cholesterol level. Treatment with ZOCOR 40 mg as compared to placebo reduced the risk of death from any cause by 13 percent (ZOCOR 1328/10269 vs. placebo 1507/10267, p=0.0003).

"The new use has the potential to change the treatment approach of people with CHD and those with diabetes. It demonstrates that the millions of people who suffer from CHD or diabetes could benefit from treatment with simvastatin 40 mg known as ZOCOR," said

Alan J. Garber, M.D., Ph.D., chief of Endocrinology, Diabetes and Metabolism, The Methodist Hospital in Houston. "This news is particularly relevant in light of the latest NCEP Guidelines, which call for aggressive treatment of patients at high-risk for heart attacks such as people with diabetes or CHD."

ZOCOR 40 mg reduced the risk of non-fatal heart attack by 38 percent

The Heart Protection Study, conducted by the Clinical Trial Service Unit of world-renowned Oxford University, U.K., followed 20,536 people considered to be at high risk for a heart attack for five years. The study results demonstrated that ZOCOR 40 mg reduced the risk of non-fatal heart attack by 38 percent compared to placebo in people with heart disease or at high risk for heart disease, such as people with diabetes (ZOCOR 40 mg 357/10,269 vs. 574/10,267 for placebo, p<0.0001). The study also demonstrated that ZOCOR 40 mg reduced the risk of stroke by 25 percent (ZOCOR 40 mg 444/10,269 vs. 585/10267 for placebo, p<0.0001). In addition, the study demonstrated risk reductions in major coronary events* with ZOCOR 40mg in all high risk patient groups studied such as those with a history of heart attacks, diabetes or vascular disease including women and the elderly. Importantly, in patients at high risk of CHD, these results were consistent even in those patients whose cholesterol levels were not high enough to require drug treatment under current guidelines.

The recommended usual starting dose for ZOCOR is 20 to 40 mg once a day in the evening. For patients at high risk for a CHD event due to existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter. The prescribing information has additional information on dosing recommendations in special populations and with certain concomitant medications.

Patients in this study were 40 to 80 years old. Twenty-five percent (n=5,082) of the patients were women. Patients were at high risk of a major coronary event because of existing coronary heart disease, diabetes, history of stroke or other cerebrovascular disease, peripheral vessel disease or hypertension (males over 65 years). Patients had a range of LDL - the so-called "bad" - cholesterol levels. Seventeen percent (n=3421) had levels at baseline below 100 mg/dL (of whom 953 had LDL-C levels below 80 mg/dL); 34 percent (n=7,068) were between 100 mg/dL and 130 mg/dL, and the remaining 49 percent (n=10,047) had levels greater than 130 mg/dL.

ZOCOR 40 mg is the only statin proven to reduce the risk of heart attack and stroke in people with diabetes

The Heart Protection Study with ZOCOR 40 mg was the first study designed to investigate the benefits of ZOCOR 40 mg in people with diabetes with or without a prior history of heart disease or high cholesterol. The study included 5,963 people -- about 29 percent of all people in the study -- with diabetes (of all patients studied 26 percent had Type II diabetes and 3 percent had Type I diabetes). Compared to placebo, ZOCOR 40 mg reduced the risk of suffering one or more major coronary events by 27 percent (ZOCOR 40 mg 279/2978 vs. 377/2985 for placebo, p<0.0001) in people with diabetes with or without prior heart disease with the greatest effect seen in diabetic patients without CHD.

According to the National Institutes of Health's (NIH) new NCEP Guidelines, people with diabetes without heart disease have the same risk of having a heart attack as someone who has heart disease without diabetes. "The real problem is that the link between diabetes and heart disease is often misunderstood, underestimated or ignored. One survey found that more than two thirds of people with diabetes are unaware they face an increased risk of heart attack and stroke," said Dr. Garber. According to data from the United Kingdom Prospective Diabetes Study, the greatest predictor for coronary risk in people with Type II diabetes is high LDL cholesterol, followed by low HDL cholesterol, high blood sugar and high blood pressure. Dr. Garber commented, "So for people with diabetes, managing their risk factors for heart attack and stroke is as important as managing glucose." For physicians treating people with diabetes, the Heart Protection Study results support starting patients on ZOCOR 40 mg along with diet immediately upon diagnosis, regardless of their cholesterol or blood sugar levels.