FDA Approves New Indication For Altace (Ramipril), To Reduce Risk of Stroke, Heart Attack

MADISON, NJ — October 6, 2000 — American Home Products Corporation announced that Altace® (ramipril) received approval from the U.S. Food and Drug Administration (FDA) to reduce the risk of stroke, myocardial infarction (heart attack) and death from cardiovascular causes in patients 55 and over either with a history of coronary artery disease, stroke, or peripheral vascular disease or with diabetes and one other cardiovascular risk factor (e.g., elevated cholesterol levels, cigarette smoking, etc.).

Altace is marketed by Monarch Pharmaceuticals, Inc., a wholly-owned subsidiary of King Pharmaceuticals, Inc. and Wyeth-Ayerst Laboratories, the pharmaceutical division of American Home Products.

This new, expanded indication is based on evidence from the landmark HOPE study (Heart Outcomes Prevention Evaluation), in which 9,297 patients were evaluated for over four years. The independent Data and Safety Monitoring Board halted the five-year HOPE study one year early because of the clear evidence of the beneficial effect of Altace 10 mg. Patients included in the trial had normal or treated blood pressure. However, patients were excluded if they had heart failure or left ventricular dysfunction.

Rates of reduction of cardiovascular events reported from the HOPE study include 32 percent for stroke, 20 percent for heart attack, 26 percent for cardiovascular death, and 22 percent for all three endpoints combined. The effect of Altace 10 mg was evident after about one year of treatment. In this trial, Altace 10 mg also reduced the incidence of death from any cause by 16 percent. Patients taking cardiovascular medications such as aspirin, beta-blockers or lipid-lowering agents received benefit by adding Altace 10 mg to their cardiovascular treatment, regardless of whether their blood pressure was normal or treated.

“Millions of Americans suffer from one or more types of cardiovascular disease. Based on the findings of HOPE, we believe that if Altace is used in the appropriate patients, we could significantly reduce the number of strokes, heart attacks, and deaths from cardiovascular causes each year. This new indication for Altace could significantly transform the treatment of people at risk for stroke and cardiovascular disease,” says James Young, M.D. a primary U.S. investigator in the HOPE study from the Cleveland Clinic. “The results of the HOPE study send a clear message that we can do more to improve outcomes, even if we feel that we are adequately treating risk factors such as blood pressure and lipids.”

The importance of reducing the incidence of stroke cannot be under-appreciated. The direct and indirect cost of stroke to our nation is US$30 billion. “Stroke is the number one cause of disability in the United States and the number three cause of death,” says Edgar J. Kenton III, M.D., neurologist, American Stroke Association. “Stroke affects at least 600,000 Americans and some studies have shown that it is as many as 750,000. About 150,000 of those individuals die each year of stroke.” The HOPE study findings are a very important development in helping reduce the incidence of stroke, among patients aged 55 and over who have a history of cardiovascular disease.

In addition, for patients 55 and over with diabetes and at least one other cardiovascular risk factor, the HOPE study was the first of its kind to show that a specific treatment could reduce cardiovascular events in this specific diabetic population. The HOPE study evaluated 81 patients with type 1 and 3,496 patients with type 2 diabetes. The results in the subset of diabetes patients were similar to the overall findings, leading to an overall reduction of cardiovascular events by 25 percent in this diabetic population. Diabetes, which is a known risk factor for the development of cardiovascular diseases, afflicts 15.7 million people in the U.S. and is the sixth leading cause of death by disease in this country, according to the American Diabetes Association. Two thirds of people with diabetes mellitus die of some form of heart or blood vessel disease.

The participants in the HOPE study were randomized to receive 10 mg of Altace or placebo orally once a day for a mean duration of five years. The study examined the effects of Altace in reducing cardiovascular events among a broad range of patients with a history of coronary heart disease, peripheral vascular disease, or stroke. In addition, patients with diabetes and one other cardiovascular risk factor were also included in this study. The patients were studied in 267 centers in 19 countries around the globe. The OPE study was ended one year early because of the clear evidence of the beneficial effect of Altace 10 mg.

“Today’s action by the FDA reaffirms our confidence in the positive benefits Altace can offer to many thousands of patients each year,” says Philip de Vane, M.D., Vice President, Clinical Affairs and North American Medical Director for Wyeth-Ayerst Laboratories. “This expanded indication gives doctors an additional tool in the management of patients whose cardiovascular condition places them at risk for the devastating effects of stroke and heart attack.”

John M. Gregory, Chairman and Chief Executive Officer of King Pharmaceuticals, states, “The FDA’s approval provides an important contribution to public health in making our product, Altace, available for the reduction of cardiovascular deaths, heart attacks, and strokes among appropriate patients. This is very good news for those patients age 55 or older who are at risk for such cardiovascular events, the number one cause of death in the United States.”

Joseph M. Mahady, President Wyeth-Ayerst North America adds, “Wyeth-Ayerst and King will relaunch Altace in early November with over 2,000 sales representatives. We intend to tell physicians about the benefit Altace can provide to patients that they are already treating with needed risk reduction medications. Physicians now have an opportunity to do more for these patients by adding Altace.”

Altace, an angiotensin-converting-enzyme (ACE) inhibitor, was first approved by the FDA in 1991 for use in the treatment of hypertension and subsequently approved by the FDA for the treatment of congestive heart failure after a patient suffers from heart attack. Altace is the first and only ACE inhibitor to receive FDA approval to reduce the risk of stroke, myocardial infarction and death from cardiovascular causes in patients 55 and over either with a history of coronary artery disease, stroke, or peripheral vascular disease or with diabetes and one other cardiovascular risk factor (e.g., elevated cholesterol levels, cigarette smoking, etc.).

Common adverse events associated with Altace include: headache, dizziness, fatigue, dry cough. Rare cases of angioedema (swelling of throat) have been reported. It is contraindicated in patients who are hypersensitive to the product or have a history of angioedema related to previous treatment with an ACE inhibitor. When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, use of all ACE inhibitors should be immediately discontinued.