FDA clears new indication for DuPont Merck's Coumadin; 1st anticoagulant to reduce long-term mortality for heart attack survivors.

WILMINGTON, Del.--(HealthWire)--June 14, 1995--The U.S. Food and Drug Administration (FDA) has cleared for marketing DuPont Merck's Coumadin(R) (Warfarin Sodium) for a new indication -- the treatment of patients who have had a heart attack (myocardial infarction, or MI) to reduce the risk of death, a subsequent MI, and thromboembolic events, such as stroke.

Coumadin is one of the most frequently prescribed cardiovascular drugs in the United States, and its efficacy has been well established in the prevention and treatment of a variety of blood clotting disorders. The new indication makes Coumadin the first anticoagulant effective and safe for use in the reduction of long-term mortality for heart attack survivors. Coumadin therapy must be carefully monitored and reviewed by physicians to minimize the possibility of bleeding.

"This marks a significant advance in preventive therapy for heart attack patients," said Kurt Landgraf, president and chief executive officer, DuPont Merck. "In recent years, researchers have made great strides in our understanding of the significant role of clotting disorders and their serious consequences, including heart attacks, deep-vein thrombosis and pulmonary embolism, and thromboembolic stroke associated with atrial fibrillation. As Coumadin has demonstrated its safety and effectiveness in many thromboembolic conditions, we are confident the new indication will expand its usefulness to many other patients at risk."

The past decade has been a watershed in the treatment of heart attacks in the acute-care setting. The benefits of early administration of the so-called "clot-buster" drugs, such as tissue plasminogen activator and streptokinase, in reducing mortality in the period immediately following MI have been demonstrated repeatedly. However, patients remain at risk for future events once they leave the hospital.

Indeed, illness and death due to heart attacks are high. Each year, more than 1.5 million Americans suffer an MI. About 16 percent will die before reaching a hospital. Overall, 27 percent of men and 44 percent of women will die within one year after the first onset of symptoms. In the four years following a heart attack, 20 percent of women and 16 percent of men will be struck by a second MI.

Data Review

In clearing Coumadin (Warfarin Sodium) for the new indication, the FDA reviewed efficacy and safety data from two placebo-controlled studies, WARIS (Warfarin Reinfarction Study) and ASPECT (Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis), and a meta-analysis of 14 other previously published studies. The WARIS trial demonstrated that warfarin lowers the risk of death, reinfarction, and thromboembolic stroke in patients who have had a heart attack. ASPECT and the meta-analysis further support the use of oral anticoagulants in this population. Data gathered from the trials reviewed for this indication were obtained from more than 10,000 patients worldwide who were evaluated for periods of up to seven years.

The most common side effect of oral anticoagulation is bleeding. Studies have shown that the incidence of bleeding is related to the intensity of anticoagulation. The results of the clinical trials reviewed by the FDA demonstrate that the antithrombotic benefits of oral anticoagulation therapy outweigh the risks of major bleeding, and do so consistently across all studies.

The objective of anticoagulant therapy is to control the coagulation mechanism so that thrombosis is prevented, while avoiding spontaneous bleeding. Maintaining effective therapeutic levels with minimal complications is, in part, dependent upon cooperative and well-instructed patients who communicate effectively with their physicians.

The role of thrombosis in the genesis of heart attacks has become clearer in recent years. Two interrelated biochemical processes appear to be involved in clot formation: the activation of platelets and the initiation of the blood coagulation cascade. Clots are composed of fibrin, platelets, and red blood cells, in varying proportions. Coumadin (Warfarin Sodium) limits the formation of fibrin, a primary component of nearly all clots, by inhibiting the synthesis of vitamin K-dependent clotting factors, which are formed in the liver. Aspirin interferes with the clumping of platelets, which usually occurs in arteries, and may inhibit the formation of clots in which platelets dominate.

Physicians need to determine the appropriate use of Coumadin or aspirin for their patients. In patients thought to be at an increased risk of bleeding complications or on aspirin therapy, maintenance of Coumadin therapy at the lower end of the therapeutic range is recommended.

"Those patients who have had a heart attack are at the highest risk of another MI," said Valentin Fuster, M.D., Ph.D., director of the Cardiovascular Institute, Mount Sinai Medical Center, New York, and study chairman of CARS (Coumadin Aspirin Reinfarction Study). "We are hopeful that the long-term benefits of preventive therapy with Coumadin will be another strategy to reduce the morbidity and mortality associated with heart attacks and improve the odds for patients."

Coumadin should not be used in women who are or may become pregnant, patients with unsupervised dementia or certain other phychoses, and in other conditions in which the risk of trauma with bleeding exceeds the clinical benefit of anticoagulation.

Coumadin (Warfarin Sodium) is a product of The DuPont Merck Pharmaceutical Company, marketed under the DuPont Pharma Banner. DuPont Merck is a worldwide, research-based pharmaceutical company. Formed in 1991 as a partnership between DuPont and Merck and Co., DuPont Merck is focused on research, development and delivery of pharmaceuticals to treat unmet medical needs in the fight against cardiovascular, central nervous system and inflammatory diseases, cancer, and AIDS. The company also is a leader in radiopharmaceuticals.

CONTACT: Laura Mastrangelo, 302/892-8453

Steven Marks, 312/988-2348