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| |  Norvasc Demonstrated to be Safe in Sickest Heart Patients NEW YORK, Oct. 9, 1996 -- A major study published in the New England Journal of Medicine this week demonstrated that the Pfizer long-acting calcium channel blocker Norvasc (amlodipine) is safe even in the most severely ill congestive heart failure patients, the company announced. "The PRAISE trial clearly demonstrates that Norvasc, already shown safe and effective in treating hypertension and angina in the general population, is safe even in the sickest cardiac patients -- those with Class III and IV congestive heart failure," said Roger Sachs, M.D., senior vice president for medical affairs for Pfizer Inc. The Prospective Amlodipine Survival Evaluation (PRAISE) trial also showed that in one group of patients, Norvasc patients had a 31 percent lower risk of a cardiac event and a 45 percent lower risk of death. To further investigate this promising finding, a second trial known as PRAISE II has begun. "Treating hypertension and angina in patients who also have CHF represents a difficult clinical challenge because there are only limited numbers of drugs that can be safely used in this extremely ill patient population," Dr. Sachs said. "The results of PRAISE now give physicians an important new treatment option." Congestive heart failure (CHF) is a complex, clinical syndrome that is characterized by severe illness and death. Affecting about 1 percent of the U.S. population, CHF is a rapidly growing disease with about 400,000 new cases each year. Its prevalence is increasing as the U.S. population ages. The multi-center safety PRAISE trial was directed by Dr. Milton Packer, director of Heart Failure Research at Columbia-Presbyterian Medical Center, and included 1,153 patients with severe congestive heart failure. All PRAISE patients received the currently recommended treatment of a diuretic, digoxin, and an angiotensin converting enzyme inhibitor. In addition, the patients were randomly divided into two groups: one received Norvasc and one received placebo. The study evaluated the effect of Norvasc on death and serious cardiovascular events such as the incidence of myocardial infarction (heart attack) during the 34 month trial. The study showed that Norvasc had no adverse effect on the mortality or exacerbation of disease for any group of patients. In addition, in a group of patients with CHF of non-ischemic origin, Norvasc significantly lowered the rate of death and illness. (Ischemia results from poor oxygen supply to the heart.) Again directed by Dr. Packer, the PRAISE II trial will include 1,800 patients in the U.S. and Canada. "The methodology in both PRAISE trials achieves the gold standard in medical research: prospective, randomized, double blind and placebo controlled with the correct statistical approach," Dr. Sachs said. "As such, the PRAISE trial gives clinicians real insight into the effects of Norvasc in patients with CHF." In addition to the PRAISE trial, Norvasc is being evaluated in three major completed or ongoing National Institutes of Health trials. In the TOMHS trial, Norvasc patients were more likely to continue on their medication compared to patients on other anti-hypertensives. Two other trials known as ALLHAT and AASK are also underway. Norvasc, among the most widely prescribed anti-hypertensives in the world, has a unique safety and efficacy profile. Norvasc reduces blood pressure gradually, has a long half life, and produces a smooth consistent effect in blood pressure control. Pfizer Inc. is a research-based, diversified health-care company with global operations. The company reported sales of approximately $10 billion for 1995, and plans to invest about $1.7 billion on research and development this year. To accompany a Pfizer Inc. news release about the publication of PRAISE study in the New England Journal of Medicine Pfizer today issued the following: The PRAISE Results and the Calcium Channel Blocker Controversy: Qs and As Q1) What makes the PRAISE study different from the other studies that have created a controversy over the safety of the calcium channel blockers? A1) Because PRAISE is a large-scale, prospective, randomized, well-controlled clinical trial, physicians can have confidence that the hypothesis that generated the trial has been meaningfully answered. There is no ambiguity about the PRAISE data: Norvasc has been demonstrated safe for use in classes 3 and 4 congestive heart failure patients. In addition, preliminary evidence that patients with CHF of non-ischemic origin experience fewer deaths or cardiac events when treated with Norvasc is now being further explored in a follow-up trial known as PRAISE II. These two PRAISE trials represent the best kind of medical research and stand in sharp contrast to a series of small, highly controversial retrospective analyses that have questioned the safety of older, short-acting CCBs, which are taken three or four times a day by patients. These older agents are approved only for treatment of chest pain, not high blood pressure, like the more modern CCBs. During the past 18 months, these small studies were heavily publicized and unnecessarily alarmed patients and physicians. An expert panel convened by the U.S. Food and Drug Administration examined all relevant data and, in January, concluded that product labeling should be clarified for short-acting nifedipine to limit uses of the drug in medical conditions for which it is not approved. The panel raised no safety issues for the modern-long acting CCBs. In short, PRAISE offers patients and physicians solid evidence that the long-acting calcium channel blocker Norvasc is safe for use in the most severely ill cardiac patients. Q2) Should amlodipine be used to treat congestive heart failure? A2) Norvasc is approved to treat high blood pressure and angina. It can be used to treat those conditions in CHF patients but not CHF itself. These results do mean that physicians can continue to use Norvasc to control high blood pressure or angina in patients who subsequently develop CHF. Q3) What about cancer scares and CCBs? A3) As in the cardiovascular issues discussed in A1, the cancer issue has been raised through retrospective analyses from data bases that were not constructed to evaluate cancer rates. The patients in the two groups were not comparable and many well-known studies show that pre-existing conditions can influence a physician's selection of medication. While not a primary endpoint of the PRAISE study, investigators found no increased cancer rates among amlodipine patients compared with those receiving placebo. Q4) How many patients are being treated with Norvasc? A4) The widespread clinical acceptance of Norvasc is supported by the more than 4 billion patient days of therapy for the drug since introduction. Currently, Pfizer estimates that approximately 5 million patients are being treated with Norvasc. Q5) Does publication of the PRAISE study resolve the CCB controversy? A5) The PRAISE study is about one drug -- Norvasc -- and its results cannot be extrapolated to any other drug. CCBs are clearly a diverse class of drugs sharing one mechanism. During the past three decades, their value in combating cardiovascular disease has been well-established. Nevertheless, the widespread publicity given to several retrospective analyses during the past 18 months has produced numerous news articles that lump together very different drugs into a single CCB group. Although the studies themselves produce different findings among various CCB drugs, the news coverage has simplified a complex medical issue to the point where patients and physicians are confused. In this broader context, the following points may be made in regard to the PRAISE study: It is a safety study in which the long-acting CCB Norvasc was tested among the sickest patients. The results unequivocally show that the drug is safe. The methodology of the trial is superior to the retrospective analyses. The PRAISE results add to the growing safety data surrounding calcium channel blockers. Recently published studies include the STONE study, which was a prospective trial showing that calcium channel blocker nifedipine significantly reduced the numbers of strokes. Also, an 11,575 patient data review, published in the Journal of the American College of Cardiology, showed the safety of calcium channel blockers was equivalent to other anti-hypertensives. A major hypertension review recently published in Patient Care concludes: "There are good data suggesting the long-acting calcium channel blockers may be as safe as other antihypertensive agents. The trick is to match the needs of the patient with the drug that most effectively reduces blood pressure and is well-tolerated. While not always the best choice, calcium channel blockers are an excellent treatment option for many patients."
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