P&S Journal: Winter 1997, Vol.17, No.1
New Calcium-Channel Blocker for Severe Heart Failure
A new calcium-channel blocker, amlodipine, does not increase the risk of death in patients with severe heart failure, according to a study published in the New England Journal of Medicine. The PRAISE (Prospective Randomized Amlodipine Survival Evaluation) study, led by Dr. Milton Packer, the Dickinson Richards Professor of Medicine, also found that amlodipine may help heart failure patients with normal coronary arteries.
The PRAISE findings are important in light of the ongoing controversy over the safety and efficacy of calcium-channel blockers (CCBs), which are widely prescribed to treat hypertension and angina. CCBs have been reported to increase the risk of heart attack, stroke, cancer, congestive heart failure, and sudden death, raising fears among patients and physicians around the world.
However, Dr. Packer notes, these reports have largely been based on retrospective, case-control studies. Such studies are useful in uncovering trends but the scientific community considers them among the weakest forms of evidence.
PRAISE, in contrast, is the first study of the effects of CCB on major cardiovascular events using the most highly regarded study design--the prospective, randomized, double-blind, placebo-controlled trial.
In the PRAISE trial, 1,153 patients with severe, chronic heart failure were randomized to receive either placebo or amlodipine for six to 33 months. The primary endpoints were hospitalization for a major cardiac event and death.
Forty-two percent of those taking the placebo suffered a non-fatal or fatal cardiovascular event, compared with 39 percent of those taking amlodipine. The difference between the groups was even greater when the endpoint of death was considered alone: 38 percent of the placebo group and 33 percent of the amlodipine group died during the trial. "The difference is not statistically significant," Dr. Packer notes, "but the trend is in the right direction."
To determine whether the effects of amlodipine may vary among people with different types of heart failure, the study subjects were divided into ischemic heart disease and non-ischemic heart disease. Among the patients with ischemic heart failure, no difference was seen between the placebo and amlodipine groups. However, among the non-ischemics, the combined risk of cardiac morbidity and mortality was 31 percent lower in the amlodipine group. The risk of mortality alone was 46 percent lower among those who took amlodipine. These differences were statistically significant in favor of amlodipine.
Dr. Packer, a longtime critic of CCBs, was surprised at the results. "For years and years, I wrote in the literature about how I thought these drugs were dangerous and shouldn't be used, particularly in high-risk patients," he says, "but now we have much more data on safety."
Nonetheless, Dr. Packer is not ready to endorse the use of amlodipine or any other CCB to treat heart failure. "These data indicate that amlodipine is safe, but they do not yet indicate that it is effective for the treatment of heart failure," he says.
Indeed, the researchers concluded, "Taken together, these observations indicate that amlodipine can be used with relative safety in patients with severe heart failure--an important finding, since angina and hypertension can be difficult to treat in patients with left ventricular dysfunction."
The researchers also noted, "Although amlodipine may reduce the risk of death in patients with non-ischemic dilated cardiomyopathy, we believe that such an effect requires confirmation in a second trial."
That trial, PRAISE 2, is now under way. About a dozen other prospective, randomized, double-blind, placebo-controlled trials of CCBs are in progress. "By the year 2000 or 2001, we will have much more information than we have now," says Dr. Packer.