Can physicians always explain the results of clinical trials? A case study of amlodipine in heart failure.

A lthough much emphasis is currently placed on evidence-based medicine, most of the decisions made in clinical practice are not based on data derived from randomized clinical trials. Perhaps this is to be expected, because it is impossible to conduct a trial to test the validity of every possible option available to physicians in the management of patients. Many therapeutic choices are so compelling that a test would be unethical; others are so trivial that a test might not be worth the time or effort. Yet, we cannot escape the fact that physicians do not practice evidence-based medicine even when evidence is available from randomized clinical trials. To most physicians, knowing the right answer is only the first step in the process of adopting a new treatment. They will not use a drug simply because they have seen data that indicate that it works; they will use the drug only when they have been told how it works. Indeed, for some, identification of the probable mechanism of action is the only prerequisite for adopting a new treatment. Such physicians will use a drug simply because it should work, even if there is no evidence that it does. The search for mechanisms has, in fact, emerged as a national preoccupation in the medical community. On the one hand, we will prescribe drugs that make mechanistic sense even if they are harmful; simply look at the enthusiasm for positive inotropic drugs for the treatment of chronic heart failure. On the other hand, we will avoid drugs that conflict with any preexisting view we might have of a disease even when the data supporting their use are overwhelming; witness, for example, the reluctance of physicians to prescribe b-blockers for the treatment of heart failure. The search for mechanisms drives (and haunts) all physicians, including those in academic medicine (who pride themselves on being rational) and those in primary-care medicine (who pride themselves on being practical). When the results of a clinical trial conflict with a widely held mechanistic model, we doubt the evidence from the study. When the results from clinical trials become so pervasive that they can no longer be ignored, we create and embrace a new model and forget the details of the trials. In the end, only the model survives. This should not be surprising: physicians are just like everyone else—we love a good story. The story of this supplement begins in March 1995. The results of a large-scale clinical trial known as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) study had just been presented at the Annual Scientific Sessions of the American College of Cardiology. The trial had randomized 1,153 patients with severe heart failure due to ischemic and nonischemic cardiomyopathy to treatment with placebo or amlodipine—with the intention of evaluating the long-term effect of the drug on morbidity and From the Division of Circulatory Physiology, Columbia University College of Physicians and Surgeons, New York, New York, USA (MP); and the Division of Cardiology, University of Florida Health Sciences Center, Jacksonville, Florida, USA (ABM). Address for reprints: Milton Packer, MD, Division of Circulatory Physiology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032.