Unbelievable Folly of Clinical Trials in Heart Failure: The Inconvenient Truth About How Investigators and Guidelines Weigh Evidence.

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Despite significant advances in the treatment of chronic heart failure during the past 30 years, there is a broad consensus that new treatments are needed because morbidity and mortality in this disorder remain unacceptably high.1 Nevertheless, the development of new drugs for chronic heart failure has waned during the past 20 years; the quantity of novel agents in clinical testing and the number of well-designed clinical trials have diminished to a small fraction of that seen in the 1980s and 1990s.2 Some have suggested that investment in heart failure has declined because the primary mechanisms of the disorder are poorly understood, because the promising results of phase II trials are frequently not confirmed in large-scale definitive studies, and because the large-scale clinical trials needed for regulatory approval have often become prohibitively expensive.2,3 We know that clinical research in heart failure is extremely challenging, and so we beg innovators in the pharmaceutical and device industries to be patient, and we plead with sponsors to invest in large-scale investigations because the need is so great. Yet, when we critically examine how we react to data, it may not be too surprising that meaningful clinical trials in heart failure are becoming increasingly scarce.2 Do cardiologists act as if the results of clinical trials in heart failure really matter? Most heart failure trials yield results that are disappointing or difficult to interpret. Yet, such studies would nevertheless be enormously useful if we learned from these setbacks and moved on. But do we? At the 2015 Scientific Sessions of the American Heart Association, every randomized trial in heart failure presented in the late-breaking sessions yielded distressing results. A phase II trial of the soluble guanylate cyclase stimulator vericiguat failed to meet its primary end point, even though the change …