Varied origins of promising hypotheses in cardiovascular medicine

Conducting a major clinical-outcomes, randomized-controlled trial is both labor and resource intense. The hypotheses worthy of testing are derived from a variety of sources and then further developed in pilot, non-definitive studies. This article illustrates the breadth of sources from major epidemiologic studies underscoring the prognostic impact of elevated blood pressure and elevated cholesterol, observational studies showing the adverse impact of ventricular premature beats, as well as experimental studies demonstrating proposed mechanisms such as myocardial salvage and the attenuation of ventricular remodeling during myocardial infarction. In each case, the matter of how attractive the hypothesis, the safety and effectiveness of the proposed intervention requires robust clinical outcome trials.