Drugs for Heart Failure

Assessing a drug for efficacy and safety in heart failure is a challenging task (Guyatt, 1986). For example, six compounds have been considered by the US Food and Drug Administration (FDA) during the 1980s: captopril, enalapril, amrinone, milrinone, lisinopril and isosorbide dinitrate. However, only two (captopril and enalapril) have been approved for oral use in chronic heart failure. The chief difficulties have been: (1) inability to define the optimal dose and dose interval; (2) inability to demonstrate a statistical superiority over placebo or a comparative agent; and (3) assessment of adverse effects and the impact of a drug on the natural course of a fatal disease (Packer and Leier, 1987).