The challenge of drug development in acute heart failure: balancing mechanisms, targeting patients, and gambling on outcomes.

Nearly 40 years ago, recommendations to treat acute heart failure (AHF) included oxygen, diuretic agents, vasodilators, and inotropes (1). Although the addition of rotating tourniquets and phlebotomy have become historical footnotes, a clinician treating AHF today would essentially use the same therapeutic modalities. A layperson might conclude that significant reductions in morbidity and mortality over time have obviated the need for improvements in medical therapy. Unfortunately, the statistics are much more sobering. With >1 million AHF hospital stays annually in the United States, death and rehospitalization rates after discharge remain unacceptably high, affecting 30% to 40% of patients within 90 days (2,3). At 1 year after discharge, nearly one-third of patients have died. Remarkably, the last drug approved to treat AHF was nesiritide in 2001, but the evidence for efficacy was modest at best, and the benefits were overstated and oversold. The need for new therapies to improve outcomes is unquestionable.