The bumpy road to drug development for acute heart failure

The prevalence of heart failure (HF) continues to grow, in large part attributed to the aging population. Parallel to this trend is the increasing burden of hospitalization for worsening HF, which accounts for the majority of the very high societal burden of costs of care for these patients. These hospitalizations represent a change in the trajectory of the disease process and are associated with a significantly higher risk of adverse outcomes, a trend that has not changed over the past two decades. Although short-term readmissions are due to haemodynamic congestion, long-term prognosis and mortality are the result of the continuous deterioration of cardiac substrate, worsening of comorbidities, and progression of HF. Thus, when planning a new therapeutic intervention in acute HF, it is essential to have insight into the mechanism and temporal distribution of adverse outcomes. Furthermore, as acute HF patients die or are readmitted due to multiple reasons it is important to match the mechanism of action of the intervention to the mechanism of the adverse event. Despite many clinical trials to date in these patients, there currently is not a single agent that is known to improve post-discharge mortality risk in these patients. A variety of reasons have been offered to account for the lack of success in these clinical trials. A careful review of these previous experiences offers some significant insights into lessons learned and provides guidance for future novel intervention development for this growing patient population.