Pharmacologic treatment of chronic systolic heart failure: Past, present, and future

PURPOSE: To review the pharmacologic management of chronic systolic heart failure (HF). EPIDEMIOLOGY: Approximately 550 000 new cases of HF are diagnosed each year with a mortality rate of 20.1 per 100 000 population. REVIEW SUMMARY: Early clinical trials in HF focused on the use of inotropic and antiarrhythmic agents for the most common modes of mortality in chronic systolic HF: progressive pump failure and sudden cardiac death. The fact that these agents not only failed to improve survival but actually increased mortality led to an improved understanding of the neurohormonal compensatory mechanisms operative in HF. This, in turn, led to the current concept that interrupting these compensatory mechanisms improves outcomes in chronic HF. TYPE OF AVAILABLE EVIDENCE: Unstructured review, randomized-controlled clinical trials, cohort studies, case series. GRADE OF AVAILABLE EVIDENCE: Good. CONCLUSION: Early clinical HF trials aimed at reducing direct modes of mortality in HF. Presently, HF trials are chiefly focused on antagonizing the neurohormonal compensatory mechanisms activated in this disorder. Future therapeutic interventions may be directed at strategies to avoid activation of the neurohormonal system altogether.