Aspirin and ACE Inhibitors in Patients with Heart Failure: WATCHing for a Potential Interaction

Coronary artery disease is the leading cause of chronic heart failure and consequently a large proportion of patients with left ventricular (LV) dysfunction are treated with aspirin. Angiotensin-converting enzyme (ACE) inhibitors have emerged as the standard therapy for patients with both symptomatic and asymptomatic LV dysfunction. When the respective actions of these two agents with regard to prostaglandin synthesis are considered, the potential for an antagonistic interaction is evident. In a bradykinin-dependent mechanism, ACE inhibitors stimulate the synthesis of the vasodilator prostacyclin. Aspirin, a cyclooxygenase inhibitor, inhibits the production of prostaglandins. There is evidence that in patients with LV dysfunction, the favorable effects of ACE inhibitors on hemodynamic measures of systemic vascular resistance, cardiac output and LV filling pressures are significantly attenuated by the coadministration of aspirin. There is an accumulating body of retrospective clinical trial data suggesting that these hemodynamic influences translate into a reduction in the mortali- ty benefit seen in ACE inhibitor-treated patients not receiving aspirin. This review will address the mechanism of this potential interaction, as well as the hemodynamic and clinical trial data suggesting the relevance of this interaction. The Warfarin Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial, an ongoing study designed to address the issue of the appropriate antithrombotic therapy for patients with chronic heart failure will be discussed.