Combination therapy with angiotensin converting enzyme (ACE) inhibitors and nitrates in patients with heart failure may obviate the need for concomitant hydralazine, reduce nitrate tolerance and improve patient outcomes. These topics are the focus of a continuing medical education (CME) activity published June 3 in the JACC: Heart Failure.

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The article reviews the evidence for nitrate therapy in patients with heart failure, strategies for overcoming nitrate tolerance and clinical trial design for future studies of nitrate therapy in patients with heart failure. It also addresses the benefits and limitations of hydralazine therapy, ACE inhibitors' effects on nitrate tolerance and the available data on the effects of ACE inhibitors plus nitrates on hemodynamic function, exercise tolerance and left ventricular function.

"Despite proven benefits, combination hydralazine and nitrate therapy is not commonly used in heart failure. Multiple challenges are associated with hydralazine use," the authors wrote. "ACE inhibitors also provide the afterload reduction and nitrate tolerance benefits seen with hydralazine. Demonstrating benefit with nitrates and ACE inhibitors without concurrent hydralazine use may represent a major opportunity to improve nitrate therapy in heart failure."

Moving forward, the authors note that much more research into the long-term role of therapy with hydralazine and nitrates is needed, along with additional research into the combination of ACE inhibitors plus nitrates. They identify two important research questions: Does the combination of hydralazine plus nitrates improve outcomes in non-black patients with heart failure and do nitrate/ACE inhibitor combinations produce the same benefit as nitrate/hydralazine combinations?

Keywords: Exercise Tolerance, Drug Tolerance, Hydralazine, Ventricular Function, Left, Nitrates, Heart Failure, Hemodynamics

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