Nitrate therapy for heart failure: benefits and strategies to overcome tolerance.

Combination therapy with hydralazine and nitrates can improve outcomes in patients with heart failure and low ejection fraction. However, this combination is underused in clinical practice for several reasons, including side effects related to hydralazine and polypharmacy. Some of the benefits seen with hydralazine, including afterload reduction and attenuation of nitrate tolerance, have also been observed with angiotensin-converting enzyme inhibitors. Demonstrating similar clinical benefits with nitrates plus angiotensin-converting enzyme inhibitor therapy alone, in the absence of hydralazine, may represent an opportunity to improve heart failure care by increasing the use of nitrates. In this paper, we summarize data that support studying such an approach.