Effect of nitrates on myocardial remodeling after acute myocardial infarction

Nitrates are effective for the therapy of acute coronary syndromes, including acute myocardial infarction. Their application in acute infarction has established that vasodilators are beneficial provided hypotension is avoided. Nitrates limit early ventricular remodeling in infarction. New dosing strategies and formulations that permit chronic use after infarction with less tolerance might limit late remodeling. Over the last decade, the demonstrated effectiveness of angiotensin-converting enzyme (ACE) inhibitors in limiting ventricular dilation postinfarction has generated controversy over the usefulness of nitrates for that indication. The uncertainty has been intensified by 2 large mortality trials that tested both agents as adjuncts to conventional therapy. These trials were not designed to test whether nitrates might limit remodeling. Mechanistic experimental and clinical studies that tested whether nitrates or ACE inhibitors could effectively limit ventricular remodeling showed that both improved remodeling endpoints. However, experimental studies raise some concern about the decrease in infarct collagen associated with ACE inhibition and emphasize the fact that final outcome represents a balance of effects. That nitrates do not decrease infarct collagen could be important. Nitrate-induced early recruitment of ventricular function after late reperfusion of acute infarction might also be important. In the mortality trials, >50% of patients received open-label nitrates as per indication. Thus, the trial results to date do not suggest that nitrates are ineffective for remodeling, but rather that ACE inhibitors can confer added benefit. There has been no large clinical trial to test the efficacy of nitrates for remodeling as there has been for ACE inhibitors.