The early administration of nitrates in acute myocardial infarction (AMI) may lower myocardial oxygen demand and increase blood supply to the ischemic myocardium. Actually, nitrates are the drugs most largely used in AMI patients, but no definite proof of their clinical benefits had been reported before GISSI 3 and ISIS 4. Only a metaanalysis of several trials carried out before the thrombolytic era showed that intravenous nitrates and probably oral nitrates can reduce mortality when given early to patients with myocardial infarction. The adjunctive benefit of nitrates in AMI patients receiving the treatments recommended today (thrombolysis, aspirin, beta-blockade) remained undefined. Accordingly, two large controlled randomized studies - GISSI 3 and ISIS 4 - were undertaken to verify benefits and risks of nitrate strategy vs ACE-inhibition strategy in AMI. Overall, about 80,000 patients were enrolled. In both studies a small, non significant decrease of mortality was observed in patients allocated to nitrate arms. In GISSI 3, the mortality reduction was greater in patients receiving both nitroglycerin and lisinopril. Either intravenous or by oral or transdermal route nitrates were
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