Six-month effects of early treatment with lisinopril and transdermal glyceryl trinitrate singly and together withdrawn six weeks atter acute myocardial infarction: The GISSI-3 trial

OBJECTIVES: This 6-month follow-up analysis sought to assess whether the early reduction of mortality obtained with a 6-week treatment course of lisinopril or glyceryl trinitrate, or both, in unselected patients with acute myocardial infarction outlasts therapy and is still present after 6 months. The primary outcome of the 6-month follow-up was the combined end point of mortality and severe left ventricular dysfunction. BACKGROUND: The assumption was that the early benefit on remodeling processes may be maintained over a longer period of time, even in the absence of treatment. METHODS: A total of 19,394 patients with acute myocardial infarction were randomized within 24 h of onset of symptoms to a 6-week treatment course of oral lisinopril or open control and, according to a 2 x 2 factorial design, to glyceryl trinitrate or open control. Randomized treatments were stopped after 6 weeks in the absence of specific indications, and the patients were followed up for 6 months. RESULTS: At 6 months, among patients randomized to lisinopril, 18.1% died or developed severe ventricular dysfunction versus 19.3% of those randomized to no lisinopril (2p = 0.03). No difference was found between patients with and without glyceryl trinitrate therapy (18.4% vs. 18.9%, 2p = 0.39). CONCLUSIONS: Although the systematic administration of glyceryl trinitrate started early and continued for 6 weeks after acute myocardial infarction does not yield evidence of benefit, early treatment with lisinopril appears to improve prognosis. This effect seems to carry over the first 6 months from randomization, even after treatment withdrawal.