Six-month effects of early treatment with lisinopril and transdermal glyceryl trinitrate singly and together withdrawn six weeks after acute myocardial infarction: the GISSI-3 trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.
OBJECTIVE
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.
D000279:Administration, Cutaneous; D000328:Adult; D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017706:Lisinopril / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000453:epidemiology; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000627:therapeutic use; D011379:Prognosis; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D017706:Lisinopril; D005996:Nitroglycerin