The effects of oral isosorbide 5-mononitrate on mortality following acute myocardial infarction: A multicentre study*

Abstract

We have conducted a randomized, double-blind, placebo-controlled multicentre trial of oral isosorbide 5-mononitrate (ISMN) in 360 patients with suspected acute myocardial infarction. Patients were stratified prior to analysis according to the presence or absence of left ventricular failure on admission. ISMN caused a significant reduction in systolic and diastolic blood pressure during the first 12 h. There was no significant effect on heart rate. Overall mortality was 4.9% in the ISMN group compared with 4.0% in controls at 5 days, and 14.1% compared with 10.5% at 6 months (NS). A non-significant reduction in mortality in the ISMN group with heart failure (ISMN 7.9%, placebo 12.9%, at 5 days) contrasted with a non-significant increase in mortality in patients without heart failure treated with ISMN (ISMN 4.1%, placebo 2.1%, at 5 days). Lignocaine was used in twice as many patients in the ISMN group as in placebo group (P less than 0.01), both with and without heart failure. Diamorphine usage was similar in the ISMN and control groups. Oral ISMN has similar haemodynamic effects to intravenous nitroglycerin, and can be of benefit in acute myocardial infarction with heart failure. However, our results question the use of nitrates in acute myocardial infarction in the absence of heart failure.

Long-Term Nitrate Therapy After Acute Myocardial Infarction Does not Improve or Aggravate Prognosis

“…2,18 Fitzgerald et al also reported that oral nitrates resulted in non-significant mortality reduction in patients with AMI followed up for 6 months. 19 These data suggest that nitrate treatment may be beneficial in patients with heart failure caused by moderate or large MI. On the other hand, Ishikawa et al 7 and Kanamasa et al 8 concluded from their prospective studies that long-term treatment with nitrates increased total mortality and cardiac events in patients after AMI during approximately 18-month follow-up period.…”

Effects of nitrates on mortality in acute myocardial infarction and in heart failure.

“…In addition five trials of oral nitrates have been published (Fitzgerald & Bennet, 1990;Mellen et al, 1967;Newell & clinical collaborators, 1970;Oscharoff, 1964;Ryan & Schnee, 1965 (Jugdutt & Warnica, 1988). The other trial followed 60 patients for 18 months and reported a 4/31 (13%) mortality in actively treated patients and 12/29 (41%) in control patients (P <0.02) (Bussmann etal., 1981 (Yusuf et al, 1988).…”

“…Nitrates were given for some days to weeks and in one trial for 6 months (range, 5 days to 6 months). Four trials used pentaerythritol tetranitrate (Mellen et al, 1967;Newell and clinical collaborators, 1970;Oscharoff, 1964;Ryan & Schnee, 1965) and one isosorbide-5-mononitrate (Fitzgerald & Bennet, 1990 Leier et al (1983) 30 III-IV improved** P <0.05 Odds ratio (95% Cl) 1967; Oscharoff, 1964;Ryan & Schnee, 1965), in one, the 21-day mortality was available (Newell and clinical collaborators, 1970) and in the fifth trial, 6 months' mortality was reported. One of the five trials reported a conventionally significant reduction in mortality in the actively treated patients (Oscharoff, 1964).…”

Eccentric Dosing of Nitrates Does Not Increase Cardiac Events in Patients with Healed Myocardial Infarction

“…The efficacy of short-term administration of nitrates for treating myocardial infarction during the acute phase has been well established (1)(2)(3). In 1999, the Committee on Management of Acute Myocardial Infarction reported that intravenous nitroglycerin was not useful for patients with systolic blood pressure (SBP) less than 90 mmHg or bradycardia less than 50 bpm (4).…”