Cardiovascular Drugs and Therapy

, Volume 8, Issue 3, pp 469–472 | Cite as

The new trials: AIRE, ISIS-4, and GISSI-3. Is the dossier on ACE inhibitors and myocardial infarction now complete?

  • Lionel H. Opie
Post-Infarct Heart Failure: Section 3 Editorial


Recent studies have strengthened the arguments for the use of angiotensin-converting enzyme (ACE) inhibitors in the early postinfarct period. Those with clinically detectable heart failure, and hence at highest risk, will benefit most, as shown in the AIRE study, but those at lower risk with left ventricular dysfunction still have some benefit, theoretically through ventricular remodeling. In patients in the very early stages of acute myocardial infarction, three trials have shown discordant results. In CONSENSUS-II, intravenous enalaprilat followed by oral enalapril gave no benefit, rather causing excess hypotension and a possible increase in mortality. In ISIS-4 and GISSI-3, mortality improved by 0.46% and 0.8%, respectively, with risk reductions of 9% and 11%. Added transdermal nitrate in GISSI-3 gave a total reduction of 17%. In view of the risk of hypotension (20% in ISIS-4, compared with placebo 10%), very early ACE inhibition will probably only be used for selected patients. Logically, one target group would be those seen 7–24 hours after the onset of symptoms, particularly 7–12 hours, at which time captopril alone gave a reduction of 14.5% in risk. These mortality differences compare favorably with those recently found when comparing tPA and streptokinase in the GUSTO study.

Key Words

ACE inhibitors ramipril captopril lisinopril AIRE ISIS-4 GISSI-3 thrombolytic therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    ISIS-IV study (1994) (Fourth International Study of Infarct Survival). Ferguson JJ. Meeting highlights.Circulation 1994;89:545–547.Google Scholar
  2. 2.
    Swedberg K, Held P, Kjekshus J, Rasmussen K, et al. on behalf of the CONSENSUS II Study Group. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II).N Engl J Med 1992;327:678–684.PubMedGoogle Scholar
  3. 3.
    GISSI-3 (Gruppo Italiano per lo Studio della Sopravvivenza Nell' Infarto Mioeardico). Ferguson JJ. Meeting highlights.Circulation 1994;89:545–547.Google Scholar
  4. 4.
    MacFadyen RJ, Lees KR, Reid JL. Differences in first dose response to ACE inhibition in congestive cardiac failure—a placebo controlled study.Br Heart J 1991;66:206–211.PubMedGoogle Scholar
  5. 5.
    Pipilis A, Flather M, Collins R, et al. Hemodynamic effects of captopril and isosorbide monoitrate started early in acute myocardial infarction: A randomized placebo-controlled study.J Am Coll Cardiol 1993;21:73–79.PubMedGoogle Scholar
  6. 6.
    Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement Trial.N Engl J Med 1992;327:669–677.PubMedGoogle Scholar
  7. 7.
    Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure.Lancet 1993;342:821–828.Google Scholar
  8. 8.
    Taylor S. Diuretics in post-infarction heart failure.Cardiovasc Drugs Ther 1993;7:885–889.PubMedGoogle Scholar
  9. 9.
    Stevenson R, Ranjadayalan K, Wilkinson P, Roberts R, Timmis AD. Short and long-term prognosis of acute myocardial infarction since introduction of thrombolysis.Br Med J 1993;307:349–353.Google Scholar
  10. 10.
    GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction.N Engl J Med 1993;329:673–682.Google Scholar
  11. 11.
    Gersh BJ, Anderson JL. Thrombolysis and myocardial salvage. Results of clinical trials and the animal paradigm—paradoxic or predictable?Circulation 1993;88:296–306.PubMedGoogle Scholar
  12. 12.
    Weaver WD, Cerqueira M, Hallstrom AP, et al. for the Myocardial Infarction Triage and Intervention Project. Pre-hospital-initiated vs. hospital-initiated thrombolytic therapy. The Myocardial Infarction Triage and Intervention Trial.JAMA 1993;270:1211–1216.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Lionel H. Opie
    • 1
  1. 1.Hypertension Clinic, Groote Schuur Hospital and Medical Research Council Ischaemic Heart Disease Research UnitUniversity of Cape Town Medical SchoolCape TownSouth Africa

Personalised recommendations