Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Ramipril reduced long-term mortality after MI

ACP J Club. 1997 Nov-Dec;127:57. doi:10.7326/ACPJC-1997-127-3-057


Source Citation

Hall AS, Murray GD, Ball SG, on behalf of the AIREX Study Investigators. Follow-up study of patients randomly allocated to ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Lancet. 1997 May 24;349:1493-7.


Abstract

Objective

To determine the long-term survival benefit of ramipril for congestive heart failure (CHF) after myocardial infarction (MI).

Design

Randomized, double-blind, placebo-controlled trial with 3-year follow-up after the end of the study.

Setting

30 clinical centers in the United Kingdom.

Patients

603 patients (mean age 65 y, 75% men) with confirmed MI complicated by CHF defined as left ventricular failure on erect posteroanterior chest radiograph, auscultatory evidence of pulmonary edema, or a third heart sound plus persistent tachycardia. Exclusion criteria were clinical instability, contraindications to angiotensin-converting enzyme (ACE) inhibitors, heart failure of primary valvular or congenital origin, or overt CHF that required ACE inhibitors. Follow-up was > 99% and 100% for death.

Intervention

Treatment was started 2 to 9 days after MI. 302 patients were allocated to ramipril, 1.25 to 2.5 mg twice daily titrated up to 2.5 to 5.0 mg twice daily, and 301 patients were allocated to placebo. Overt CHF was treated with open-label ACE inhibitors. At the end of the 15-month study, patients stopped their double-blind assigned medication and were treated at the discretion of their physicians.

Main outcome measure

Total mortality 3 years after the end of the trial.

Main results

At discharge from the hospital, 13.7% of patients allocated to ramipril and 5.3% of patients allocated to placebo were not taking their assigned medication. 3 years after the end of the study (minimum follow-up of 42 mo, mean 59 mo), 83 deaths (28%) had occurred in the ramipril group and 117 deaths (39%) had occurred in the placebo group (P = 0.002) (Table).

Conclusion

Ramipril reduced long-term mortality in patients with congestive heart failure after myocardial infarction.

Source of funding: Hoechst Marion Roussel.

For article reprint: Dr. A.S. Hall, Institute for Cardiovascular Research, The Yorkshire Heart Centre, University of Leeds, Leeds LS2 9JT, England, UK. FAX 44-113-233-4803.


Table. Ramipril vs placebo for congestive heart failure*

Outcome at mean 59 mo Ramipril EER Placebo CER RRR (95% CI) ARR |EER-CER| NNT (CI)
Death 28% 39% 36% (15 to 52) 11% 9 (5 to 26)

*Abbreviations defined in Glossary; CI for NNT calculated from data in article.


Commentary

β-blocker therapy is standard after MI. The original studies showed a short-term mortality benefit (1). It was not until the 7-year follow-up of the Norwegian timolol study (2) that this benefit was shown to be maintained over time. The same kind of information is now available on the use of ACE inhibitors in the treatment of patients with CHF after MI.

The Survival and Ventricular (SAVE) (3) and International Study of Infarct Survival (ISIS-4) (4) trials showed that the judicious use of these drugs several days after MI decreased the short-term mortality rate. Such studies as the Studies of Left Ventricular Dysfunction (SOLVD) trial (5), which showed the benefit of these drugs in CHF without acute MI, did not reveal a link between the timing of the start of therapy to the onset of congestive symptoms. Combining these 2 ideas would suggest to the clinician that patients with acute MI who developed CHF would benefit from long-term treatment.

The study by Hall and colleagues directly addresses this issue by showing an ongoing mortality benefit at 42 months when the ACE inhibitors were begun 2 to 9 days after MI. The 11% absolute risk reduction in mortality is even more remarkable because any patient who developed CHF during follow-up was permitted to receive an open-label ACE inhibitor. The drug was blindly compared with placebo only during the first 15 months of the study. It is also important to note that the magnitude of the survival benefit did not increase after 24 months, again perhaps because the use of ACE inhibitors was not restricted.

It took several years for ACE inhibitors to be widely used for CHF. Now we have excellent data showing that these agents are highly beneficial in reducing mortality in patients with CHF after MI in both the short and long term.

Robert S. Weiss, MD
Androscoggin Cardiology Association Auburn, Maine, USA


References

1. JAMA. 1982;247:1707-14

2. Pedersen TR. N Engl J Med. 1985;313: 1055-8.

3. Pfeffer MA, Braunwald E, Moye LA, et al. N Engl J Med. 1992;327:669-77.

4. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet. 1995;345:669-85.

5. The SOLVD Investigators. N Engl J Med. 1991;325:293-302.