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


Therapeutics

Aspirin reduced the risk for myocardial infarction and death in men with unstable coronary artery disease

ACP J Club. 1991 Jan-Feb;114:7. doi:10.7326/ACPJC-1991-114-1-007


Source Citation

The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet. 1990;336:827-30.


Abstract

Objective

To find whether low-dose oral aspirin or intravenous heparin, or a combination, decreases myocardial infarction and death in men with unstable coronary artery disease, non-Q-wave myocardial infarction, or unstable angina.

Design

Randomized, double-blind, 2 × 2 factorial, placebo-controlled trial. Patients were followed for a minimum of 3 months.

Setting

Coronary care units in 8 hospitals in southeast Sweden from May 1985 to June 1988.

Patients

Of 3365 men under 70 years of age who had non-Q-wave myocardial infarction or increasing angina within the previous 4 weeks, 945 met initial eligibility criteria. After randomization, 149 more were excluded, most for lack of evidence of myocardial ischemia on exercise testing, leaving 796 patients in the study.

Intervention

Patients were randomized to oral aspirin, 75 mg daily, plus intravenous heparin; aspirin and intravenous saline; placebo and heparin; placebo and saline. Bolus injections of 2 mL heparin, 5000 IU/mL, or saline, were given every 6 hours for 24 hours, followed by 1.5 mL every 6 hours for 4 days. Thereafter patients took aspirin or placebo only. Oral metoprolol (100 to 200 mg/d) was given unless contraindicated.

Main outcome measures

Death or nonfatal myocardial infarction, defined as 2 of the following: severe, enduring chest pain, diagnostic ECG, or elevated cardiac enzymes.

Main results

Patients started treatment a median of 33 hours after admission. The combination of aspirin and heparin (3 of 210 patients) showed a reduction in death or myocardial infarction in the first 5 days of treatment compared with double placebo (12 of 199) {1% vs 6%}*(P = 0.027). {This absolute risk reduction (ARR) of 5% means that 22 patients would need to be treated (NNT) with aspirin and heparin (compared with double placebo) to prevent 1 additional death or myocardial infarction, 95% CI 11 to 93; the relative risk reduction (RRR) was 76%, CI 23% to 93%.}* At 1 month, the risk for death or myocardial infarction for both groups on aspirin (17 of 399) was reduced compared with those on placebo (53 of 397) {4% vs 13%, (P < 0.001); ARR 9%; NNT 11, CI 8 to 19; RRR 68%, CI 46% to 81%}*. At 3 months, the risk was once again reduced for those taking aspirin (26 of 399) compared with placebo (68 of 397) {7% vs 17%, (P < 0.001); ARR 10%; NNT 9, CI 7 to 16; RRR 62%, CI 42% to 75%}*. The 16 deaths that occurred during the study were not significantly associated with the treatment group. Gastrointestinal symptoms occurred more frequently with aspirin than placebo (at 3 months, 5.2% to 6.5% for the aspirin groups compared with 0.7% to 1.9% for the placebo groups).

Conclusions

Aspirin, 75 mg daily for 3 months, in men with unstable coronary artery disease reduced the risk for myocardial infarction and death. Heparin in combination with aspirin reduced events during the first 5 days.

Sources of funding: Swedish National Association against Heart and Chest Diseases; Health Authority of Östergötland County; Hässle AB.

Address for article reprint: Dr. L. Wallentin, Division of Cardiology, University Hospital, S-581 85 Linköping, Sweden.

*Numbers calculated from data in article.


Commentary

A significant 5-day event reduction occurred for aspirin plus heparin compared with both double-placebo and placebo plus heparin, but not compared with aspirin plus placebo. A Canadian trial, however, found short-term benefits with heparin to be equivalent to heparin plus aspirin and superior to aspirin alone (1). The lack of an independent heparin effect in this study could be due to late initiation of treatment (81% started more than 24 hours after admission) or the modest bolus dosing schedule.

The study does confirm that low doses of aspirin are effective for up to 3 months. The authors suggest that the 75-mg dose is associated with similar benefits and fewer side effects than are found with higher doses in other studies (1-3). However, such interstudy comparisons may be misleading. Also, this study showed limited benefits in the first 48 hours of treatment, and the authors acknowledge that higher aspirin "loading" doses might have a faster antiplatelet action.

The ideal aspirin-heparin regimen for unstable angina remains unknown, and more trials are warranted. At present, higher doses of aspirin early (for example, 325 mg chewed at outset) and full intravenous heparinization for at least 5 days appear prudent.

C. David Naylor, MD, DPhil
Sunnybrook Health Science CentreToronto, Ontario, Canada


References

1. Theroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105-11.

2. Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone or both for unstable angina. N Engl J Med. 1985;313:1369-75.

3. Lewis HD, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med. 1983;309:396-403.