Research on Instability in Coronary Artery Disease - RISC


Aspirin and heparin for 3-month mortality in acute MI.


Oral aspirin (75 mg/day) for up to 1 year and intravenous heparin (5,000 IU/ml) during the initial 5 days of treatment would reduce the incidence of MI and mortality after an episode of unstable CAD.

Study Design

Study Design:

Patients Screened: 8,136
Patients Enrolled: 976
NYHA Class: Not given
Mean Follow Up: 3 months
Mean Patient Age: 58.2
Female: 0
Mean Ejection Fraction: Not given

Patient Populations:

Men < 70 years old admitted to coronary care unit
Diagnosis of unstable CAD: either non-Q wave myocardial infarction or increasing symptoms of anginal chest pain over 4 weeks with signs of ischemia at effort or rest.


Q-wave MI
Presence of QS-complexes in 2 or more adjacent chest leads
Myocardial dysfunction from previous MI or non-ischemic heart disease
Valvular heart disease
Previous coronary bypass surgery
Left bundle branch block
Pacemaker treatment
Heart rate above 150 at admission
Inability to complete an ET because of physical handicap
Severe non-cardiac disease
Concurrent anticoagulant or aspirin therapy
Increased risk of bleeding
Aspirin allergy
Anticipated poor compliance
Participation in this or another medical trial
Refusal to participate

Primary Endpoints:

3 months minimum treatment and follow-up. Study was planned to continue for > 1 year; however, publication of ISIS-2 results in August 1988, demonstrating efficacy of 165 mg of aspirin, caused an ad-hoc safety committee to recommend early termination of the study.

Secondary Endpoints:

MI (two of the following: severe chest pain of long duration, a diagnostic ECG, or an increase of cardiac enzymes above the upper reference level)
Non-Q-wave infarction (MI without development of significant Q-waves)
Treatment failure in hospital (recurring chest pain despite maximal antianginal medication for 1 week) requiring urgent angiography and revascularization
Treatment failure during follow-up (persisting angina--- NYHA Group 3-- despite maximum medical treatment for 1 month leading to coronary angiography and revascularization)
Death (with or without MI or non-Q-wave infarction)

Drug/Procedures Used:

Intermittent bolus injections of heparin 5000 IU/ml qid (2 ml) during first 24 h, followed by 1.5 ml qid for 4 days
Oral aspirin 75 mg qd for duration of study

Concomitant Medications:

Oral metoprolol 100-200 mg/day
Oral nitrates
Calcium antagonist

Principal Findings:

Oral aspirin (75 mg/day) reduced the risk of MI and death (57-69%).
Aspirin also reduced the occurrence of non-Q-wave MI and unstable angina. Major benefits were seen during the first three months of aspirin use.
Heparin alone had no significant influence on event rate.
Combined aspirin and heparin reduced the number of events during the first 5 days (75%) compared with either heparin alone or placebo.
Side effects of bleeding were rare and minor.
Patient compliance was high.


Treatment of vascular disease with low-dose oral aspirin reduces the risk of MI and death with a low frequency of side effects. A dose of 75 mg/day provides the required suppression of platelet aggregation. Because side-effects at this low dosage are few, patient compliance is high.


1. J Am Coll Cardiol 1991;18:1587-93. Design and baseline results
2. Lancet 1992;336:827-830. Long-term (1-year) follow-up

Clinical Topics: Anticoagulation Management

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Heparin, Coronary Disease, Patient Compliance

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