Low-dose aspirin prevents cardiac events in silent myocardial ischemia
ACP J Club. 1993 Jan-Feb;118:6. doi:10.7326/ACPJC-1993-118-1-006
Nyman I, Larsson H, Wallentin L, and the Research Group on Instability in Coronary Artery Disease in Southeast Sweden. Prevention of serious cardiac events by low-dose aspirin in patients with silent myocardial ischaemia. Lancet. 1992 Aug 29;340:497-501.
To study the effect of low-dose aspirin on mortality and subsequent myocardial events in men with silent and symptomatic myocardial ischemia.
Subgroup analysis of a randomized, double-blind, controlled trial with 3-month follow-up (RISC Study).
8 research, central, and district hospitals in Sweden.
All men < 70 years of age who were hospitalized for unstable coronary artery disease (non-Q-wave myocardial infarction, new or increasing chest pain within the previous 4 weeks). Exclusion criteria were acute myocardial infarction; presence of QS complexes in ≥ 2 adjacent leads; myocardial dysfunction requiring treatment; valvular heart disease; left bundle branch block; heart rate >150 beats/min; and treatment with aspirin, anticoagulants, pacemakers, or coronary bypass surgery. The mean age was 59.5 years. Of 740 men who had predischarge exercise testing, 230 had chest pain and ST depression (symptomatic ischemia), and 144 had asymptomatic ST depression (silent ischemia).
Patients received aspirin, 75 mg/d, or placebo and either 5 days of fixed-dose intravenous heparin or placebo. 77 men allocated to aspirin and 67 to placebo had silent ischemia. 105 men allocated to aspirin and 125 to placebo had symptomatic ischemia. Follow-up was 100%. The study was terminated early because of positive ISIS-2 results.
Main outcome measures
Mortality, myocardial infarction, and severe angina. Patients were examined at hospital discharge and 3 and 12 months later.
At 3 months, 4% of patients with silent ischemia taking aspirin and 21% taking placebo had died or had a myocardial infarction (P =0.005). At 12 months the rates were 9% and 28%, respectively (P = 0.005). For patients with symptomatic ischemia, the rates for death or myocardial infarction were 9% and 18% at 3 months (P = 0.05). At 12 months, they were 13% and 22% for aspirin and placebo groups, respectively (P = 0.1). Revascularization and severe angina did not differ.
Low-dose aspirin reduced mortality and myocardial infarction rates in men with silent and symptomatic ischemia.
Sources of funding: Swedish National Association against Heart and Chest Diseases; Health Authority of Östergötland County; Hässle AB.
For article reprint: Dr. L. Wallentin, Division of Cardiology, Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden. FAX 46-18-551-217.
The study by Nyman and colleagues reinforces the original RISC report (1) in 2 areas. First, this study showed that low-dose aspirin is effective in lowering mortality in the population studied. Second, it showed an effect not limited to those with provocable and symptomatic ischemia. Aspirin was as effective in silent ischemia as it was in symptomatic ischemia.
The study claims to be among the first to show a favorable effect on outcome when patients with silent ischemia are treated medically. The definition of silent ischemia was based, however, on a predischarge exercise test showing symptomless ST depression during hospitalization for non-Q-wave or unstable angina. These patients may not be identical to stable patients defined as having silent ischemia by Holter monitor during daily activity. Second, the design was a subgroup analysis. Although baseline characteristics of the silent and symptomatic groups were comparable, symptomatic state was not the basis for randomization. The conclusion—that aspirin lowers mortality in patients with silent ischemia after myocardial infarction or unstable angina—should conservatively be termed "hypothesis generating" rather than conclusive. The comprehensive overview by the Antiplatelet Trialists' Collaboration supports the findings of this study and shows substantial reductions in mortality and cardiovascular events in a wide range of high-risk patients treated with aspirin including patients with any type of vascular disease (2).
The study population included patients who are at high risk for cardiovascular events and death and in whom compelling evidence already favors aspirin treatment. Thus, the study offers little beyond the original report in terms of practice recommendations (1).
Steven Borzak, MD
Henry Ford HospitalDetroit, Michigan, USA
2. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatet therapy—1: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ. 1994;308:81-106.