Five RCTs (n=18,626) were included.
One study scored 4 points for study quality, three scored 3 points and one scored 2 points. Two studies were double-blind; the others were open-label trials.
No RCTs were found that statistically compared oral anticoagulation versus oral anticoagulation plus aspirin for long-term secondary prophylaxis. No studies were identified that assessed oral anticoagulants at the currently recommended International Normalised Ratio (INR) range of 2.0 to 3.5.
Oral anticoagulation versus aspirin (3 RCTs).
Efficacy: one study found that oral anticoagulation significantly reduced the risk of MI compared with aspirin (7.4% versus 9.7%, P<0.001); the other two studies found no significant difference between treatments. One study (a different study from the single positive study above) found that oral anticoagulation significantly reduced all-cause mortality compared with aspirin (1.2% versus 4.5%, P<0.05); the other two studies found no significant difference between treatments.
Safety: two studies found no significant difference in major bleeding between treatments; the other study did not report the statistical significance of the difference. One study found that oral anticoagulation significantly increased minor bleeding compared with aspirin (8.9% versus 1.5%, P=0.02); one study did not report the statistical significance of the difference and the other found no significant difference between treatments.
Oral anticoagulation plus aspirin versus aspirin alone (5 RCTs).
Efficacy: one study found that oral anticoagulation plus aspirin significantly reduced MI compared with aspirin alone (5.7% versus 9.7%, P=0.03); the other four studies found no significant difference between treatments. None of the studies found any significant difference in all-cause mortality between treatments.
Safety: one study found that oral anticoagulation plus aspirin significantly increased major bleeding compared with aspirin alone (3.5% versus 2.0, P<0.001); one study did not report the statistical significance of the difference and the others found no significant difference between treatments. Three studies found that oral anticoagulation significantly increased minor bleeding compared with aspirin alone (15.1% versus 4.8%, P<0.05; 9.8% versus 1.5%, P<0.05; and 13.8% versus 3.0%, P<0.001 respectively); one study found that combination treatment increased minor bleeding but the statistical significance was not reported; the other study did not report minor bleeding.
Oral anticoagulation versus oral anticoagulation plus aspirin (3 studies).
None of the studies statistically compared efficacy or safety outcomes between treatments.
Efficacy: the review reported that event rates for mortality and MI were similar between treatments, but no data were presented.
Safety: the studies reported mixed results for major bleeding: two found increased major bleeding with oral anticoagulation alone and the other found increased major bleeding with combination treatment. All three studies found that oral anticoagulation plus aspirin increased minor bleeding compared with oral anticoagulation alone, but the statistical significance was not reported.