A total of 30 reports of 31 trials (n=23397) were included in the analysis. Of these, 20 were classified as high intensity (INR <2.8) (n=11692), eight were classified as moderate intensity (INR 2-3) (n=3270), and three as low intensity (INR <2) (n=8435).
High intensity OA versus control: the ORed for mortality was 22% (95% CI: 13%, 31%, p<0.001) and that for MI was 42% (95% CI: 34%, 48%, p<0.001) and for thromboembolic events was 63% (95% CI: 53%, 71%, p<0.001). For stroke specifically the ORed was 48% (95% CI: 33%, 60%, p<0.001). There was a 6-fold ()&= 6.0,95% CI: 4.4, 8.2) increase in major bleed. The risk benefit in terms of number of events prevented: number of major bleeds caused per 1000 patients treated was 98 (95% CI: 73,123): 39 (95% CI: 35, 43).
Moderate intensity INR: The ORed OA versus control for mortality was 18% (95% CI: -6%, 37%, p> 0.1), and for MI was 52% (95% CI: 37%, 64%, p< 0.001) and for stroke was 53% (95% CI: 19%, 73%, p=0.02), with an associated 7.7-fold increase in risk of bleeding (OR =7.7,95% CI: 3.3, 17.6, p<0.001). The risk benefit in terms of number of events prevented: number of major bleeds caused per 1000 patients treated was 24 (95% CI: 22,26): 35 (95% CI: 21,49).
High or moderate intensity versus aspirin (three trials): No reduction in death, MI or stroke was observed compared with aspirin and treatment was associated with a 2.4-fold (OR =2.4, 95% CI: 1.6, 3.6) increase in major bleeding. The risk benefit in terms of number of events prevented: number of major bleeds caused per 1000 patients treated was 13 (95% CI: 11, 14): 14 (95% CI: 12, 16).
Combination of OA and aspirin compared with aspirin alone had an ORed of 56% (95% CI: 17%, 77%, p-0.01), and an associated increase in major bleeding of 1.9-fold (955 CI: 0.6, 6.0, NS), but this is based on three trials with a total of only 480 patients. The risk benefit in terms of number of events prevented: number of major bleeds caused per 1000 patients treated was 54 (95% CI: 43, 65): 16 (95% CI: 10-22).
Low intensity OA plus aspirin: no reduction in death, MI or stroke was observed compared with and treatment was associated with a 1.3-fold (95% CI: 1.0, 1.8) increase in major bleeding. The risk benefit in terms of number of events prevented: number of major bleeds caused per 1000 patients treated was 7 (95% CI: 6,8): 5 (95% CI: 4,6).