Twenty-six RCTs from 1960 to 1994 (73,000 patients) were identified. Low-dose heparin in the absence of other antithrombotics: 7 trials from 1972 to 1989 (807 patients). High-dose heparin without other antithrombotics: 8 trials from 1960 to 1990 (1,678 patients). High-dose heparin plus oral anticoagulants without other antithrombotics: 6 trials from 1972 to 1987 (2,592 patients). High-dose heparin in presence of aspirin: 6 trials from 1987 to 1994 (68,090 patients).
Heparin in the absence of aspirin: a 25% (95% confidence interval, CI: 10, 38, 2P=0.002) proportionate reduction in mortality in patients allocated to heparin treatment was found. There was a non significant difference in reinfarction rates between treatment groups.
Proportionate reduction in stroke in the heparin treatment group: 49% (approximate 95% CI: 33, 67, 2P=0.01).
Reduction in pulmonary embolism in the heparin group: 51% (approximate 95% CI: 33, 67, 2P<0.001).
The analysis was repeated after excluding trials where knowledge of the treatment group may have influenced assessment of pulmonary embolism; a similar reduction was observed.
The reporting of bleeding was stated to be incomplete: in trials of high-dose heparin there was a doubling of the risk of a major noncerebral bleed (31 out of 1,322 versus 14 out of 1,321 patients; 2P=0.01).
None of the above showed statistically-significant heterogeneity between heparin regimes.
Heparin in the presence of aspirin: a 6% proportionate reduction in death was found in the heparin group (95% CI: 0, 10, 2P=0.03). The reduction was smaller than that seen in the absence of aspirin (chi-squared=5.82, P<0.05).
Adding heparin to aspirin produced no additional reduction in strokes compared to aspirin alone.
There was a 50% increase in the odds of having a major bleed reported in the heparin plus aspirin group, compared to the aspirin group (1 versus 7%; 2P<0.001).