Effect of medical thromboprophylaxis on mortality from pulmonary embolus and major bleeding

BACKGROUND: Several studies have failed to discover a beneficial effect of medical thromboprophylaxis on mortality. AIMS: To examine the relative influence of acute fatal pulmonary embolism (PE) and fatal major haemorrhage on overall mortality in medical patients treated with low molecular weight heparin (LMWP) for prophylaxis. METHODS: The author compared deaths from the above factors using data from a recent Cochrane Collaboration meta-analysis. Data from trials satisfying the criteria of the Cochrane analysis plus additional exclusions to avoid bias were pooled to produce point estimates of mortality from PE and major bleeds to estimate net mortality benefit. Estimates were then subject to limited sensitivity analysis based on reported epidemiological data. RESULTS: Reported PE and major bleeds were 0.44 per cent and 0.27 per cent, respectively. The corresponding case-specific mortality rates were 30.8 per cent and 12.8 per cent and the relative risk reduction (RRR) for PE was 23.2 per cent. Estimated deaths from major bleeds exceeded PE deaths avoided by a small margin (3/100,000 patients given prophylaxis). This excess increased to 30/100,000 when more plausible literature values for PE case fatality rates were applied. CONCLUSION: Medical thromboprophylaxis has a finely balanced effect on mortality but may increase it. Such an effect would explain the failure to discover a mortality benefit from medical thromboprophylaxis. Further work, including a formal meta-analysis and additional clinical studies, is required to confirm this picture.