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Expert review

Prognostic impact of major bleeding in patients with acute coronary syndromes. A systematic review and meta-analysis

Aims: The causative relationship between major bleeding in acute coronary syndromes (ACS) and the increase in mortality and morbidity has frequently been suggested in recent pharmaco-invasive trials and registries. However, the magnitude of this increased risk is the subject of debate. In order to determine the prognostic significance of major bleeding in ACS, we have conducted a systematic review and meta-analysis.

Methods and results: Databases were searched for articles published up to March 2007. Any study, either retrospective or prospective, assessing the impact of major bleeding in patients with ACS was included if all-cause mortality was reported as an outcome measure.

Data from 10 studies involving a total of 133,597 patients with ACS at baseline, of whom 3,644 had major bleeding (2.7%) were included in a meta-analysis using a random-effects model. An overall pooled relative risk (RR) mortality increase of 7.6 (95% CI; 5.5-10.4) was found in patients with major bleeding. Although most of the 95% confidence intervals (CIs) for the primary studies overlapped, some heterogeneity was observed (Chi2 for heterogeneity, P <0.0001), hence the need for the random-effects meta-analysis. However, the overall effect was highly significant (Z=12.65; P <0.00001). Major bleeding in ACS was also associated with a statistically significant increase in the secondary endpoints assessed including acute myocardial infarction (AMI), and stroke.

Conclusions: This meta-analysis indicates that major bleeding in patients with ACS is a strong predictor of in-hospital or 30-day death and AMI. The pooled estimates presented should alert clinicians and interventionalists to the importance of prevention of major bleeding in patients hospitalised with ACS.

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