ABSTRACT
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.
ABSTRACT
BACKGROUND: The A1166C polymorphism of the angiotensin II type 1 receptor (AT1R) gene, which appears to be the main receptor mediating the pleitropic vascular effects of angiotensin II in human beings, has been associated with the risk of myocardial infarction (MI), the severity of coronary vasoconstriction and the occurrence of sudden death. The question therefore arises whether the A1166C polymorphism constitutes a hereditary risk factor of survival after an acute myocardial infarction. METHODS AND RESULTS: In a large prospective study of 970 consecutive patients with a recent myocardial infarction the A1166C polymorphism was detected using a PCR based protocol. During the follow-up period (median, 2.5 years), 75 patients died and 62 from cardiovascular causes. The prespecified primary and secondary end points considered were total mortality and cardiovascular mortality. No differences between AA, AC, and CC groups were observed with respect to baseline clinical characteristics. Beyond conventional risk factors like age (RR=2.8 [1.6-5.0] 95% CI; p<0.001), hypercholesterolemia (RR=2.1 [1.2-3.7] 95% CI; p<0.014) or low left ventricular ejection fraction (RR=2.7 [1.5-4.8] 95% CI; p<0.002), the AT1R CC genotype was also identified as a strong independent predictor of death after myocardial infarction (RR=3.2 [1.5-7.0] 95% CI ; p<0.004). After adjustment for mortality causes, the AT1R CC genotype was confirmed to be an independent predictor of cardiovascular death after myocardial infarction (RR=2.8 [1.2-6.5] 95% CI; p<0.021). CONCLUSIONS: The AT1R CC genotype after adjustment is a strong predictor of death in post MI patients. This new finding may help to identify high risk post MI patients who may benefit from new therapeutic strategies.
