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The safety of glycoprotein (GP) IIb/IIIa inhibitors has been well documented in clinical trials. Although these trials have included a broad patient population, the strict enrollment criteria may have resulted in exclusion of patients at a higher risk of bleeding complications. The authors conducted a retrospective chart review of 1020 consecutive patients who received GP IIb/IIIa inhibitors and underwent percutaneous coronary intervention in a large community hospital. They used Thrombolysis in Myocardial Infarction (TIMI) criteria to define major or minor bleeding complications. Bleeding complications developed in 214 (21%)patients, with major bleeding in 89 (9%). Univariate predictors of bleeding were older age, lower body weight, elevated serum creatinine, higher activated partial thromboplastin time (aPTT) level, history of diabetes mellitus (DM), peripheral vascular disease (PVD), congestive heart failure (CHF), and emergency procedure for acute myocardial infarction (AMI). Multivariate predictors of major bleeding were PVD (20% in bleeding group vs 11% in nonbleeders, odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.2–2.6, P < .004), age (68 ± 2 years, 95% CI = 66–70 in bleeding group vs 63 ± 13 years, 95% CI = 61.2–63 in nonbleeders, P < .001), and higher aPTT level (66 ± 27 seconds, 95% CI= 63–70 in bleeding group vs 53 ± 28 seconds, 95% CI= 51–56 in nonbleeders, P < .001). The risk of bleeding in the large community hospital setting may be higher than in randomized clinical trials. This increased risk is associated with higher hospitalization costs. Recognition of predictors of bleeding should further enhance the safety of these antiplatelet agents.