Online searches of MEDLINE, EMBASE, BIOSIS, and the Cochrane Library were performed to a pre-specified protocol
from 1960 to March 2012 for randomized controlled trials (RCTs) and from January 1990 to March 2012 for
observational studies. A total of 47 studies (16 RCTs and 31 observational studies) were included. Cumulative
follow-up was 61 563 patient-years for RCTs and 484 241 patient-years for observational studies. The overall
median incidence of major bleeding was 2.1 per 100 patient-years (range, 0.9–3.4 per 100 patient-years) for
RCTs and 2.0 per 100 patient-years (range, 0.2–7.6 per 100 patient-years) for observational studies. With study
year as a proxy for changing management patterns, some evidence of bleeding rates and/or their reporting increasing
over time was noted. Mortality rates from observational studies were inadequately reported to allow comparisonwith those from RCT data