Key result
Differences in major bleeding rates among trials of P2Y12 inhibitors in ACS patients are minimized after standardization of bleeding definitions, with TIMI major bleeding ranging from 1.1% to 7.7%.
Why the study?
Does the variability in major bleeding definitions affect the reported safety profiles of oral P2Y12 inhibitors in patients with ACS?
Systematic Review (n=119,020)
Yes
Does the variability in major bleeding definitions affect the reported safety profiles of oral P2Y12 inhibitors in patients with ACS?
Standardizing bleeding definitions and reporting timeframes minimizes apparent differences in major bleeding rates across trials of P2Y12 inhibitors in ACS.
Standardized bleeding definitions needed for valid cross-trial safety comparisons in ACS; confirms definition variability distorts reported rates.
AIMS: Various definitions of major bleeding have been used to evaluate safety in randomized controlled trials of antiplatelet therapy. We compared the definitions and rates of major bleeding in phase III randomized controlled trials of oral P2Y(12) inhibitors in the management of patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Electronic searches identified six phase III randomized controlled oral P2Y(12) inhibitor trials published between 2001 and 2010 involving 119 020 patients with ACS. The trials compared clopidogrel standard-dose (300-mg loading dose, 75-mg daily thereafter) vs. placebo (CURE, CLARITY-TIMI 28, COMMIT), clopidogrel standard-dose vs. prasugrel (TRITON-TIMI 38) or ticagrelor (PLATO) and clopidogrel standard-dose vs. clopidogrel double-dose (600-mg loading dose, 150-mg daily for 6-days, 75-mg daily thereafter) (CURRENT-OASIS 7). Using the trial definition, major bleeding rates in patients treated with standard-dose clopidogrel ranged from 0.6% in COMMIT to 11.2% in PLATO. The contrast in bleeding rates of standard-dose clopidogrel among the trials was attenuated when using the thrombolysis in myocardial infarction (TIMI) definition for major bleeding (range 1.1-7.7%) and bleeding rates in all the trials were less than 2% when comparing 30 day rates of non-coronary artery bypass graft surgery-related TIMI major bleeding (range 0.3-1.9%). CONCLUSION: Differences in major bleeding rates between trials of P2Y(12) inhibitors in patients with ACS are minimized after standardization of bleeding definitions, timing of reporting of bleeding outcomes, and procedure rates. Interpretation of the risk of bleeding associated with different P2Y(12) inhibitors would be facilitated by a consistent approach to the definition and reporting of bleeding.
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Quinlan et al. (2011) conducted a systematic review in Acute coronary syndromes (ACS) (n=119,020). Oral P2Y12 inhibitors vs. Placebo or standard-dose clopidogrel was evaluated on Major bleeding. Differences in major bleeding rates among trials of P2Y12 inhibitors in ACS patients are minimized after standardization of bleeding definitions, with TIMI major bleeding ranging from 1.1% to 7.7%.
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