Key result
Potent P2Y12 inhibitors plus GPI show similar major bleeding risk to standard clopidogrel regimens.
Why the study?
The risk and benefit of GP-IIb/IIIa inhibition combined with recent highly active oral P2Y12 inhibitors in ACS remain unassessed.
Does the combination of GP-IIb/IIIa inhibitors and recent highly active oral P2Y12 inhibitors increase the risk of major bleeding compared to GP-IIb/IIIa inhibitors and standard clopidogrel in patients with acute coronary syndromes?
Meta-Analysis
Does the combination of GP-IIb/IIIa inhibitors and recent highly active oral P2Y12 inhibitors increase the risk of major bleeding compared to GP-IIb/IIIa inhibitors and standard clopidogrel in patients with acute coronary syndromes?
Relative Risk: 0.92 (95% CI 0.74–1.13)
The addition of GP-IIb/IIIa inhibitors to newer P2Y12 inhibitors (prasugrel or ticagrelor) does not disproportionately increase bleeding risk compared to standard clopidogrel, while preserving ischemic benefits in ACS patients.
Supports GP-IIb/IIIa use with potent P2Y12 inhibitors in ACS; confirms comparable bleeding safety to clopidogrel combinations.
The risk and benefit of GP-IIb/IIIa Inhibition (GPI) in combination with recent antiplatelet regimens in acute coronary syndromes (ACS) remain unassessed. The advent of fast-acting highly active oral P2Y12 inhibitors questions the additional value and risk of their association with GPI. We studied the effect of GPI in combination with prasugrel and ticagrelor, compared to clopidogrel on major bleeding in pivotal randomized controlled trials in the setting of ACS, using a meta-analytic approach. A similar analysis, further including the comparison of a double versus standard dose clopidogrel regimen, was performed for the risk of the primary efficacy endpoint. The combination of GPI and recent P2Y12 inhibitors was associated with a similar risk of bleeding as compared with GPI and the standard clopidogrel regimen (RR 0.92 [0.74; 1.13]). The benefit of recent regimens, including double dose clopidogrel, in reducing the primary ischemic endpoint (RR 0.86 [0.78; 0.94]) persisted in those treated with GPI. Although GPI use was associated with a consistent increase in the risk of bleeding in both recent (RR 1.27 [1.05–1.55]) and standard regimens (RR 2.01 [1.64–2.47]), the relative magnitude of such an increase was lower in association with prasugrel or ticagrelor as compared with clopidogrel. The risk of bleeding using a combination of GPI and oral antiplatelet regimens is mainly related to the use of GPI and not the oral antiplatelet regimen. Considering the absence of increased risk of bleeding and the persistence of the benefit of recent P2Y12 regimens in combination with GPI as compared with the standard clopidogrel regimen, the use of such a combination within the guidelines is supported by our findings.
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Roule et al. (2016) conducted a meta-analysis in Acute coronary syndromes (ACS). GP-IIb/IIIa inhibitors in combination with recent P2Y12 inhibitors (prasugrel and ticagrelor) vs. GP-IIb/IIIa inhibitors and standard clopidogrel regimen was evaluated on Major bleeding (RR 0.92, 95% CI 0.74-1.13). The combination of GP-IIb/IIIa inhibitors and recent P2Y12 inhibitors had a similar risk of major bleeding compared to GPI and standard clopidogrel in ACS patients (RR 0.92; 95% CI 0.74-1.13).
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