Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61,898 patients from randomized trials

Literature - Galli M, Benenati S, Franchi F et al., - Eur Heart J 2021; doi.org/10.1093/eurheartj/ehab836

Introduction and methods

Background

Platelet function and genetic testing can be used as tools to guide P2Y12 inhibitor therapy to administer the more potent P2Y12 inhibitors ticagrelor and prasugrel to clopidogrel poor responders [1,2]. No consistent results on the effect of a guided selection of antiplatelet therapy were observed in RCTs, but a meta-analysis demonstrated that a guided selection of antiplatelet therapy was associated with improved outcomes compared to standard selection of antiplatelet therapy in patients undergoing PCI [3]. Data on the acute setting are lacking.

In this network meta-analysis the safety and efficacy of oral P2Y12 inhibitor strategies, including a guided selection approach by platelet function or genetic testing, was examined for the treatment used in the setting of ACS.

Study design

RCTs comparing oral P2Y12 inhibitors for the treatment of patients with ACS (clopidogrel, prasugrel, ticagrelor) were included. RCTs including a guided approach vs. standard selection of P2Y12 inhibitors in patients with ACS were also included. A systematic search was done in large databases using search terms.

15 RCTs with a total of 61,898 patients and mean follow-up of 11.9 months were included in the analysis.

Clopidogrel represented the reference treatment.

Primary outcomes

Primary efficacy outcome was MACE, as defined in each individual included trial. Primary safety endpoint was all bleeding.

Main results

Primary outcome

• There was a reduction in the primary efficacy endpoint of MACE with a guided approach compared with clopidogrel (RR 0.80, 95%CI:0.65-0.98), but not with prasugrel (RR 0.89, 95%CI:1.77-1.03) and ticagrelor (RR 1.00, 95%CI:0.86-1.18).
• All bleeding was increased with prasugrel (RR 1.36, 95%CI:1.14-1.63) and ticagrelor (RR 1.37, 95%CI:1.16-1.61) but not with a guided approach (RR 1.22, 95%CI:0.96-1.55) compared with clopidogrel.

Secondary outcomes

• A guided selection of P2Y12 inhibiting therapy, prasugrel and ticagrelor were associated with a reduction of stent thrombosis, while only a guided approach and prasugrel were associated with a reduction of MI.
• None of the treatments reduced the risk of stroke compared with clopidogrel.
• Prasugrel and ticagrelor, but not a guided selection of P2Y12 inhibiting therapy, were associated with increased risk of minor bleeding, while only prasugrel was associated with an increased risk of major bleeding compared with clopidogrel.
• Only ticagrelor was associated with an reduction of all-cause and CV mortality compared with clopidogrel.

Ranking of treatment strategies

• A guided selection of P2Y12 inhibiting therapy ranked as best treatment with regard to the outcomes of MACE, MI, stroke and all-cause death, and ranked second in terms of bleeding outcomes. Overall, it had the most favorable safety and efficacy profile.

Conclusion

References

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