Selectively Intensifying P2Y12 Inhibition in Poor Responders to Clopidogrel Decreases Thrombotic Events Without Increasing Bleeding Risk Following Percutaneous Coronary Intervention: A Systematic Review

Abstract

Background: Response to clopidogrel following percutaneous coronary intervention (PCI) varies, with a third of patients continuing to have high on-treatment platelet reactivity (HPR) with clopidogrel, increasing the risk of thrombotic events. Newer P2Y12 inhibitors reduce thrombotic event rates, but at the cost of increased bleeding risk. Selectively intensifying P2Y12 inhibition in patients with HPR on clopidogrel may be a superior approach. Aim: To systematically review current evidence regarding selective intensification of P2Y12 inhibition in patients with HPR on clopidogrel, identified around the time of PCI. Methods: Medline, Embase and the Cochrane Library databases were searched for studies published between 2012 and 2016. Inclusion criteria were a primary outcome of thromotic events and three patient groups: no-HPR, HPR on intensified therapy (HPRint) and HPR on standard therapy (HPRstd). Studies with multiple dose adjustments within the first month of therapy were excluded. Results: This review included four studies, encompassing 1080 patients with no-HPR, 289 with HPRint and 263 with HRPstd. Primary outcomes were composites of thombotic events, with follow-up periods between six months and two years. No differences in the primary event rates between no-HPR and HPRint patients were found. HPRstd event rates were 1.9 to 7.3-fold higher than the respective no-HPR group. Major bleeding did not significantly differ between treatment groups in all studies. Conclusion: Selective intensification of P2Y12 inhibition in patients with HPR on clopidogrel, identified around the time of PCI, dosing mitigates the increased risk of thrombotic events without increasing major bleeding risk.