Guided P2Y12 inhibitor therapy after percutaneous coronary intervention

Abstract

Antiplatelet treatment regimens for patients after percutaneous coronary intervention (PCI) have undergone major changes and substantial improvements. Extensions or a shortening of treatment as well as the use of various scores have been assessed in numerous trials to maximise anti-ischaemic efficacy and minimise bleeding. 1 Collet JP Thiele H Barbato E et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2020; (published online Aug 29.)https://doi.org/10.1093/eurheartj/ehaa575 Crossref PubMed Scopus (122) Google Scholar , 2 Knuuti J Wijns W Saraste A et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020; 41: 407-477 Crossref PubMed Scopus (1634) Google Scholar The key limitation of these strategies is the inherent time delay in the implementation of any therapy adjustments. At the same time, several clinical trials have investigated tailored and guided antiplatelet treatment. 3 Sibbing D Aradi D Alexopoulos D et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv. 2019; 12: 1521-1537 Crossref PubMed Scopus (180) Google Scholar Unfortunately, the pioneering trials of tailored treatment did not meet their primary endpoints or show improvement in patients' outcomes. 4 Price MJ Berger PB Teirstein PS et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011; 305: 1097-1105 Crossref PubMed Scopus (1130) Google Scholar , 5 Trenk D Stone GW Gawaz M et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity in Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy with Prasugrel) Study. J Am Coll Cardiol. 2012; 59: 2159-2164 Crossref PubMed Scopus (521) Google Scholar Various explanations have been attributed to these disappointing results, including insufficient intensification of treatment in patients with low response to clopidogrel by limited use of potent P2Y12 inhibitors and preferential inclusion of low-risk patients. 3 Sibbing D Aradi D Alexopoulos D et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv. 2019; 12: 1521-1537 Crossref PubMed Scopus (180) Google Scholar To address these issues, a series of recent trials included patients at higher risk and investigated the use of platelet function testing (phenotyping) 6 Sibbing D Aradi D Jacobshagen C et al. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017; 390: 1747-1757 Summary Full Text Full Text PDF PubMed Scopus (295) Google Scholar or genetic testing (genotyping) 7 Claassens DMF Vos GJA Bergmeijer TO et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med. 2019; 381: 1621-1631 Crossref PubMed Scopus (212) Google Scholar , 8 Pereira NL Farkouh ME So D et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA. 2020; 324: 761-771 Crossref PubMed Scopus (93) Google Scholar as a strategy by including study groups with a clear distinction of testing versus no testing. Notably, these trials did not provide unequivocal results and were partly limited in sample size and sometimes underpowered to compare specific ischaemic and bleeding endpoints. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysisGuided selection of antiplatelet therapy improved both composite and individual efficacy outcomes with a favourable safety profile, driven by a reduction in minor bleeding, supporting the use of platelet function or genetic testing to optimise the choice of agent in patients undergoing PCI. Full-Text PDF