Early clinical outcomes as a function of use of newer oral P2Y12 inhibitors versus clopidogrel in the EUROMAX trial

Abstract

Objective: To ascertain whether different oral P2Y12 inhibitors might affect rates of acute stent thrombosis and 30-day outcomes after primary percutaneous coronary intervention (pPCI).

Methods: The European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) randomised trial compared prehospital bivalirudin with heparin with optional glycoprotein IIb/IIIa inhibitor treatment in patients with ST-segment elevation myocardial infarction triaged to pPCI. Choice of P2Y12 inhibitor was at the investigator's discretion. In a prespecified analysis, we compared event rates with clopidogrel and newer oral P2Y12 inhibitors (prasugrel, ticagrelor). Rates of the primary outcome (acute stent thrombosis) were examined as a function of the P2Y12 inhibitor used for loading and 30-day outcomes (including major adverse cardiac events) as a function of the P2Y12 inhibitor used for maintenance therapy. Logistic regression was used to adjust for differences in baseline characteristics.

Results: Prasugrel or ticagrelor was given as the loading P2Y12 inhibitor in 49% of 2198 patients and as a maintenance therapy in 59%. No differences were observed in rates of acute stent thrombosis for clopidogrel versus newer P2Y12 inhibitors (adjusted OR 0.50, 95% CI 0.13 to 1.85). After adjustment, no difference was observed in 30-day outcomes according to maintenance therapy except for protocol major (p=0.029) or minor (p=0.025) bleeding and Thrombolysis In Myocardial Infarction minor bleeding (p=0.002), which were less frequent in patients on clopidogrel. Consistent results were observed in the bivalirudin and heparin arms.

Conclusions: The choice of prasugrel or ticagrelor over clopidogrel was not associated with differences in acute stent thrombosis or 30-day ischaemic outcomes after pPCI.

Trial registration number: NCT01087723.

Keywords: bivalirudin; clopidogrel; prasugrel; stent thrombosis; ticagrelor.

Conflict of interest statement

Competing interests: KH has received personal fees from Daiichi Sankyo, Eli Lilly and The Medicines Company and personal fees and grants from AstraZeneca. GD has received personal fees from AstraZeneca, Biotronik, Bristol-Myers Squibb, Daiichi Sankyo and Eli Lilly. CWH has received personal fees from AstraZeneca, Eli Lilly and Sanofi-Aventis. AH has received grants from Daiichi Sankyo, Iroko and Medtronic. FL has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Correvio, Eli Lilly, Merck-Serono and The Medicines Company. PCo has received personal fees from The Medicines Company and grants from Daiichi Sankyo. GG has no disclosure to report. JS has received personal fees and grants from The Medicines Company. FWAV has received personal fees from AstraZeneca, Boehringer Ingelheim and Eli Lilly. JA has no disclosures to report. LN has received personal fees from Boehringer Ingelheim Pharma GmbH&Co. KG and The Medicines Company. VK has received personal fees from AstraZeneca and Boston Scientific. PCl has received personal fees from Bayer, Boehringer Ingelheim and Bristol-Myers Squibb and personal fees and grants from AstraZeneca, Daiichi Sanko, Eli Lilly, Medtronic, Pfizer, Sanofi and The Medicines Company. UZ has received personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, Pfizer and Sanofi. DB has received personal fees from The Medicines Company. JP has received personal fees from The Medicines Company. END was an employee of The Medicines Company at the time of the analysis and remains a shareholder. PGS has received personal fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Regeneron and Roche, personal fees and grants from Sanofi and Servier, and personal fees and non-financial support from The Medicines Company.

Figures

Figure 1

Flow chart. The numerical differences between loading and maintenance dose totals are due to missing data.

Figure 2

Adjusted* ORs for outcomes by maintenance P2Y12 treatment. *Adjusted for age>65 years, anaemia, bivalirudin versus heparin±glycoprotein IIb/IIIa inhibitor, new P2Y12 maintenance dose, creatinine clearance ≤60 vs >60 mL/min, current smoker, diabetes, drug-eluting stent, female sex, femoral versus radial access, hyperlipidaemia, hypertension, Killip class≥II, preprocedural TIMI flow 0/1 vs 2/3, history of coronary artery bypass graft, previous percutaneous coronary intervention, previous MI, single-vessel disease. MACE, major adverse cardiac events (death or myocardial infarction, ischaemia-driven revascularisation or stroke); MI, myocardial infarction; NACE, net adverse clinical events (death or myocardial infarction, ischaemia-driven revascularisation, stroke or bleeding); TIMI, Thrombolysis In Myocardial Infarction.