• Adeel Shahzad, Vikram Khanna, Ian Kemp, Matthew Shaw, Christine Mars, Robert Cooper, Keith Wilson, Nick Curzen, and Rod H Stables.
• Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, United Kingdom.
• EuroIntervention. 2018 Mar 20; 13 (16): 1931-1938.

AimsThe HEAT-PPCI trial compared bivalirudin and unfractionated heparin in patients undergoing primary percutaneous coronary intervention (PPCI). The aim of this study was to report pre-specified, secondary analyses comparing the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events.Methods And ResultsAll patients received preprocedural oral antiplatelet therapy. During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For cases performed during working hours, multiple electrode aggregometry (MEA) was used to assess ADP-induced platelet aggregation at the end of the index procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all patients. Multiple logistic regression was used to adjust for differences in baseline characteristics. With MEA data from 469 patients, prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40 U (23, 78) (median; interquartile range [IQR]) when compared against ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In the entire study population (N=1,803), prasugrel therapy was associated with significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123; 7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31. Patients treated with clopidogrel had more high-risk features and clopidogrel use was more common as an alternative to prasugrel. After adjustment, there were no significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53).ConclusionsIn HEAT-PPCI, patients who received prasugrel (rather than clopidogrel or ticagrelor) had significantly greater suppression of ADP-induced platelet aggregation at the end of the procedure. After adjustment for differences in baseline characteristics, there were no significant differences in ischaemic or bleeding outcomes among the antiplatelet therapies.

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