Pharmacodynamic evaluation of clopidogrel reloading vs. switching to prasugrel or ticagrelor in clopidogrel resistant Indian patients

AbstractObjectivesTo compare the pharmacodynamic effects of clopidogrel reloading vs. switching to prasugrel or ticagrelor in high on treatment platelet reactivity (HTPR) patients undergoing percutaneous coronary intervention (PCI).MethodsProspective, single-centre study wherein consecutive patients undergoing nonemergent PCI showing HTPR on 600mg clopidogrel loading were randomized to either clopidogrel reloading (300mg load, 75mg OD) or prasugrel (60mg load, 10mg OD-in patients>60kg) or ticagrelor (180mg load, 90mg BD). HTPR is defined as maximum platelet aggregation (MPA)>46% assessed by 5μmol/L adenosine diphosphate light transmission aggregometry (ADP-LTA) assay after more than 6h of clopidogrel loading. Platelet function were assessed at baseline, 6h or more after clopidogrel loading, 2h after reloading, day 1 and day 30 post-PCI.Results107 patients enrolled in the study, 32 (29.9%) were found to have HTPR. 10 (9.3%) patients were reloaded with clopidogrel, 10 (9.3%) with prasugrel and 12 (11.2%) with ticagrelor. Mean MPA in clopidogrel, prasugrel and ticagrelor reloaded patients was 42.6±12.5%, 15.8±8.6% and 14.6±7.2% respectively at 2h after reloading and was 43.7±13.5%, 15.4±5.6% and 12.6±4.6% on day 1 post-PCI. The MPA significantly reduced in prasugrel and ticagrelor cases and not in clopidogrel, also prasugrel and ticagrelor had almost similar MPA after the reload. There was no patient with continued HTPR with ticagrelor or prasugrel while 50% (5/10) of clopidogrel reloaded patients had HTPR. The pharmacodynamic efficacy of maintenance with prasugrel or ticagrelor was better than clopidogrel (MPA at day 30 post-PCI; 15±9.7%, 13.9±5.1% and 50.4±13.1% respectively).ConclusionIn patients undergoing PCI exhibiting HTPR after clopidogrel loading, ticagrelor or prasugrel reloading produced improved platelet inhibition which was better than clopidogrel reload and this effect was sustained during maintenance phase