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

To 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). Prospective, single-centre study wherein consecutive patients undergoing nonemergent PCI showing HTPR on 600 mg clopidogrel loading were randomized to either clopidogrel reloading (300 mg load, 75 mg OD) or prasugrel (60 mg load, 10 mg OD-in patients > 60 kg) or ticagrelor (180 mg load, 90 mg BD). HTPR is defined as maximum platelet aggregation (MPA) > 46% assessed by 5 μmol/L adenosine diphosphate light transmission aggregometry (ADP-LTA) assay after more than 6 h of clopidogrel loading. Platelet function were assessed at baseline, 6 h or more after clopidogrel loading, 2 h after reloading, day 1 and day 30 post-PCI. 107 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 2 h 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). In 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.