Pharmacodynamic evaluation of clopidogrel reloading vs. switching to prasugrel or ticagrelor in clopidogrel resistant Indian patients Sandeep Khasa, Roopali Khanna, Fauzia Ashfaq, Pravin K. Goel ⁎ Department of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, India abstract article info Article history: Received 23 June 2015 Received in revised form 26 October 2015 Accepted 28 October 2015 Available online 11 November 2015 Keywords: HTPR — high on treatment platelet reactivity PCI — percutaneous coronary intervention MPA — maximum platelet aggregation ADP-LTA — adenosine diphosphate light transmission aggregometry Objectives: 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 interven- tion (PCI). Methods: 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 N 60 kg) or ticagrelor (180 mg load, 90 mg BD). HTPR is defined as maximum platelet aggregation (MPA) N 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. Results: 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). Conclusion: 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. © 2015 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction Current guidelines recommend treating patients undergoing percutaneous coronary intervention (PCI) and drug-eluting stent implan- tation with a loading dose of P2Y12 receptor antagonist and continuation of same for at least 1 year [1]. Clopidogrel resistance has been defined as high on treatment platelet reactivity (HTPR) [2]. Variable antiplatelet responses to clopidogrel are primarily based on metabolic phenotype of cytochrome 2C19 (CYP2C19) genotype. Patients who are carriers of loss-of-function alleles in the hepatic CYP2C19 system have lower clopidogrel active metabolite levels and are thus clopidogrel resistant [3,4]. High on treatment platelet reactivity (HTPR) while on clopidogrel has been seen to be associated with high adverse event rates in patients undergoing percutaneous coronary intervention (PCI) [5–7]. Newer P2Y12 inhibitors, prasugrel and ticagrelor, are accompanied by a stron- ger and more consistent antiplatelet action compared with clopidogrel [8–17]. However, there is limited data on the effects of clopidogrel reloading vs. switching to prasugrel or ticagrelor in this group of HTPR patients. In pharmacodynamic study, in post-PCI patients exhibiting HTPR, prasugrel was more effective than a double maintenance dose of clopidogrel in reducing platelet reactivity (PR) [18]. Ticagrelor therapy was associated with greater platelet inhibition compared with clopidogrel in stable CAD patients with HTPR following a 300-mg clopidogrel loading dose [19]. In the present study, we aimed to com- pare the pharmacodynamic effects of clopidogrel reloading vs. switching to prasugrel or ticagrelor in clopidogrel resistant Indian pa- tients being taken up for PCI. 2. Methods Study was a prospective randomized, single-centre, 3-arm, parallel- design study to evaluate the pharmacodynamic response of clopidogrel Clinical Trials and Regulatory Science in Cardiology 13 (2016) 14–20 ⁎ Corresponding author at: Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. E-mail address: golf_pgi@yahoo.co.in (P.K. Goel). http://dx.doi.org/10.1016/j.ctrsc.2015.10.007 2405-5875/© 2015 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents lists available at ScienceDirect Clinical Trials and Regulatory Science in Cardiology journal homepage: http://www.elsevier.com/locate/ctrsc