Pharmacodynamics and Pharmacokinetics of Ticagrelor Versus Clopidogrel in Patients with Acute Coronary Syndromes and Chronic Kidney Disease

Abstract

Background

Pivotal clinical trials found ticagrelor reduced ischemic complications to a greater extent than clopidogrel and what is more, the benefit gradually increased with the reduction on creatinine clearance. However, the underlying mechanisms remains poorly explored.

Methods

This is a single-center, prospective, randomized clinical trial involving 60 hospitalized P2Y12 inhibitor naïve patients with CKD (eGFR<60ml/min/1.73m²) and NSTE-ACS. Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor(180 mg loading dose, then 90 mg twice daily followed) or clopidogrel(600 mg loading dose, then 75 mg qd followed). The primary endpoint was the P2Y12 reactive unit (PRU) tested by VerifyNow at 30 days. Plasma concentration of ticagrelor and clopidogrel and its active metabolite was measured in first 10 patients in each group at baseline, and 1h, 2h, 4h, 8h, 12h and 24h after loading does.

Results

Baseline characteristics were well matched between the two groups. Our results indicated a markedly lower PRU in patients treated with ticagrelor vs. clopidogrel at 30 days (32.6±11.29 vs 203.7±17.92, P<0.001) as well as 2, 8 and 24 hours after loading does (P<0.001). Ticagrelor and its active metabolite AR-C124910XX showed similar T_max(h) of 8h, with C_max(ng/ml) of 355(242.50-522.00) and 63.20(50.80-85.15), respectively. Both Clopidogrel and its active metabolite approached maximal plasma concentration at 2 hours, with close C_max(ng/ml) of 8.67(6.64-27.75) vs 8.53(6.94-15.93).

Conclusion

Ticagrelor showed much more potent platelet inhibition in comparison of clopidogrel in patients with NSTE-ACS and CKD.

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