Key result
Ticagrelor resulted in a markedly lower P2Y12 reactive unit value at 30 days compared to clopidogrel (32.6 vs. 203.7; P<0.001) in patients with CKD and NSTE-ACS.
Why the study?
Does ticagrelor improve platelet inhibition compared to clopidogrel in patients with NSTE-ACS and chronic kidney disease?
RCT (n=60)
1:1
No
Does ticagrelor improve platelet inhibition compared to clopidogrel in patients with NSTE-ACS and chronic kidney disease?
Absolute Event Rate: 32.6% vs 203.7%
p-value: p=< 0.001
Ticagrelor provides significantly more potent platelet inhibition than clopidogrel in patients with NSTE-ACS and chronic kidney disease, offering a mechanistic explanation for its greater clinical efficacy in this population.
Supports ticagrelor preference for potent platelet inhibition in CKD-NSTE-ACS; confirms mechanistic advantage over clopidogrel in this population.
Background Pivotal clinical trials found that ticagrelor reduced ischaemic complications to a greater extent than clopidogrel, and also that the benefit gradually increased with the reduction in creatinine clearance. However, the underlying mechanisms remains poorly explored. Methods This was a single‐centre, prospective, randomized clinical trial involving 60 hospitalized Adenosine Diphosphate (ADP) P2Y12 receptor inhibitor‐naïve patients with chronic kidney disease (CKD) (estimated glomerular filtration rate <60 ml min–1 1.73 m–2) and non‐ST‐elevation acute coronary syndromes (NSTE‐ACS). Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180 mg loading dose, then followed by 90 mg twice daily) or clopidogrel (600 mg loading dose, then followed by 75 mg once daily). The primary endpoint was the P2Y12 reactive unit (PRU) value assessed by VerifyNow at 30 days. The plasma concentrations of ticagrelor and clopidogrel and their active metabolites were measured in the first 10 patients in each group at baseline, and at 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after the loading dose. 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 at 2 h, 8 h and 24 h after the loading dose (P < 0.001). Ticagrelor and its active metabolite AR‐C124910XX showed a similar time to reach maximum concentration (Cmax) of 8 h, with the maximum concentration (Cmax) of 355 (242.50–522.00) ng ml–1and 63.20 (50.80–85.15) ng ml–1, respectively. Both clopidogrel and its active metabolite approached the Cmax at 2 h, with a similar Cmax of 8.67 (6.64–27.75) ng ml–1 vs. 8.53 (6.94–15.93) ng ml–1. Conclusion Ticagrelor showed much more potent platelet inhibition in comparison with clopidogrel in patients with CKD and NSTE‐ACS.
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Wang et al. (2017) conducted an RCT in Chronic kidney disease and non-ST-elevation acute coronary syndromes (n=60). Ticagrelor vs. Clopidogrel (600 mg loading dose, then 75 mg once daily) was evaluated on P2Y12 reactive unit (PRU) value assessed by VerifyNow at 30 days (p=< 0.001). Ticagrelor resulted in a markedly lower P2Y12 reactive unit value at 30 days compared to clopidogrel (32.6 vs. 203.7; P<0.001) in patients with CKD and NSTE-ACS.