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-1 and 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.
RCT Entities:
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-1 and 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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