Clinical InvestigationCoronary Artery DiseasePlatelet reactivity in patients with chronic kidney disease receiving adjunctive cilostazol compared with a high-maintenance dose of clopidogrel: Results of the Effect of Platelet Inhibition According to Clopidogrel Dose in Patients with Chronic Kidney Disease (PIANO-2 CKD) randomized study
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Patients and study protocol
The PIANO-2 CKD clinical trial was a prospective, open, randomized platelet function study involving patients with CKD. Between September 2009 and June 2011, 74 consecutive CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease were enrolled in this study. To compare the levels of platelet aggregation according to renal function, 50 patients undergoing PCI for stable coronary artery disease were enrolled in the study as the control group. The exclusion criteria
Baseline patient characteristics
Baseline characteristics, cardiovascular risk factors, and concomitant medications of the study population are summarized in Table I. The CKD and control groups were similar with respect to age, gender, and cardiovascular risk factors. No significant differences were observed in the 3 CKD groups. All patients demonstrated full compliance with the study protocol.
Maximal platelet aggregation profiles
The baseline Aggmax values were not significantly different in the 3 CKD groups (Table II); however, the control group had
Responses to different antiplatelet treatments
The rate of HOPR was significantly lower in the adjunctive cilostazol group than in the 75 mg/d or 150 mg/d clopidogrel groups (12% vs 46% vs 32%, respectively; P < .05) (Figure 3). Similar results were obtained when 20 μmol/L ADP-induced Aggmax >50% was used to define suboptimal clopidogrel responders (32% vs 75% vs 68%, respectively; P < .05) (4). The post hoc analysis showed that there were no differences in the rates of HOPR and suboptimal clopidogrel responders between groups 1 and 2. Both
Platelet activation markers assay
Before treatment, there were no significant differences in the plasma sCD40L and sP-selectin levels in the 3 CKD groups. After 14 days of antiplatelet therapy, both platelet activation markers were significantly decreased in each group (Figure 4). However, the plasma sCD40L (271.0 ± 38.3 pg/mL) and sP-selectin (50.0 ± 10.5 ng/mL) levels were significantly lower in group 3 (P < .01) compared with groups 1 and 2. The changes in both platelet activation markers were significantly higher in group 3
Discussion
This is the first randomized, prospective study to assess platelet responsiveness to clopidogrel in patients with CKD undergoing chronic hemodialysis. The 3 major results of this study were as follows: (1) CKD patients had higher platelet reactivity compared with patients with normal renal function, (2) an increase in the clopidogrel maintenance dose from 75 to 150 mg did not result in further suppression of platelet aggregation, and 3) adjunctive cilostazol treatment intensified inhibition of
Disclosure
There are no potential conflicts of interest.
Acknowledgements
This study was supported by the program of Kyung Hee University for the young researcher in medical science (KHU-20100741). The authors thank our nurses for assistance in executing this study.
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