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ȣ - 540061 146 |
| Inhibitory Interaction between Calcium-Channel Blocker and Clopidogrel: the Efficacy of Cilostazol to Overcome it : Lessons from the multicenter CILON-T trial |
| ¹ 서울대학교병원, ² 분당서울대학교병원, ³ 고대구로병원, ⁴건양대병원, 5 충북대병원 |
| ¹ 이승표, ² 서정원, ¹ 박경우, ¹ 이해영, ¹ 강현재, ¹ 구본권, ² 조영석, ² 연태진, ² 채인호, ² 최동주, ³ 라승운, ⁴권택근, ⁴배장호, 5 배장환, 5 조명찬, ¹ 김효수 |
Objective. We evaluated whether calcium-channel blockers (CCB) would negatively interact with clopidogrel in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents, and tested the efficacy of cilostazol to overcome such interaction.
Design and Main Outcome Measures. 902 patients were included for this post-hoc analysis of the multicenter, prospective, randomized CILON-T trial and divided into four groups depending on CCB prescription at discharge and type of anti-platelet regimen (double (DAT) versus triple (TAT, addition of cilostazol on DAT)) in a 2-by-2 factorial manner. Primary endpoint was a composite of cardiac death, nonfatal myocardial infarction and ischemic stroke at 6 months post-PCI. On-treatment platelet reactivity (OPR) was assessed by VerifyNow P2Y12 assay (PRU).
Results. Concomitant CCB use significantly increased OPR in DAT (251.2±73.8 vs. 225.6±82.3 for CCB users vs. CCB non-users, p=0.008), but not in TAT group (214.5±90.9 vs. 203.4±90.0 for CCB users vs. CCB non-users, p=0.294). Primary endpoint significantly increased by use of CCB in patients with DAT (4.8% vs. 0.9% for CCB users vs. CCB non-users, p=0.016), but not in those with TAT (0% vs. 1.8% for CCB users vs. CCB non-users, p=0.346). Addition of cilostazol on DAT significantly reduced OPR and clinical events in patients taking CCB (p=0.002 for PRU, p=0.027 for thrombotic events comparing CCB+DAT vs. CCB+TAT group). CCB without concomitant cilostazol use was a significant predictor of total thrombotic and also, early thrombotic events within one month.
Conclusions. Concomitant use of CCB may weaken the anti-platelet effect of clopidogrel, resulting in an increase of thrombotic events. This negative interaction between CCB and clopidogrel may be overcome by addition of cilostazol.
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|
Double anti-platelet (DAT) |
p-value* |
Triple anti-platelet (TAT) |
p-value† |
p-value‡ |
|
CCB(-)
(n=326) |
CCB(+)
(n=124) |
CCB(-)
(n=336) |
CCB(+)
(n=116) |
|
Cardiac death |
0 |
2.4 (3) |
0.021 |
0 |
0 |
… |
<0.001 |
|
Nonfatal MI |
0.6 (2) |
0.8 (1) |
>0.999 |
0.9 (3) |
0 |
0.573 |
0.779 |
|
Ischemic stroke |
0.3 (1) |
1.6 (2) |
0.185 |
0.9 (3) |
0 |
0.573 |
0.339 |
|
Stent thrombosis |
0.3 (1) |
3.2 (4) |
0.022 |
0.9 (3) |
0 |
0.573 |
0.019 |
|
Acute |
0 |
0 |
|
0.3 (1) |
0 |
|
|
|
Subacute |
0.3 (1) |
2.4 (3) |
|
0.6 (2) |
0 |
|
|
|
Late |
0 |
0.8 (1) |
|
0 |
0 |
|
|
|
Cardiac events (cardiac death + nonfatal MI) |
0.6 (2) |
3.2 (4) |
0.099 |
0.9 (3) |
0 |
0.566 |
0.048 |
|
All thrombotic events (cardiac death + nonfatal MI + ischemic stroke) |
0.9 (3) |
4.8 (6) |
0.016 |
1.8 (6) |
0 |
0.346 |
0.013 |
*, p-value of DAT+CCB(-) vs. DAT+CCB(+)
†, p-value of TAT+CCB(-) vs. TAT+CCB(+)
‡, p-value of all four groups compared together
|
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