Yonsei Med J.  2013 Jan;54(1):34-40. 10.3349/ymj.2013.54.1.34.

Adjunctive Cilostazol versus High Maintenance Dose of Clopidogrel in Patients with Hyporesponsiveness to Chronic Clopidogrel Therapy

• Lee GY
• Hahn JY
• Lee SY
• Kim HJ
• Kim JH
• Lee SY
• Song YB
• Choi SH
• Choi JH
• Gwon HC

• KMID: 1776915
• DOI: http://doi.org/10.3349/ymj.2013.54.1.34

Abstract

PURPOSE
Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown.
MATERIALS AND METHODS
We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35).
RESULTS
Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0+/-10.2% versus 11.8+/-9.7%, p=0.61, and 286.3+/-54.7 versus 295.7+/-53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5+/-17.9% versus 28.3+/-16.6%, p=0.02, and 207.3+/-68.2 versus 241.3+/-76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7+/-8.7% to 15.8+/-18.4%, p=0.08, and from -18.6+/-58.0 to -61.9+/-84.3, p=0.08).
CONCLUSION
Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.

Keyword

Clopidogrel; cilostazol; platelets

MeSH Terms

Adult
Aged
Blood Platelets/drug effects
Cross-Over Studies
Drug Administration Schedule
Female
Humans
Male
Middle Aged
Platelet Aggregation Inhibitors/*administration & dosage
Prospective Studies
Receptors, Purinergic P2Y12/metabolism
Tetrazoles/*administration & dosage
Thrombosis/drug therapy
Ticlopidine/administration & dosage/*analogs & derivatives
Time Factors
Treatment Outcome
Platelet Aggregation Inhibitors
Receptors, Purinergic P2Y12
Tetrazoles
Ticlopidine

Figure

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  Fig. 1 Flow diagram of the study process. DES, drug-eluting stent.

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  Fig. 2 Percent inhibition of PRU and PRU at baseline and follow-up. (A) At baseline, group A and B showed no statistical difference in percent inhibition of PRU. After 4 weeks of randomization, group B showed significantly higher value of percent inhibition of PRU. (B) Group A and B initially presented no statistical difference in PRU. After 4 weeks of randomization, group B showed significantly lower value of PRU. (C) In the difference in percent inhibition, group B showed statistically larger change compared to group A after 4 weeks of antiplatelet regimens. (D) Group B showed the similar tendency of the larger change in PRU compared to group A after 4 weeks of antiplatelet regimens. PRU, P2Y12 reaction units.

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  Fig. 3 Data of the patients enrolled the followed crossover study. (A) Among the 12 patients enrolled crossover study, total 5 patients overcame clopidogrel hypo-responsiveness. (B) In change in percent inhibition of PRU from baseline, the crossover data showed a tendency of overall improved platelet inhibition. (C) In change in PRU from baseline, the patients also showed the larger degree of platelet inhibition in trend after the crossover. PRU, P2Y12 reaction units.

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