Adjunctive Cilostazol Improves Ischemic Outcomes in Carotid Artery Stenting Patients

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Adding cilostazol to standard dual antiplatelet therapy (DAPT) in clopidogrel-resistant patients undergoing carotid artery stenting (CAS) reduces resistance and suppresses the formation of new ipsilateral ischemic lesions, according to a study published online November 14, 2013, ahead of print in the Journal of Vascular Surgery. The results suggest the benefit of prescreening for clopidogrel resistance.

Researchers led by Ichiro Nakagawa, MD, PhD, of Nara Medical University (Nara, Japan), enrolled 64 consecutive patients with carotid artery stenosis who received clopidogrel 75 mg and aspirin 100 mg for more than 4 weeks before undergoing CAS in 2 time periods:

  • Period 1, 2010-2011 (n = 28): Patients received standard DAPT
  • Period 2, 2011-2013(n = 36): Patients received standard DAPT and were assessed for platelet function preoperatively using the VerifyNow P2Y12 assay (Accumetrics; San Diego, CA), and the 13 deemed to have clopidogrel resistance received adjunctive cilostazol 200 mg

Baseline clopidogrel resistance did not differ between periods 1 and 2 (43% vs. 36%; P = 0.615), but there were improvements in both PRUs and percent inhibition with platelet function testing at 30 days in period 2 (P = 0.044 and P = 0.002, respectively). The addition of cilostazol among clopidogrel resistant patients in period 2 reduced PRUs from 300 to 240 (P = 0.006) and increased percent inhibition from 8.8% to 28% (P = 0.005).

There were no symptomatic thromboembolic or hemorrhagic events in either group; however, there was a lower incidence of new ipsilateral ischemic lesions in period 2 compared with period 1 (6% vs. 23%; P = 0.034).

Triple Better than Double?

“We demonstrated for the first time that adjunctive cilostazol in patients with clopidogrel resistance suppresses the frequency of new cerebral ischemic lesions without increasing hemorrhagic complications,” Dr. Nakagawa and colleagues write.

The findings only add to a growing body of literature on the improved outcomes associated with cilostazol, they observe. Other studies have shown reduced rates of hemorrhagic complications and noninferiority to aspirin in preventing recurrent stroke. Also, a meta-analysis of triple antiplatelet therapy with cilostazol found a reduced rate of major adverse cardiac events vs. DAPT in coronary stenting patients, the authors report.

In an e-mail communication, Carl J. Lavie, MD, of the University of Queensland School of Medicine (New Orleans, LA), told TCTMD he was not surprised by the results given cilostazol’s favorable profile when added to DAPT in other studies.

Although the study “suggests benefits of cilostazol and has statistically significant results, [it] is rather small, so it should be considered exploratory rather than definitive. I would have no objections, however, with adding cilostazol to DAPT, since it is not expensive and has virtually no toxicity,” he said, noting that an exception would be in patients with significant congestive heart failure.

In spite of the observational design and small size of the study, the authors “recommend that antiplatelet management should be based on the evaluation of antiplatelet resistance for prevention of perioperative thromboembolic and hemorrhagic events in [carotid artery stenting].”


Nakagawa I, Wada T, Park HS, et al. Platelet inhibition by adjunctive cilostazol suppresses the frequency of cerebral ischemic lesions after carotid artery stenting in patients with carotid artery stenosis. J Vasc Surg. 2013;Epub ahead of print.



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  • Dr. Nakagawa reports no relevant conflicts of interest.
  • Dr. Lavie reports serving as a speaker and consultant for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer.

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