STOCKHOLM – Adding cilostazol to a standard, dual-antiplatelet therapy regimen significantly cut platelet reactivity in patients, especially in those with diabetes, in a controlled study with 80 patients.
“Despite marked platelet inhibition, cilostazol does not change thrombin-mediated hemostasis, which may help explain its ischemic benefit without an increased risk of bleeding,” Dr. José Luis Ferreiro said at the Congress of the European Society of Cardiology.
Based on the new findings, cilostazol can have a role for “patients in whom you’d like more potent platelet inhibition who have a high risk for bleeding.” In addition, cilostazol treatment seems particularly appropriate for patients with diabetes, in whom it “works much better,” compared with patients without diabetes, It’s also well suited as a third antiplatelet agent in patients on dual-antiplatelet therapy with aspirin and clopidogrel who have peripheral artery disease, an approved indication for cilostazol treatment, said Dr. Ferreiro, a cardiologist at the University Hospital of Bellvitge in Barcelona. Cilostazol also has Food and Drug Administration approval to prevent thromboembolism in patients with coronary stents.
Despite data like these that show incremental value from adding cilostazol to a dual-antiplatelet regimen, the drug remains largely unused in Western countries, probably because most of the evidence supporting its efficacy comes from Asian studies, especially from Korean researchers, Dr. Ferreiro said. In addition, about a quarter of patients do not tolerate cilostazol treatment because of adverse effects. Common adverse events include headache and diarrhea. Despite these drawbacks, cilostazol may be an attractive addition for antiplatelet therapy, compared with the new antiplatelet drugs prasugrel and ticagrelor, when drug cost is a consideration or for patients at high risk for bleeding complications, he said in an interview.
Dr. Ferreiro and his associates ran the new study to assess cilostazol’s ability to reduce platelet reactivity in 40 patients with diabetes (including some with type 1 and some with type 2 disease), compared with 39 patients without diabetes. The patients all had stable coronary artery disease and averaged 61 years old; about two-thirds were men.
All enrolled patients had received 81-mg aspirin and 75-mg clopidogrel daily for a month, and remained on dual-antiplatelet therapy during the study. The researchers randomized the patients to either 100-mg cilostazol twice daily or placebo daily for 2 weeks, followed by a 1 week washout and then a crossover to another 2 weeks of treatment with the alternative agent. The study’s primary end point was the difference in the reactivity of the platelet P2Y12 receptor, measured in a vasodilator-stimulated phosphoprotein (VASP) flow-cytometry assay, at the end of 2 weeks of treatment with either cilostazol or placebo.
Patients with diabetes averaged 53% on the P2Y12 reactivity index (PRI) while on placebo and 30% while on cilostazol, a 23% absolute, average drop in PRI attributable to cilostazol, a statistically significant effect. Patients without diabetes averaged 48% on placebo and 33% on cilostazol, a 15% absolute, average drop in their PRI attributable to cilostazol, also statistically significant. The difference in the average impact that cilostazol had on PRI between the patients with diabetes and those without diabetes (a 23% reduction vs. a 15% drop), also reached statistical significance, Dr. Ferreiro said.
Other assays of platelet reactivity that the researchers used as secondary end points showed similar results. The study did not include enough patients to determine whether cilostazol had different effects in patients with type 1 and type 2 diabetes.
Dr. Ferreiro said that he had no disclosures.