International Stroke Conference

International Stroke Conference

February 06, 2019
3 min read

Adding cilostazol to antiplatelet therapy reduces recurrent ischemic stroke risk

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Kazunori Toyoda
Kazunori Toyoda

Stroke survivors who had cilostazol added to aspirin or clopidogrel had reduced risk for recurrent ischemic stroke compared with patients taking aspirin or clopidogrel alone, according to results from the study presented at the International Stroke Conference.

Dual antiplatelet therapy with aspirin and clopidogrel has been shown to reduce short-term risk for recurrent stroke, but in the long term, has not been effective and has increased bleeding risk, Kazunori Toyoda, MD, PhD, deputy director general at the National Cerebral and Cardiovascular Center in Suita, Osaka, Japan, said during a presentation.

“Cilostazol, a phosphodiesterase [type] 3 inhibitor, prevents stroke recurrence with relatively low incidence of serious bleeding,” he said. “Dual antiplatelet therapy involving cilostazol may be safe and appropriate for long-term use.”

Previous studies found that cilostazol (Pletal, Otsuka) reduced risk for recurrent stroke compared with placebo, reduced risk for any stroke or major bleeding compared with aspirin, he said.

For the present study, Toyoda and colleagues evaluated whether cilostazol plus aspirin or clopidogrel reduced recurrent ischemic stroke risk in the chronic phase compared with aspirin or clopidogrel alone. The researchers enrolled 1,879 Japanese patients with ischemic stroke 8 to 180 days before enrollment; in the dual-therapy group, the mean age was 70 years and 32% were women; in the monotherapy group, the mean age was 70 years and 28% were women.

The primary efficacy outcome was recurrent ischemic stroke. Safety outcomes included severe or life-threatening bleeding according to GUSTO classification, intracranial hemorrhage, any adverse events, serious adverse events and bleeding adverse events.

At 4 years, the primary efficacy outcome occurred in 29 patients (annualized rate, 2.2%) of the dual-therapy group and 64 patients (annualized rate, 4.5%) of the monotherapy group (HR = 0.49; 95% CI, 0.31-0.76), Toyoda said.

The composite of stroke, MI and vascular death at 4 years occurred in 38 patients (annualized rate, 2.9%) of the dual-therapy group and 78 patients (annualized rate, 5.5%) of the monotherapy group (HR = 0.52; 95% CI, 0.35-0.77).

The dual-therapy group compared with the monotherapy group at 4 years also had lower rates of any stroke (HR = 0.51; 95% CI, 0.34-0.77), ischemic stroke or transient ischemic attack (HR = 0.5; 95% CI, 0.33-0.76) and any vascular event (HR = 0.56; 95% CI, 0.39-0.8), although there were no differences in hemorrhagic stroke or all-cause mortality, Toyoda said.

The results did not vary across subgroups.


There were no differences between the groups in severe or life-threatening bleeding or intracranial hemorrhage (HR for both = 0.66; 95% CI, 0.27-1.6), according to the researchers.

Total adverse events were higher in the dual-therapy group (27.4% vs. 23.1%; P = .038), driven by cardiac adverse events such as palpitation and tachycardia (8.4% vs. 1.8%; P < .001), Toyoda said.

Serious adverse events, including efficacy outcomes such as stroke, were higher in the monotherapy group (9.3% vs. 15%; P < .001), driven by nervous system events (4.7% vs. 8.3%; P = .002) and gastrointestinal events (0.2% vs. 1.2%; P = .022), whereas bleeding adverse events did not differ between the groups, he said.

“In patients with high-risk stroke recurrence, the combination of cilostazol with aspirin or clopidogrel had a lower risk of ischemic stroke and a similar risk of severe or life-threatening bleeding compared to aspirin or clopidogrel alone,” Toyoda said. “The addition of cilostazol to aspirin or clopidogrel is recommendable for the long-term use in the chronic stage of high-risk non-cardioembolic stroke for patients who are tolerable to headache and palpitation.” – by Erik Swain


Toyoda K, et al. LB3. Presented at: International Stroke Conference; Feb. 5-8, 2019; Honolulu.

Disclosure: The study was supported by Otsuka. Toyoda reports he received consultant fees from Otsuka.