Cilostazol + aspirin/clopidogrel may reduce recurrent ischaemic stroke risk
The addition of the phosphodiesterase 3 inhibitor cilostazol to either aspirin or clopidogrel reduced the risk of recurrent stroke among patients at high risk of recurrence following a non-cardioembolic ischaemic stroke, according to the CSPS.com* study conducted in Japan.
Eight to 180 days following the onset of a non-cardioembolic ischaemic stroke, 1,879 patients aged 20–85 years at high risk for stroke recurrence** who were on aspirin (81–100 mg) or clopidogrel (50–75 mg) treatment were randomized to continue receiving aspirin or clopidogrel alone (monotherapy; n=947, mean age 69.7 years, 27.9 percent female), or cilostazol (100 mg BID) plus either aspirin or clopidogrel (dual therapy; n=932, mean age 69.6 years, 31.7 percent female).
Over a median 17-month follow-up period, there were fewer incidences of ischaemic stroke recurrence among patients on dual therapy than those on monotherapy (4.7 percent vs 11.4 percent, hazard ratio [HR], 0.49, 95 percent confidence interval [CI], 0.31–0.76; p=0.0010). [ISC 2019, abstract LB3]
Patients on dual therapy also had a reduced risk of a composite of stroke, myocardial infarction, and vascular death compared with those on monotherapy (6.2 percent vs 21.4 percent, HR, 0.52, 95 percent CI, 0.35–0.77; p=0.0008), as well as reduced risks of any stroke (3.6 percent vs 7.5 percent, HR, 0.51; p=0.001), ischaemic stroke or transient ischaemic attack (3.4 percent vs 7.3 percent, HR, 0.50; p<0.001), and all vascular events (5.0 percent vs 9.5 percent, HR, 0.56; p=0.001). However, risk of haemorrhagic stroke (HR, 0.77; p=0.65) and all-cause mortality (HR, 0.92; p=0.88) was comparable between dual therapy and monotherapy recipients.
The incidence of severe or life-threatening bleeding was also comparable among dual therapy and monotherapy recipients (2.0 percent vs 2.7 percent, HR, 0.66, 95 percent CI, 0.27–1.60; p=0.3539).
Overall, adverse events (AEs) occurred more frequently among dual therapy compared with monotherapy recipients (27.4 percent vs 23.1 percent; p=0.038), specifically cardiac AEs (8.4 percent vs 1.8 percent; p<0.001), with 59 patients on dual therapy having palpitations or tachycardia. However, serious AEs were more common in the monotherapy group compared with the dual therapy one (15.0 percent vs 9.3 percent; p<0.001), particularly those affecting the nervous (8.3 percent vs 4.7 percent; p=0.002) or gastrointestinal system (1.2 percent vs 0.2 percent; p=0.022). Bleeding AEs also occurred at a similar rate, with 38 and 33 incidences in the dual therapy and monotherapy groups, respectively (4.1 percent vs 3.5 percent).
Although the combination of aspirin and clopidogrel has been shown to reduce the early risk of recurrent ischaemic stroke, long-term use has led to an increased risk of major bleeding, said the authors led by Dr Kazunori Toyoda, Deputy Director General of the Hospital, National Cerebral and Cardiovascular Center in Suita, Osaka, Japan.
“[In this study], the combination of cilostazol with aspirin or clopidogrel [led to] a lower risk of ischaemic stroke and a similar risk of severe or life-threatening bleeding compared with aspirin or clopidogrel alone [in patients with high risk of stroke recurrence],” they said, acknowledging that as the study was conducted in a Japanese population, these findings may not extend to other ethnicities.
“The addition of cilostazol to aspirin or clopidogrel is recommendable for long-term use in the chronic stage of high-risk non-cardioembolic stroke for patients who are tolerable to headache and palpitation,” said Toyoda and colleagues.