Hypothesis: The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for non-cardioembolic stroke patients within 48 h of symptom onset.
Methods: ADS is an investigator initiated, a prospective, multicenter (34 hospitals in Japan), randomized, and an aspirin-controlled study. Acute stroke patients with non-cardioembolic stroke within 48 hours of onset were studied. Only patients with preadmission mRS score 0-2 were included. Subjects were randomly allocated to the combination therapy with aspirin 81-200mg plus cilostazol 200mg (Dual group) and the single therapy with aspirin 81-200mg (Aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200mg for 3 months. Primary outcomes include 1) the neurological worsening within 14 day of onset; and 2) the rates of transient ischemic attack (TIA), stroke recurrence, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) within 14 days of onset. Secondary outcome included mRS score at 3 months after stroke.
Results: 1,201 patients (796 [66%] men; median age [interquartile range], 69 [61-77] years) were randomized 1:1 to either the dual group or the aspirin group. Initial National Institutes of Health Stroke Scale score was similar as 2 (1-4) in both groups (p=0.617). As a primary outcome, the neurological worsening within 14 days was similarly observed in the dual and in the aspirin group (10.5% vs. 9.7%, P=0.701). The rates of TIA and stroke recurrence in the dual and in the aspirin group were also similar as 0.2% vs. 0.2% (p=1.000), and 1.2% vs. 1.3% (p=1.000), respectively. As a safety outcome, each group had one patient with ICH (0.2% vs. 0.2%, p=1.000). Only 1 patient (0.2%) in the dual group complained of SAH within 14 days of stroke onset, though it was asymptomatic (p=1.000). Regarding the secondary outcome, although preadmission mRS score of 0 was infrequent in the dual group (84% vs. 89%, p=0.054), the rate of mRS 0-1 at 3 months seemed to be frequent in the dual group than aspirin group (69% vs. 64% p=0.075).
Conclusions: Dual antiplatelet therapy using cilostazol and aspirin does not reduce the rate of short-term neurological worsening. However, this combined therapy may improve the clinical outcome at 3 months of onset.