Cilostazol in Acute Ischemic Stroke Treatment (CAIST Trial): A Randomized Double-Blind Non-Inferiority Trial

Abstract

Background: Aspirin is a proven antiplatelet agent in acute ischemic stroke, and there are no current guidelines for other antiplatelet treatments. We aimed to compare the efficacy and safety of cilostazol with aspirin in acute stroke. Methods: Patients with measurable neurological deficits (NIHSS score ≤15) within 48 h of onset were randomly assigned to cilostazol (200 mg/day) or aspirin (300 mg/day) for 90 days. The primary endpoint was a modified Rankin Scale (mRS) score of 0–2 at 90 days. Cardiovascular events, bleeding complications, and other functional outcomes were also assessed. Statistical analysis was carried out by intention-to-treat and per-protocol bases. This trial is registered with ClinicalTrials.gov (NCT00272454). Results: In total, 458 patients were enrolled (mean age of 63 years, median NIHSS of 3), and mRS at 90 days was obtained in 447 patients. The primary endpoint was achieved in 76% (173/228) of those randomized to cilostazol and in 75% (165/219) assigned to aspirin, which supported the pre-specified non-inferiority of cilostazol to aspirin (95% CI of proportion difference: –6.15 to 7.22%, p = 0.0004). These results were also supported by per-protocol analysis (p = 0.045). Cardiovascular events occurred in 6 patients (3%) treated with cilostazol, and in 9 patients (4%) treated with aspirin (p = 0.41). Adverse events were more common in cilostazol-treated patients during the trial (91 vs. 85%, p = 0.055), while the frequencies of bleeding complications (cilostazol 11%, aspirin 13%, p = 0.43) or drug discontinuation (cilostazol 10%, aspirin 7%, p = 0.32) were not different. Conclusion: Cilostazol is feasible in acute ischemic stroke, and comparable to aspirin in its efficacy and safety.

Comparison of Antiplatelet and Antithrombotic Therapy for Secondary Prevention of Ischemic Stroke in Patients With Peripheral Artery Disease

“…It significantly reduced the rate of recurrent stroke and had lower hemorrhagic events compared with aspirin in the CSPS 2 trial in Japan. 15,19, 20 Our results similarly showed that cilostazol significantly reduced (21%) the risk of ischemic stroke, with similar safety to aspirin for Taiwanese patients with PAD and CVD. We consider that the Abbreviations as in Tables 1-3.…”

Nitric Oxide: Considerations for the Treatment of Ischemic Stroke

“…Use of PDE inhibitors in the early postischemic phase is currently not recommended due to a possibly increased bleeding risk by PDEinduced platelet inhibition. However, a recently completed clinical trial with cilostazole (CAIST: Cilostazol in acute ischemic stroke treatment (Lee et al, 2011)) showed that cilostazol is comparable to aspirine in terms of safety and bleeding complications so further clinical evaluation of cilostazol mono-or combination-therapy in acute stroke is ongoing (Nakamura et al, 2011).…”

Effect of a 4-Week Treatment with Cilostazol in Patients with Chronic Tinnitus: A Randomized, Prospective, Placebo-controlled, Double-blind, Pilot Study

“…Second, considering the etiological heterogeneity of acute hearing loss and tinnitus, administration of cilostazol for acute vascular insufficiency may have a role in the treatment of acute tinnitus. Indeed, clinical trials of cilostazol have shown beneficial effects on treatment for acute cardiovascular disease, acute renal dysfunction, and acute ischemic stroke [31,32] .…”

“…In two large prospective clinical studies of cilostazol, the incidences of headache development were reported to be 24% and 50.6% [29,31] . According to recent studies, cilostazol induced migraine-like headache in most of the participants without any history of migraine, and this phenomenon is believed to be due to intracellular cAMP accumulation [33,34] .…”