Fast track — ArticlesCilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study
Introduction
Stroke is the second leading cause of mortality in China, with about 7 million people affected countrywide.1 Aspirin is effective for the prevention of secondary stroke and has been used in up to 89% of patients in China (REACH registry, unpublished data). However, although recurrent stroke is controlled by this treatment, the incidence of cerebral haemorrhage and other bleeding events is higher in China than in high-income countries.2 To overcome the risk of haemorrhage, combinations of antiplatelet drugs that act on different pathways have been used; these compounds were used effectively and safely in patients with unstable coronary heart disease, with the most benefits seen during the first few weeks of treatment.3 The results of recent studies have shown that the combination of two antiplatelet drugs failed to improve stroke prevention rates owing to the increased risk of bleeding events associated with their long-term use.4, 5 Bleeding due to antiplatelet drugs is an important clinical problem in primary6 and secondary stroke prevention, particularly in the Chinese population, which has a higher incidence of cerebral haemorrhage than other ethnic groups.7, 8
Cilostazol, a selective inhibitor of phosphodiesterase 3 (PDE3), prevents inactivation of the intracellular second messenger cyclic AMP and irreversibly inhibits platelet aggregation and vasodilation. In addition, cilostazol delays the onset of atherosclerosis,9 protects the vessel endothelium, inhibits the proliferation of arterial smooth-muscle cells,10, 11 and has shown efficacy in the prevention of ischaemic stroke in a group of patients from Japan.12 However, no studies have compared the efficacy of cilostazol with that of aspirin, which continues to be widely used to prevent secondary ischaemic stroke. We report the results of a trial to assess the efficacy and safety of cilostazol compared with aspirin in the prevention of secondary stroke in a small sample of patients, which could be a pilot study for a large phase III trial.
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Participants
720 patients (495 male and 225 female, mean age 60·2 years) were enrolled consecutively between May 1, 2004, and Dec 31, 2004. Follow-up was concluded on Dec 31, 2005. Patients were eligible for inclusion if they had had an ischaemic stroke within the preceding 1 to 6 months, their diagnosis had been confirmed with neuroimaging, and they had a modified Rankin scale score of less than 4 at enrolment. Exclusion criteria were one or more from a history of intracranial or subarachnoid haemorrhage,
Results
Treatment was given for a total of 740 person-years. The trial profile is shown in figure 1.
569 patients (79%) had vascular risk factors, including hypertension, diabetes, and high lipid concentrations. The profiles of the cilostazol patients and aspirin patients were similar (table 1), although baseline systolic blood pressure was significantly higher in the control group than in the cilostazol group (p=0·03) but this resolved after 1 month's treatment with antihypertensive drugs. 223 patients
Discussion
Cilostazol has similar effects to those of aspirin in the prevention of recurrent ischemic stroke during the first 6 months after starting treatment. By contrast, after 6 months, cilostazol was more effective than aspirin, and at the end of the study there was a 38·1% reduction in the relative risk of a primary endpoint in the cilostazol group compared with the aspirin group. However, this did not reach statistical significance, which, we feel, is due to the small sample size and the short
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