11 Aug 20. Featured Paper

Cilostazol for secondary prevention of stroke & cognitive decline: systematic review & meta-analysis.

Link to paper on AHA Journals, Stroke.

Authors

Caroline McHutchison, Gordon W. Blair, Jason P. Appleton, Francesca M. Chappell, Fergus Doubal, Philip M. Bath, Joanna M. Wardlaw

Abstract

Background & purpose: Cilostazol, a phosphodiesterase 3’ inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere.

In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair & astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression.

Methods: A systematic review & meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression.

Two reviewers searched for papers (January 1, 2019 to July 16, 2019) & extracted data.

We calculated Peto odds ratios (ORs) & 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses.

The review is registered (CRD42018084742).

Results: We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) & 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries.

Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57–0.81]; P<0.0001), hemorrhagic stroke (16 trials, n=9736, OR=0.43 [95% CI, 0.29–0.64]; P=0.0001), deaths (OR=0.64 [95% CI, 0.49–0.83], P<0.0009), systemic bleeding (n=8387, OR=0.73 [95% CI, 0.54–0.99]; P=0.04), but increased headache & palpitations, compared with placebo, aspirin, or clopidogrel.

Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, & in trials with larger proportions (>40%) of lacunar stroke.

Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance.

Conclusions: Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk.

However, most trials related to Asia-Pacific patients & more trials in Western countries should assess its effects on cognitive decline, functional outcome, & tolerance, particularly in lacunar stroke & other presentations of small vessel disease.

Keywords

• Aspirin

• Cilostazol

• Clopidogrel

• Meta-analysis

• Stroke

• Stroke, lacunar