Abstract
Background and aims
Cilostazol is a phosphodiesterase-3 inhibitor with antiplatelet and pleiotropic vascular effects that may benefit cerebral small vessel disease (CSVD). Evidence for its role in secondary prevention of stroke and cognitive decline is limited but evolving. We updated a previous systematic review (from 2019) to evaluate the effects of cilostazol on recurrent stroke and cognition.
Methods
The protocol was registered on PROSPERO and conducted according to PRISMA guidelines. MEDLINE and EMBASE were searched from January 2019 to March 2025 for randomised controlled trials (RCTs) of cilostazol in adults with stroke, CVSD, or cognitive impairment. Meta-analyses and sensitivity analyses were performed where appropriate, combining data from the previous review.
Results
Sixteen publications were identified since 2019, including nine new RCTs in: stroke (4), chronic CSVD (3), mild cognitive impairment (1) and carotid stenosis (1). In meta-analyses (n=13,853), cilostazol, alone or plus other antiplatelets, reduced recurrence of ischemic (OR 0.70[0.59,0.82]) and haemorrhagic stroke (OR 0.60[0.40,0.89]), the ischemic stroke reduction mainly attributable to longer-duration (OR 0.67[0.56,0.80])studies or with >40% lacunar stroke (OR 0.64[0.52,0.79]). Cilostazol increased headache (OR 2[1.78,2.25]), palpitation (OR 2.05[1.71,2.45]) and diarrhoea (OR 2.35[1.97,2.82]). It did not improve MMSE scores (SMD -0.21[-0.33, -0.08]), largely driven by one large secondary analysis, but showed a trend towards reduced cognitive deterioration (RR 0.89[0.73,1.09]) and improved mood (SMD -0.16 [-0.40,0.08]).
Conclusions
Cilostazol appears effective and safe for long term secondary stroke prevention, including after lacunar stroke, while its effects on cognition and mood require confirmation in further randomised trials.
Conflict of interest
Yulu Shi, Mona Eskandaripour, Joanna Wardlaw: nothing to disclose