Summary of findings 1. Antiplatelet drug compared to placebo in mixed populations (with or without pre‐existing antiplatelet therapy) for the prevention of cognitive decline and dementia in people with cerebral small vessel disease and no dementia.

Antiplatelet drug compared to placebo, in populations with mixed prevalence of antiplatelet drug use at baseline, for the prevention of cognitive decline and dementia in people with cerebral small vessel disease and no dementia
Patient or population: people with cerebral small vessel disease and no dementia either already on antiplatelet therapy or not Setting: outpatient services Intervention: adding antiplatelet therapy in populations where some participants may have been taking antiplatelet  Comparison: placebo
Outcomes	Impact	№ of participants (studies)	Certainty of the evidence (GRADE)
Change in cognitive function from baseline assessed with ADAS‐Cog, CIBIC‐plus, MMSE, CDR, CDR‐SB,	1 trial reported a beneficial effect across 2 of 5 cognitive outcomes (ADAS‐Cog and CIBIC‐plus), but the size of benefit may be less than the minimal important clinical difference.	280 (1 RCT)	⊕⊝⊝⊝ Very lowa,b,c
Incident dementia	No studies reported this outcome	—	—
Major bleeding (intracranial and extracranial)	1 trial reported no difference between treatment groups for this outcome.	280 (1 RCT)	⊕⊝⊝⊝ Very lowa,b,c
Functional ability	1 trial reported no difference in functional anility between treatment groups	280 (1 RCT)	⊕⊝⊝⊝ Very lowa,b,c
Stroke or transient ischaemic attack	1 trial reported no difference in stroke or transient ischaemic attacks between treatment groups	280 (1 RCT)	⊕⊝⊝⊝ Very lowa,b,c
Any adverse events (excluding major bleeding)	1 study reported no difference in adverse events between treatment groups	280 (1 RCT)	⊕⊝⊝⊝ Very lowa,b,c
Withdrawal from study medication	1 trial reported an increase in medication withdrawal in those taking additional antiplatelets in comparison to those taking a placebo (OR for withdrawal from treatment 1.88, 95% CI 0.90 to 3.42)	280 (1 RCT)	⊕⊝⊝⊝ Very lowa,b,c
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ADAS‐Cog: Alzheimer's Disease Assessment Scale – Cognitive Subscale; ADL: activities of daily living; CDR‐SB: Clinical Dementia Rating scale Sum of Boxes; CI: confidence interval; MMSE: Mini‐Mental State Examination; OR: odds ratio; RCT: randomised controlled trial.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded one level because all participants had cognitive impairment at baseline, making it difficult to translate these findings to the general small‐vessel disease population.
^bDowngraded one level as it is arguable whether DL‐3‐n‐butylphthalide should technically be classified as an antithrombotic therapy.
^cDowngraded one level for imprecision as only one study contributed to this finding.