Zhang 2018.

Study characteristics
Methods	Appears to be single site study. 2x2 factorial design to telmisartan vs placebo and rosuvastatin vs placebo. All participants on hydrochlorothiazide. Randomisation: participants allocated using computer‐generated randomisation schedule in a 1:1:1:1 ratio. Participants blinded; providers blinded; unclear whether cognitive outcome assessors blinded. High rate of follow‐up. Duration of trial: 5 years.
Participants	Geographic region: Shangdong area, China. Study setting: community dwelling participants. N = 732 (47.8% female). Age range: ≥ 60 years; mean (SD) 70.7 (6.2) years. Ethnicity: all participants Han Chinese. BP entry criteria: 'SBP ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, or self reported use of blood pressure‐lowering medications in the last 2 weeks'. Mean BP at entry: 156/71 mmHg. Mean education: 7 years.
Interventions	Participants randomised to 'telmisartan vs. placebo, telmisartan 40 mg increased to 80 mg given once daily if needed...open‐label medication, hydrochlorothiazide (12.5 mg increased to 25 mg daily if needed), was used as a baseline medication in all treatment arms...Clinical follow‐up visits were conducted weekly during the washout period, and then at trial months 1, 3, and 6, and every 6 months thereafter, until the conclusion of the study...The targeted blood pressure was defined as <140/90 mm Hg. Medication compliance was assessed by counting the number of tablets taken.' Precise up‐titration steps unclear.
Outcomes	Analysed in the review: 'Cognitive function was assessed annually using the Chinese versions of the MMSE and the Mattis Dementia Rating Scale (DRS) by experienced neuropsychology research assistants, who are experts in the measurement of cognitive function...For the progression of cognitive impairment, the changes in scores of the MMSE and DRS and possible cognitive impairment were used. Possible cognitive impairment was identified using the following: an MMSE score of ≤23 points at any annual follow‐up visit or a decline by ≤3 points between any two annual follow‐up visits, and/or a DRS score ≤123 points at any annual follow‐up visit.' Not analysed in the review: WMH.
Notes	All participants received diuretic treatment 'open‐label medication, hydrochlorothiazide (12.5 mg increased to 25 mg daily if needed), was used as a baseline medication in all treatment arms'
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: 'We used a two‐by‐two factorial design to randomly assign eligible patients on a 1:1:1:1 ratio into antihypertensive intervention (telmisartan vs. placebo, telmisartan 40 mg increased to 80 mg given once daily if needed) and lipidmodulating intervention (rosuvastatin vs. placebo, rosuvastatin 10 mg given once daily) arms separately.'
Allocation concealment (selection bias)	Low risk	Quote: 'We used computer‐generated randomization according to the order of recruitment with a block size of eight, without stratification.'
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: 'Members of our institution who were not directly working on the study executed the randomization and supplied study medications. During the double‐blind phase, all patients and investigators were masked to treatment assignment.' Comment made that neuroradiologists interpreting the MRI images were blinded to clinical and cognitive patient data.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: 'Treatment allocations were not unmasked until the study was completed and after final clinical database lock down'. No mention made of blinding of the neuropsychology research assistants assessing cognition.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: 'Among the 732 patients...725 (99.0%), 714 (97.5%), 703 (96.0%), 686 (93.7%), and 676 (92.4%) completed the first, second, third, fourth, and fifth annual cognitive functional assessments, respectively, over a mean follow‐up time of 59.8 (range 12–65) months.The most common reasons for non‐complete of the trial were death (31, 55.4%), withdrawal (16, 28.6%), and loss to follow‐up (5, 5.4%).'
Selective reporting (reporting bias)	Low risk	Quote: 'Analyses followed the intention‐to‐treat principle.'
Other bias	High risk	HIgh risk contamination bias given that all participants in placebo group received diuretic therapy. Study powered to detect differences in WMH on MRI, not differences in cognitive decline between the groups.

CVD: cerebrovascular disease; MI: myocardial infarction; AST: aspartate aminotransferase; ALT: alanine aminotransferase; WMH: white matter hyperintensity.