ALPINE 2003.

Study characteristics
Methods	Double‐blind, randomized, controlled, parallel‐group trial
Participants	392 patients from Sweden with hypertension (SBP 140 to 179 mmHg and/or DBP 90 to 104 mmHg), no severe concomitant disease including diabetes Mean age 55 years 207 F:185 M
Interventions	Candesartan 16 mg daily Hydrochlorothiazide 25 mg daily
Outcomes	BP at 1 year Patient well‐being (subjective symptom assessment) Plasma glucose, serum insulin, OGTT Total plasma cholesterol, LDL‐C, HDL‐C, triglycerides AEs leading to withdrawal or change in therapy Duration: 12 months
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study indicates that participants were randomly allocated to treatment groups, but no further information provided regarding the method of randomization.
Allocation concealment (selection bias)	Unclear risk	No description of allocation concealment was provided.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Study was described as double‐blind (including add‐on treatment), but no additional details provided.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No description of outcome assessment blinding was provided.
Incomplete outcome data (attrition bias) All outcomes	Low risk	An intention‐to‐treat approach was used. Quote: "The discontinuation rates were low, 8.2 and 7.1% [for candesartan and hydrochlorothiazide], respectively." One patient was excluded from ITT due to lack of outcome data. PP analysis also reported. No patients were lost to follow‐up.
Selective reporting (reporting bias)	Low risk	Although there was no evidence of selective reporting and all outcomes in methods were reported, it is not possible to fully assess without a protocol that confirms the list of prespecified outcomes.
Use of supplemental drugs	High risk	Supplemental drugs differed between groups. Quote: "If sitting systolic or diastolic blood pressure was above the target pressure at any visit during the treatment period, double‐blind treatment with 2.5–5.0 mg felodipine extended‐release was added to the candesartan group and 50–100 mg atenolol was added to the hydrochlorothiazide group. No further antihypertensive treatment was allowed."
Industry sponsorship	High risk	Quote: "The study was financed by the Department of Public Health and Clinical Medicine, Umea University, Sweden together with AstraZeneca R&D, Molndal, Sweden and Hassle Lakemedel AB, Sweden"