SUPPORT.

Study characteristics
Methods	Study design: parallel, individual RCT Centres: 17, Japan Start of enrolment: October 2006 End of enrolment: March 2010 Median follow‐up: 4.4 years Run‐in period: not reported
Participants	Inclusion criteria: The inclusion criteria of the present study were designed to enroll symptomatic CHF patients with hypertension aged 20 to 79 years who were treated with ACEI or beta‐blocker or both. Inclusion criteria: NYHA Classes II to IV CHF, History of hypertension or treated with anti‐hypertensive medications, Aged 20 or older and, 80 years at the entry, Stable with angiotensin‐converting enzyme inhibitors and/or b‐blockers, Not treated with angiotensin II receptor blockers Exclusion criteria: The exclusion criteria were designed to exclude patients with substantive confounding medical conditions or an inability to meaningfully participate in the SUPPORT trial. Exclusion criteria: Patients who have renal dysfunction (serum creatinine ≥3.0 mg/dL), or those who are under chronic haemodialysis, Drug hypersensitivity to olmesartan, Severe liver dysfunction, History of angioedema, History of malignant tumour or life‐threatening illness of poor prognosis, Pregnant or possibly pregnant patients, Cardiovascular surgery within 6 months prior to the date of the entry, Acute myocardial infarction within 6 months prior to the date of the entry, Percutaneous coronary intervention with or without stent implantation within 6 months prior to the date of the entry. Randomised (N): 1146 (1 patient excluded prior to this for protocol violation) (578 intervention, 568 control) Withdrawn (N): for reasons other than death 9 (1 protocol violation, 8 no LVEF data) Lost to follow‐up (N): not reported Analysed (N): Total 1138 (HFpEF 709, HFrEF 429) (HFpEF 363 intervention, HFpEF 346 control) Age (years, mean, SD): intervention: 66.5, 10.1; control: 65.9, 9.7 Sex (% men): intervention: 70.2; control: 71.1 Ethnicity (%): not reported Systolic blood pressure (mmHg, mean, SD): intervention: 131.5, 17.1; control: 130.1, 17.1 Heart rate (beats/min, mean, SD): intervention: 70.6, 13.2; control: 71.4, 14.9 BMI (mean, SD): intervention: 24.4, 4.2; control: 24.8, 4.2 Serum creatinine (mg/dL, mean, SD): intervention: 0.9, 0.3; control: 0.9, 0.3 B‐type natriuretic peptide (pg/mL, median, IQR): intervention: 71.1 (30.2, 148.0); control: 58.7 (27.5, 139.0) NT pro B‐type natriuretic peptide (pg/mL): not reported LVEF (%, mean, SD): intervention: 63.8, 8.8; control: 63.1, 8.6 NYHA class I (%): 0 NYHA class II (%): intervention: 94.2; control: 93.4 NYHA class III (%): intervention: 5.5; control: 6.4 NYHA class IV (%): 0 Hypertension (%): 100 Diabetes (%): intervention: 46.6; control: 53.9 Atrial fibrillation (%): not reported Hospitalisation for heart failure (%): intervention: 52.2; control: 44.1 Coronary heart disease (%): intervention: 48.8; control: 45.1 Stroke (%): not reported Diuretic (%); intervention: 45.7; control: 48.0 Digoxin (%): not reported Beta‐blocker (%): intervention: 63.4; control: 65.4 ACEI (%): intervention: 79.9; control: 79.0 ARB (%): study drug MRA (%): intervention: 18.5; control: 22.0
Interventions	Intervention: olmesartan. "Olmesartan was initiated at a dose of 5–10 mg/day, and then up titrated to 40 mg/ day, if tolerable, in the olmesartan group, while no ARB use was allowed in the control group" Comparator: no treatment Concomitant medication: treated with ACEI and/or beta‐blocker in inclusion criteria, not treated with ARB
Outcomes	Planned: Clinical trial registry entry at point of enrolment: primary outcomes all‐cause death, nonfatal acute myocardial infarction, nonfatal stroke, hospital admission due to congestive heart failure Reported: Primary Endpoint: A composite of the following outcomes: all‐cause death, non‐fatal acute myocardial infarction, non‐fatal stroke, hospital admission due to worsening heart failure Secondary Endpoints: cardiovascular death, death due to heart failure, sudden death, acute myocardial infarction, stroke, hospital admission from any cardiovascular reasons, fatal arrhythmia or appropriate ICD discharge, new‐onset diabetes, development of renal dysfunction (equal to or more than twofold increase of serum creatinine level), new‐onset atrial fibrillation, a need to modify treatment procedures for heart failure, a decrease in left ventricular ejection fraction (equal to or more than 20% decrease), an increase in B‐type natriuretic peptide levels (> 2‐fold increase if the baseline level was > 50 pg/mL and an increase of > 100 pg/mL if the baseline level was < 50 pg/mL), changes in serum markers for metabolic syndrome (high sensitive C‐reactive protein, adiponectin, microRNAs）
Notes	Emailed investigators to ask for outcome date for participants with LVEF > 40%. No response. Published (and presented above) are baseline characteristics and results for HFpEF as defined by investigators (LVEF ≥ 50%).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	not reported
Allocation concealment (selection bias)	Unclear risk	not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	open label
Blinding of outcome assessment (detection bias) All outcomes	Low risk	blinded endpoint study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	withdrawals reported with reasons, not detailed by treatment arm ITT used, but after exclusion of some randomised patients
Selective reporting (reporting bias)	Low risk	primary outcomes reported as planned
Other bias	Low risk	"The Department of Evidence‐based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, is supported in part by the unrestricted research grants from Daiichi Sankyo Co, Ltd (Tokyo, Japan), Bayer Yakuhin, Ltd (Osaka, Japan), Kyowa Hakko Kirin Co, Ltd (Tokyo, Japan), Kowa Pharmaceutical Co, Ltd (Tokyo, Japan), Novartis Pharma K.K. (Tokyo, Japan), Dainippon Sumitomo Pharma, Co, Ltd (Osaka, Japan), and Nippon Boehringer Ingelheim Co, Ltd (Tokyo, Japan). H.S. has received lecture fees from Bayer Yakuhin, Ltd (Osaka, Japan), Daiichi Sankyo Co, Ltd (Tokyo, Japan) and Novartis Pharma K.K. (Tokyo, Japan)." "This study was supported in part by the grants‐in‐aid from the Ministry of Health, Labour, and Welfare and those from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Funding to pay the Open Access publication charges for this article was provided by the author."