Hong Kong DHF.

Study characteristics
Methods	Study design: three‐arm, parallel RCT Centres: multicentre, no details Start of enrolment: not reported End of enrolment: not reported Mean follow‐up: 1 year Run‐in period: none
Participants	Inclusion criteria: "The inclusion criteria were age .18 years, clinical history of heart failure within 2 months prior to screening including a chest x ray demonstrating pulmonary congestion, NYHA functional class II – IV, left ventricular ejection fraction .45% by 2D‐echocardiography or a radionuclide technique, and therapy with diuretics with stable dose.14 days prior to recruitment." Exclusion criteria: "NYHA functional class I, myocardial infarction within 3 months, unstable angina within 1 month, significant valvular heart disease, uncontrolled hypertension, serious cardiac arrhythmias, concurrent therapy with calcium channel antagonist, b‐blockers (a‐methyl dopa was used for treating hypertension if required), positive inotropic agents (except digoxin for control of atrial fibrillation) and other angiotensin converting enzyme inhibitors or receptor blockers." Randomised (N): 151 ( intervention R: 45, intervention I: 56, control: 50) Withdrawn (N): for reasons other than death: intervention R: 6 (4 persistent irritating cough, 1 uncontrolled blood pressure, 1 refused to continue), intervention I: 1 due to onset of fast atrial fibrillation, control: 3 (1 uncontrolled high blood pressure, 1 defaulted, 1 refused to continue) Lost to follow‐up (N): 0 Analysed (N): 151 (intervention R: 45, intervention I: 56, control: 50) Age (years, mean, SD): intervention R: 74, 6.1; intervention I: 75, 8.5; control: 73, 8.4 Sex (% men): intervention R: 40; intervention I: 34; control: 42 Ethnicity (%): not reported Systolic blood pressure (mmHg, mean, SD): intervention R: 143, 22; intervention I: 145, 19; control: 145, 23 Heart rate (beats/min, mean, SD): intervention R: 79, 13; intervention I: 77, 9; control: 76, 14 BMI (mean, SD): intervention R: 26.8, 3.9; intervention I: 27.2, 4.1; control: 26.8, 4.2 Serum creatinine: not reported B‐type natriuretic peptide (pg/mL, mean, SEM): intervention R: 488, 701; intervention I: 568, 757; control: 566, 944 NT pro B‐type natriuretic peptide: not reported LVEF (%, median, IQR): intervention R: 65, 1; intervention I: 66, 1; control: 69, 2 NYHA class I (%): 0 NYHA class II (%): intervention R: 66.7; intervention I: 67.9; control: 72 NYHA class III (%): intervention R: 33.3; intervention I: 30.4; control: 28 NYHA class IV (%): 0 Hypertension (%): intervention R: 73; intervention I: 71; control: 76 Diabetes (%): intervention R: 22; intervention I: 18; control: 20 Atrial fibrillation (%): intervention R: 16; intervention I: 21; control: 10 Hospitalisation for HF: 100% as it was an inclusion criteria Coronary heart disease (%): intervention R: 18; intervention I: 11; control: 18 Stroke (%): not reported Diuretic (%): intervention R: Hydrocholorthiazide 8.9 furosemide 80 , dyazide 2.2; intervention I: Hydrocholorthiazide 10.7, furosemide 80.4 , dyazide 10.7; control: Hydrocholorthiazide 6, furosemide 68, dyazide 12 Digoxin (%): not reported Beta‐blocker (%): 0 ACEI (%): study drug (R) ARB (%): study drug (I) MRA (%): not reported
Interventions	Intervention R: "Ramipril was started at 2.5 mg daily and similarly titrated to 10 mg daily" Intervention I: "The initial dose of irbesartan was 18.75 mg daily which was titrated at 4 and 8 weeks to 75 mg daily." Comparator: usual care, "continue with diuretics alone" Concomitant medication: "Exclusion criteria were: ...concurrent therapy with calcium channel antagonist, b‐blockers (a‐methyl dopa was used for treating hypertension if required), positive inotropic agents (except digoxin for control of atrial fibrillation) and other angiotensin converting enzyme inhibitors or receptor blockers."
Outcomes	Planned: planned as per clinical trial registry entry: primary: 1. Number of hospital admissions for heart failure or mortality 2. Quality of life assessed by the Minnesota Quality of life Questionnaire 3. In ambulatory patients the exercise duration assessed by 6 min corridor walk test. Secondary: The incidence of side‐effects, effect on levels of natriuretic peptides, effect on doppler‐echocardiographic derived measurements of left ventricular diastolic function. Reported: cardiovascular mortality, hospitalisation for heart failure, all‐cause mortality, quality of life, 6MWT, blood pressure, NT‐proBNP, peak early diastolic mitral annular velocities, peak systolic velocity, LV mass
Notes	retrospective clinical trial registration
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"randomly allocated using computer‐generated random numbers in blocks of 10"
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	"All outcomes were reviewed blind to treatment allocation." "with blinded end point design"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	unable to assess
Selective reporting (reporting bias)	Unclear risk	retrospective clinical trial registration, no published protocol identified
Other bias	Unclear risk	"None of the authors received any lecture, advisory board, or consultancy fees relating to this study from the sponsors." "This study was initially supported by a small grant from the manufacturers of Irbesartan, who also donated the irbesartan medication (Sanofi‐Synthelabo). Design, conduct, retention of data, analysis and writing were all entirely independent and carried out by the authors only. Data were kept at the Chinese University of Hong Kong and are available for public scrutiny."