Zi 2003.

Study characteristics
Methods	Study design: parallel, individual, RCT Centres: 1, Royal Liverpool and Broadgreen University Hospitals Start of enrolment: 1997 End of enrolment: 1999 Follow‐up: 6 months Run‐in period: mentioned but no details
Participants	Inclusion criteria: "aged 65 years or older, with heart failure" "They all had left ventricular ejection fraction (LVEF) on echocardiography or radionuclide ventriculography equal or greater than 40%. Where a left ventricular ejection fraction could not be measured systolic function had to be preserved or only mildly impaired by direct visualisation of the echocardiograms" Exclusion criteria: "Patients with haemodynamically significant valvular disease, pulmonary hypertension, right ventricular systolic dysfunction, uncontrolled atrial fibrillation or flutter, unstable angina pectoris, hypotension, myocardial infarction within one month, renal failure (serum creatinine >150 mmol/L), renal‐artery stenosis, severe liver or pulmonary disease were excluded. patients treated with tetracyclines, lithium, benzodiazepines, major tranquillisers, anti‐depressants (with the exception of selective serotonin re‐uptake inhibitors) or major psychoactive drugs were also excluded." Randomised (N): 74 (36 intervention, 38 control) Withdrawn (N): for reasons other than death 4 (0 intervention, 4 control (worsening heart failure)) Lost to follow‐up (N): not reported Analysed (N): 74 (36 intervention, 38 control) Age (years, mean, SD): intervention: 77, 7; control: 78, 7 Sex (% men): intervention: 38.9; control: 31.6 Ethnicity (%): not reported Systolic blood pressure not reported Heart rate not reported BMI not reported Serum creatinine not reported B‐type natriuretic peptide not reported NT pro B‐type natriuretic peptide not reported LVEF not reported NYHA class I (%): intervention: 5.5; control: 0 NYHA class II (%): intervention: 77.8; control: 73.7 NYHA class III (%): intervention: 16.7; control: 26.3 NYHA class IV (%): 0 Hypertension (%): intervention: 27.8; control: 31.6 Diabetes (%): intervention: 11.1; control: 18.4 Atrial fibrillation (%): intervention: 38.9; control: 31.6 Hospitalisation for heart failure: not reported Coronary heart disease (%): intervention: 55.6; control: 57.9 Stroke (%): not reported Diuretic (%); intervention: 94.4; control: 97.1 Digoxin (%): intervention: 38.9; control: 26.3 Beta‐blocker (%): intervention: 19.4; control: 7.9 ACEI (%): study drug ARB (%): not reported MRA (%): not reported
Interventions	Intervention: quinapril. "Both drugs were titrated at two‐week intervals from 5 mg to 40 mg daily or equivalent within the first six weeks." Comparator: placebo Concomitant medication: "All patients continued concomitant treatment with diuretics, nitrates, digitalis glycosides, calcium channel blockers, and beta‐blockers as appropriate without change of dose except for diuretics. Therapy with ACE inhibitors for heart failure was withdrawn at least two weeks prior to the run‐in period."
Outcomes	Planned: we are not aware of a published protocol or pre‐registered clinical trial registry entry Reported: 6‐minutes walking distance, hypotension, worsening heart failure, changes of electrolytes, adverse events, quality of life, deaths, heart failure hospitalisation, hyperkalaemia
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	randomised, but no further detail
Allocation concealment (selection bias)	Unclear risk	not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	double‐blind, matching placebo
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	withdrawals due to worsening heart failure reported
Selective reporting (reporting bias)	Unclear risk	unable to assess
Other bias	Low risk	"This study was supported by the grants from Parke Davis & Co. Ltd., UK."

quotes are from the primary reference unless otherwise stated

* mmol/L converted to mg/dL using online converter

ACEI: angiotensin converting enzyme inhibitor

ARB: angiotensin receptor blocker

BMI: body mass index

CVD: cardiovascular disease

EF: ejection fraction

IQR: interquartile range

ITT: intention‐to‐treat

LV: left ventricular

LVEF: left ventricular ejection fraction

MRA: mineralocorticoid receptor antagonist

N: number of people

NCT: clinicaltrials.gov identifier

QoL: quality of life

RCT: randomised controlled trial

SD: standard deviation

TNF‐a: tumour necrosis factor‐alpha