Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Discontinuation of treatment because of adverse effects
[108] RCT	3023 people with New York Heart Association (NYHA) functional class II to IV heart failure and left ventricular ejection fraction (LVEF) >40%	Proportion of people permanently discontinuing treatment caused by an adverse effect (hypotension, hyperkalaemia, and increase in plasma creatinine) or an abnormal laboratory value median follow-up of 36.6 months 270/1514 (18%) with candesartan 204/1509 (14%) with placebo	P = 0.001	Effect size not calculated	placebo
[109] RCT	4128 people with NYHA II to IV heart failure symptoms and LVEF 45% or greater	Proportion of people withdrawing because of an adverse effect mean follow-up of 49.5 months 331/2067 (16%) with irbesartan 288/2061 (14%) with placebo	P = 0.07		Not significant
Adverse effects
[109] RCT	4128 people with NYHA II to IV heart failure symptoms and LVEF 45% or greater	Proportion of people with hypotension mean follow-up of 49.5 months 60/2067 (2.9%) with irbesartan 62/2061 (3.0%) with placebo	P = 0.84		Not significant
[109] RCT	4128 people with NYHA II to IV heart failure symptoms and LVEF 45% or greater	Proportion of people with renal dysfunction mean follow-up of 49.5 months 69/2067 (3.3%) with irbesartan 57/2061 (2.8%) with placebo	P = 0.29		Not significant
[109] RCT	4128 people with NYHA II to IV heart failure symptoms and LVEF 45% or greater	Proportion of people with renal hyperkalaemia mean follow-up of 49.5 months 12/2067 (0.6%) with irbesartan 9/2061 (0.4%) with placebo	P = 0.34		Not significant
[110] RCT	850 people with NYHA functional class I to IV heart failure and LVEF >40%	Proportion of people with a serious adverse effect (including oedema and hypotension) 9/424 (2%) with perindopril 4 mg daily 4/426 (1%) with placebo	Significance not assessed