Pharmacotherapy for heart failure with reduced ejection fraction and health-related quality of life: a systematic review and meta-analysis

Aims The aim of this study was to synthesize the evidence on the effect of heart failure with reduced ejection fraction (HFrEF) pharmacotherapy on health-related quality of life (HRQoL). Methods and results We searched MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform in June 2020. Randomized placebo-controlled trials evaluating contemporary HFrEF pharmacotherapy and reporting HRQoL as an outcome were included. Two reviewers independently assessed studies for eligibility, extracted data, and assessed risk of bias and GRADE certainty of evidence. The primary outcome was HRQoL at last available follow-up analysed using a random-effects model. We included 37 studies from 5770 identified articles. Risk of bias was low in 10 trials and high/unclear in 27 trials. High certainty evidence from meta-analyses demonstrated improved HRQoL over placebo with sodium- glucose co-transporter 2 (SGLT2) inhibitors [standardized mean difference (SMD) 0.16, 95% confidence interval (CI) 0.08- 0.23] and intravenous iron (SMD 0.52, 95% CI 0.04- 1.00). Furthermore, high certainty evidence from >= 1 landmark trial further supported improved HRQoL with angiotensin receptor blockers (ARBs) (SMD 0.09, 95% CI 0.02- 0.17), ivabradine (SMD 0.14, 95% CI 0.04- 0.23), hydralazine-nitrate (SMD 0.24, 95% CI 0.04- 0.44) vs. placebo, and for angiotensin receptor-neprilysin inhibitor (ARNI) compared with an angiotensin-converting enzyme (ACE) inhibitor (SMD 0.09, 95% CI 0.02- 0.17). Findings were inconclusive for ACE inhibitors, beta-blockers, digoxin, and oral iron based on low-to-moderate certainty evidence. Conclusion ARBs, ARNIs, SGLT2 inhibitors, ivabradine, hydralazine- nitrate, and intravenous iron improved HRQoL in patients with HFrEF. These findings can be incorporated into discussions with patients to enable shared decision-making.