The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: A systematic review and meta-analysis

Abstract

The aim of this study was to investigate whether interventions to discontinue or down-titrate heart failure (HF) pharmacotherapy are feasible and associated with risks in older people. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to 8 March 2023. Randomized controlled trials (RCTs) and observational studies included people with HF, aged ≥50 years and who discontinued or down-titrated HF pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalization, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I² < 70%). Sub-analysis by frailty status was conducted. Six RCTs (536 participants) and 27 observational studies (810 499 participants) across six therapeutic classes were included, for 3–260 weeks follow-up. RCTs were conducted in patients presenting with stable chronic HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% more likely than continuation (risk ratio [RR] 1.76, 95% confidence interval [CI] 1.14–2.73), with no difference in mortality (RR 0.64, 95% CI 0.30–1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95% CI 0.68–1.47). Participants were 25% more likely to re-initiate discontinued diuretics (RR 0.75, 95% CI 0.66–0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalization compared to continuation. Worsening HF was the most common ADWE. One observational study measured frailty but did not report outcomes by frailty status. The appropriateness and associated risks of down-titrating or discontinuing HF pharmacotherapy in people aged ≥75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.