Duong Mai H, Gnjidic Danijela, McLachlan Andrew J, Redston Mitchell R, Goyal Parag, Mathieson Stephanie, Hilmer Sarah N
Kolling Institute, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, Sydney, NSW, Australia.
Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Br J Clin Pharmacol. 2025 Jan;91(1):23-37. doi: 10.1111/bcp.16223. Epub 2024 Sep 16.
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 I < 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.
本研究的目的是调查停用或降低心力衰竭（HF）药物治疗剂量的干预措施在老年人中是否可行以及是否存在风险。根据PRISMA 2020指南进行了系统评价和荟萃分析。从数据库建立至2023年3月8日对电子数据库进行检索。随机对照试验（RCT）和观察性研究纳入了年龄≥50岁、停用或降低HF药物治疗剂量的HF患者。结局指标为可行性（在随访时是否持续停用或降低HF药物治疗剂量）和相关风险（死亡率、住院率、药物撤药不良反应[ADWE]）。当异质性不显著（Higgins I²<70%）时，进行随机效应荟萃分析。按虚弱状态进行亚组分析。纳入了六项RCT（536名参与者）和27项观察性研究（810499名参与者），涉及六个治疗类别，随访时间为3 - 260周。RCT在稳定的慢性HF患者中进行。在慢性肾病患者中，降低肾素 - 血管紧张素系统抑制剂（RASI）剂量比继续使用的可能性高76%（风险比[RR] 1.76，95%置信区间[CI] 1.14 - 2.73），死亡率无差异（RR 0.64，95% CI 0.30 - 1.64）。与继续使用相比，在射血分数保留的情况下停用β受体阻滞剂是可行的（RR 1.00，95% CI 0.68 - 1.47）。参与者重新开始使用已停用利尿剂的可能性高25%（RR 0.75，95% CI 0.66 - 0.86）。与继续使用相比，停用洋地黄与住院风险增加5.5倍相关。HF恶化是最常见的ADWE。一项观察性研究测量了虚弱情况，但未按虚弱状态报告结局。对于≥75岁人群，降低或停用HF药物治疗剂量的适宜性及相关风险尚不确定。按虚弱状态评估结局有必要进行研究。
