Investigating Adverse Drug Events and Adverse Drug Withdrawal Effects Associated with Heart Failure Pharmacotherapy in Older People Living with Frailty

Abstract

Background

Frailty is common among older people with heart failure (HF). Optimising HF medications can improve clinical outcomes, but efficacy and safety are uncertain for older people with frailty.

Aim

To explore the prevalence and management of adverse drug events (ADEs) and adverse drug withdrawal effects (ADWEs) associated with optimising and deprescribing HF medications for older people with frailty.

Methods

Participants: Older adults with HF diagnosis on HF medications and doctors, nurses and pharmacists. Design: Systematic reviews and meta-analysis (Study 1, 2); a multi-hospital cross-sectional study (Study 3); and a qualitative study in primary care and hospital (Study 4).

Results

Study 1: Of 2,416 studies, three observational studies of people >65 years with objective frailty reported ADEs. Frail people on renin-angiotensin system inhibitors (RASIs) had a 2-fold risk of mortality, and digoxin probably caused falls, tiredness and nausea. Study 2: Of 5,461 studies, six randomised controlled trials and 27 observational studies reported deprescribing of HF medications in HF patients >50 years. Four studies reported outcomes for people >75 years. No studies reported outcomes by frailty status. Worsening HF was the most common ADWE. Study 3: Of 439 (22%) inpatients >75 years with unspecified HF, 305 (69.5%) had frailty risk. Diuretic use was common with RASI (n=67, 16%) or beta-blockers (n=62, 15%). Increasing frailty risk showed a higher prevalence of ADEs (31-84%), falls (12-46%), and delirium (8- 49%). Study 4: Interviews and focus groups with consumers (n=4) and healthcare professionals (n=28) identified three main themes: individual factors, medications and access to healthcare. A conceptual model describes the interplay between frailty, ADEs, and ADWEs of HF medications on quality of life in older people, which needs further development.

Conclusion

Future research of HF medications in older people may report objective frailty and HF phenotypes.