Table 2.

Studies evaluating the efficacy of drug therapy in the management of elderly and frail heart failure patients

Study, author	Drug	Study description	Age cut‐off/frailty assessment tool	HFrEF proportion (%)	HFpEF proportion (%)	N	Results
Ahmed 2007 74	Digoxin	A post hoc analysis of the DIG trial in elderly patients aged ≥65 years to evaluate the efficacy of digoxin at high or low serum digoxin levels	Age ≥65	87	13	5548	‐ Reduction in all‐cause mortality, all‐cause hospitalizations and HF hospitalizations in patients with low serum digoxin concentration (0.5–0.9 ng/mL); only reduction in HF hospitalizations with high serum digoxin concentration (≥1 ng/mL)
Hernandez 2009 75	Beta‐blocker	A retrospective analysis from the OPTIMIZE registry to assess long‐term outcomes in patients aged ≥65 years newly initiated on beta‐blocker therapy	Age ≥65	42	58	24 689	‐ Reduction in all‐cause hospitalizations and mortality compared to those not treated with beta‐blockers
Yaku 2019 76	MRA	A propensity‐matched analysis from the Kyoto Heart Failure registry evaluating use of MRAs in elderly patients (median age 80) recently hospitalized for HF	Elderly, median age 80	36	64	3717	‐ Reduction in the composite endpoint of HF hospitalizations and mortality in the overall cohort ‐ Subgroup analysis of patients with EF ≤ 40% did not have significant reduction in the primary endpoint
Dewan 2020 5	ARNI and renin inhibitor	A combined analysis from the PARADIGM and ATMOSPHERE trials in patients stratified by severity to frailty to evaluate the efficacy and safety of ARNI and aliskiren	Rockwood cumulative deficit index	100	0	13 265	‐ No interaction between ARNI and all‐cause death, cardiovascular death or first HF hospitalization across the frailty groups
Greene 2021 77	ARNI	A retrospective analysis from the Get With the Guidelines—Heart Failure registry evaluating outcomes in hospitalized patients aged ≥65 years with ARNI	Age ≥65	100	0	14 230	‐ Compared to ACEi/ARB, there was a reduced risk of all‐cause mortality in patients receiving ARNI ‐ Compared to patients not on ARNI, there was a reduced risk of all‐cause mortality and hospitalizations in patients receiving ARNI
Butt 2022 78	SGLT‐2 inhibitor	A post hoc analysis of DAPA‐HF in elderly patients aged ≥65 years with HFrEF to evaluate the efficacy and safety of dapagliflozin	Age ≥65	100	0	4742	‐ Reduction in worsening HF and cardiovascular death across all frailty subgroups stratified by frailty index
Butt 2022 79	SGLT‐2 inhibitor	A post hoc analysis of DELIVER in patients stratified by severity of frailty to evaluate the efficacy and safety of dapagliflozin	Rockwood cumulative deficit index	0	100	6258	‐ Improvement in KCCQ‐CSS in patients with higher frailty indices ‐ Similar reduction in primary endpoint events across the spectrum of frailty
Butt 2022 15	ARNI	A post hoc analysis of PARAGON‐HF in patients stratified by severity of frailty to evaluate the efficacy and safety of dapagliflozin	Rockwood cumulative deficit index	0	100	4795	‐ Significant reduction in primary endpoint events of HF hospitalization and cardiovascular death when frailty examined as a continuous measure

Abbreviations: ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor–neprilysin inhibitor; DAPA‐HF, Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; DIG, Digitalis Investigation Group; EF, ejection fraction; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; KCCQ‐CSS, Kansas City Cardiomyopathy Questionnaire—Clinical Summary Score; MRAs, mineralocorticoid receptor antagonists; OPTIMIZE, Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure; SGLT‐2, sodium–glucose co‐transporter 2.