Table 1.
Post-Hoc Analysis of Clinical Trials to Evaluate the Effect of Cardiovascular Drug Therapy by Frailty Levels
| Clinical Trial | Target Condition | Interventions | Primary Outcome | Frailty Tool | Treatment Effect HR (95% CI)a |
|---|---|---|---|---|---|
| HYVET (2015)[35] |
Hypertension | Indapamide ± perindopril vs placebo | Stroke | Deficit accumulation FI (60 deficits) |
Fit: 0.75 (0.40–1.38) Frail: 0.41 (0.10–1.65) |
| TRILOGY-ACS (2016)[41] |
ACS | Prasugrel vs clopidogrel | MACE | Physical frailty phenotype (self-report) |
Fit: 0.90 (0.77–1.06) Frail: 0.89 (0.54–1.46) |
| SPRINT (2016)[36] |
Hypertension | Intensive vs standard treatment | MACE | Deficit accumulation FI (37 deficits) |
Fit: 0.47 (0.13–1.39) Frail: 0.68 (0.45–1.01) |
| TOPCAT (2018)[37] |
HFpEF | Spironolactone vs placebo | CV death or HF admission | Deficit accumulation FI (39 deficits) |
No treatment effect heterogeneity by frailtyb |
| ENGAGE AF-TIMI 48 (2020)[38] |
AF | Edoxaban vs placebo | Stroke or systemic embolism | Deficit accumulation FI (40 deficits) |
Fit: 1.03 (0.71–1.49) Frail: 0.54 (0.20–1.50) |
| DAPA-HF (2022)[39] |
HFrEF | Dapagliflozin vs placebo | CV death or HF admission | Deficit accumulation FI (32 deficits) |
Fit: 0.72 (0.59–0.89) Frail: 0.71 (0.54–0.93) |
| DELIVER (2022)[40] |
HFrEF | Dapagliflozin vs placebo | CV death or HF admission | Deficit accumulation FI (30 deficits) |
Fit: 0.85 (0.68–1.06) Frail: 0.74 (0.61–0.91) |
Abbreviations: ACS, acute coronary syndrome; AF, atrial fibrillation; CI, confidence interval; CV, cardiovascular; FI, frailty index; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio; MACE, major adverse cardiovascular events.
a
Treatment effects for the fittest group and the frailest group are shown. None of the clinical trials found statistically significant heterogeneity in treatment effect by frailty levels.
b
Quantitative results were not reported by frailty levels.