- Design
- Systematic review and meta-analysis
- Population
- 34 studies, 92,916 patients aged ≥65 with HFrEF
- Primary outcome
- All-cause mortality with vs without GDMT
- Effect
- HR 0.69 (95% CI 0.64 to 0.74); frail patients less likely treated RR 0.63
This meta-analysis, published 24 September in Heart, pooled 34 studies of 92,916 patients aged 65 and over with heart failure and reduced ejection fraction from 1994 to 2024, comparing those who did and did not receive guideline-directed medical therapy.
Guideline therapy was associated with lower mortality (HR 0.69, 95% CI 0.64 to 0.74; I² 71%). Hypotension, acute kidney injury and hypoglycaemia were not more common. Beta-blockers were associated with more bradycardia (RR 3.98). Frail patients were less likely to receive therapy (RR 0.63). No study reported outcomes with all four drug classes, and most GDMT groups received only one or two.
Older patients, and frail ones in particular, are often left on partial or no guideline therapy for fear of side effects. These data suggest the survival benefit holds after 65 and that the feared harms were not borne out, apart from bradycardia with beta-blockers. Frailty is a reason to titrate slowly and monitor, not to withhold.
- Offer guideline heart failure therapy to older patients with reduced ejection fraction, including the frail.
- Start low and titrate slowly, checking pulse, blood pressure and renal function.
- Watch for bradycardia on beta-blockers, which was about four times more common.
- Review every older HFrEF patient for drug classes they have never been offered.
Why it matters
Challenges therapeutic nihilism in older and frail patients with heart failure.
Don't overread it
Mostly observational data with one or two drug classes; it cannot show the benefit of full four-drug therapy in the very old.
The statistics, in plain English
A hazard ratio of 0.69 means about 31% lower risk of death. The studies are observational and heterogeneous (I² 71%), so healthier patients being treated more often may inflate the benefit.
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