DAPA-HF: Dapagliflozin is safe and efficacious in frail patients

Dapagliflozin added to guideline-recommended therapies was associated with a reduction of major cardiovascular events and all-cause death in patients with heart failure with reduced ejection fractions (HFrEF) irrespective of frailty status. Furthermore, the drug was well tolerated regardless of frailty status. These results may aid physicians who are reluctant to prescribe medications to frail patients.

“Heart failure (HF) and frailty often coexist,” said Dr Jawad Haider Butt (Copenhagen University Hospital, Denmark). Since frail patients may experience more adverse drug reactions, physicians are often reluctant to introduce new therapies to frail patients. The phase 3 DAPA-HF trial (NCT03036124) randomised 4,744 patients with New York Heart Association (NYHA) class II, III, or IV HF and an ejection fraction of ≤40% to placebo or dapagliflozin. In this population, dapagliflozin added to guideline-recommended therapies reduced the risk of major cardiovascular events and improved HF symptoms [1]. The current analysis assessed the efficacy and safety of dapagliflozin in patients with HFrEF from the DAPA-HF trial according to frailty status [2,3]. A 32-item frailty index (FI) was conducted, based on medical history, vital signs, lab data, and quality-of-life measures to stratify patients into not-frail (50.4%, FI ≤0.210), more-frail (33.9%, FI 0.211 to 0.310), and most-frail (15.7%, FI ≥0.311).

No interaction effect between frailty status and the efficacy of dapagliflozin was observed in the primary outcome, which was a composite of cardiovascular death and worsening HF (P_interaction=0.87). The corresponding hazard ratios were 0.72 in the not-frail group, 0.77 in the more-frail group, and 0.71 in the most-frail group. However, greater absolute reductions were reported in the most-frail group (-7.9 events per 100 person-years) compared with the more-frail group (-3.6) and the not-frail group (-3.5). Similar results were reported when frailty was assessed as a continuous variable (see Figure).

Figure: Treatment effect by frailty index [2]



Furthermore, the analysis revealed that quality-of-life was improved in all frailty groups after 8 months of dapagliflozin treatment, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) – Total Symptom Score, with frailer participants showing even significantly larger improvements on this outcome measure (P_interaction=0.001). Finally, frailty status did not significantly influence the rate of adverse event-driven treatment discontinuations of dapagliflozin compared with placebo (P_interaction=0.37), indicating that dapagliflozin was well tolerated regardless of frailty status.

Dr Butt concluded that dapagliflozin is safe and efficacious in patients with HFrEF, regardless of the level of frailty, informing clinicians on the applicability of this agent in frail patients.

1. McMurray JJV, et al. N Engl J Med. 2019;381(21):1995–2008.
2. Butt JH, et al. Efficacy and safety of dapagliflozin according to frailty in heart failure with reduced ejection fraction: a post hoc analysis of the DAP-HF trial. Young Investigator Award: Clinical Research, Heart Failure 2022, 21–24 May, Madrid, Spain.
3. Butt JH, et al. Ann Intern Med. 2022;175(6):820–830.

 

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Posted on 28 July 2022