DAPA-HF: Dapagliflozin 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 and 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 [1].

“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 DAPA-HF trial (NCT03036124) randomised 4,744 patients with HF and an ejection fraction of ≤40% to placebo or dapagliflozin [2]. In this population, dapagliflozin added to guideline-recommended therapies reduced the risk of major cardiovascular events and improved HF symptoms. The current analysis assessed the efficacy and safety of dapagliflozin in patients with HFrEF from the DAPA-HF trial according to frailty status. 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%), more frail (33.9%), and most frail (15.7%).

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 frailest group. However, greater absolute reductions were reported in the frailest group (-7.9 events per 100 person-years) compared with the more-frail group (-3.6) and the not-frail group (-3.5).

Furthermore, the analysis revealed that quality of life improvements after 8 months of dapagliflozin treatment, as assessed by the Kansas City Cardiomyopathy Questionnaire – Total Symptom Score, were present in all frailty groups, but that frailer patients had 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 Haider 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. 
   
   1. Haider Butt J, et al. The dapagliflozin and prevention of adverse outcomes in heart failure trial (DAPA-HF): Results according to frailty status. Young investigator award clinical research, Heart Failure 2022, 21–24 May, Madrid, Spain.
   
   
   2. McMurray JJV, et al. N Engl J Med 2019;381:1995–2008.

 

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Posted on 23 May, 202213 June, 2022