DAPA-HF also showed benefit regardless of baseline QoL
PHILADELPHIA – Heart failure with reduced ejection fraction appears to respond to dapagliflozin (Farxiga) similarly across age groups and regardless of baseline quality of life, researchers reported here in two analyses of the DAPA-HF trial.
Both studies were presented as late-breaking clinical trials at the annual scientific sessions of the American Heart Association and published online at the time of presentation in Circulation.
In commenting on the studies as discussant at the session, Carolyn Lam, MBBS, PhD, of the National Heart Centre Singapore, suggested that dapagliflozin could become – if confirmatory studies show the same results -- one of the pillars of therapy to reduce mortality in heart failure patients with reduced ejection fraction.
"Dapagliflozin meets the three critical goals of heart failure with reduced ejection fraction management: patients die less, are hospitalized less, and feel better – regardless of age, regardless of diabetes status," she said.
Analysis by Age
"Dapagliflozin reduced the risk of worsening heart failure events and cardiovascular death and improved symptoms, in patients with heart failure with reduced ejection fractions, when added to standard therapy," reported Felipe Martinez, MD, of Cordoba National University in Argentina. "These benefits were consistent across the range of ages studied."
In patients less than age 55, there was a 13% decrease in the risk of experiencing the primary composite endpoint of cardiovascular death, heart failure hospitalization, and urgent heart failure visits – but that difference was not statistically significant (HR 0.87, 95% CI 0.60-1.28).
However, in the age group of patients ages 55-64, there was a 29% reduction that did reach statistical significance (HR 0.71, 95% CI 0.55-0.93).
In the age group of patients 65-74 years, there was a 24% reduction (HR 0.76, 95% CI 0.61-0.95), and in the oldest group of patients, ages 75 or older, there was a 32% reduction in risk of experiencing the primary endpoint (HR 0.68 [95% CI 0.53-0.88]), Martinez said.
The overall study enrolled 2,371 patients who were assigned to placebo on top of standard therapy and 2,373 patients who were assigned to receive dapagliflozin (10 mg). There were 296 patients on placebo and 340 patients were assigned to dapagliflozin who were less than age 55; there were 558 patients on placebo and 591 on dapagliflozin who were age 75 or older, the researchers reported.
"Dapagliflozin offers a new approach to the treatment of heart failure with reduced ejection fraction, irrespective of age," Martinez said.
Analysis by Quality of Life
In a companion analysis of DAPA-HF, treatment with dapagliflozin improved outcomes at every tertile of quality of life scoring on the Kansas City Cardiomyopathy Questionnaire (KCCQ).
"Dapagliflozin improved all key clinical outcomes, including cardiovascular death and worsening heart failure, to a similar extent across the entire range of the KCCQ at baseline," Mikhail Kosiborod, MD, of St. Luke's Mid-America Heart Institute in Kansas City, Missouri, reported at the late-breaking trial session.
Patients at the lowest baseline tertile with KCCQ scores of 65.6 or less (out of a possible 100, at best) had a 30% lower risk of a primary composite endpoint event if treated with dapagliflozin versus placebo (HR 0.70, 95% CI 0.57-0.86).
In the middle tertile with scores of 65.7-87.5 on the KCCQ, dapagliflozin reduced the risk of experiencing the primary endpoint by 23% (HR 0.77, 95% CI 0.61-0.98).
In the tertile with the best quality of life, based on KCCQ scores greater than 87.5, there was a 38% reduction in experiencing the endpoint with dapagliflozin (HR 0.62, 95% CI 0.46-0.83).
"Dapagliflozin offers a new approach to improving symptoms, functional limitations, and quality of life in patients with heart failure with reduced ejection fraction," Kosiborod said in his late-breaker study.
The study was supported by AstraZeneca.
Lam disclosed relevant relationships with Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Boston Scientific, Novartis, Amgen, Merck, Janssen Research & Development, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, Jana Care, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global, Radcliffe Group, and Corpus.
Kosiborod disclosed relevant relationships with AstraZeneca, Boehringer Ingelheim, Sanofi, Amgen, Novo Nordisk, Merck (Diabetes), Eisai, Janssen, Bayer, GlaxoSmithKline, Glytec, Intarcia, Novartis, Applied Therapeutics, Amarin, and Eli Lilly.
Martinez disclosed relevant relationships with AstraZeneca.
Source Reference: McMurray J, et al "Efficacy and safety of dapagliflozin in HFrEF according to age: insights from DAPA-HF" Circulation, November 17, 2019.
Source Reference: Kosiborod M, et al "Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF Trial" Circulation, August 17, 2019.
Read the original article on Medpage Today: Age No Deterrent to Dapagliflozin in HF