Dapagliflozin Has Similar Efficacy for Heart Failure Globally

Dapagliflozin has consistent efficacy and safety in patients with heart failure (HF) in different global regions even when patient characteristics, background treatment, and outcomes vary considerably, according to a study in the Journal of the American College of Cardiology.

Researchers sought to determine whether the efficacy and safety of dapagliflozin in HF were consistent across geographic regions using data from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) randomized placebo-controlled trials.

Both trials enrolled patients diagnosed with HF who had New York Heart Association functional class II to IV and increased natriuretic peptide levels. Patients with a left ventricular ejection fraction (LVEF) of 40% or less were randomized in DAPA-HF, and those with an LVEF of more than 40% were randomized in DELIVER.

Patients were enrolled in 20 countries in each trial and were classified into 4 geographic regions: Europe, North America, South America, and Asia. The primary outcome in the 2 trials was the composite of worsening HF or death of cardiovascular causes.

The pooled data set included 11,007 patients, of whom 5503 were assigned to placebo and 5504 to dapagliflozin. Of the cohort, 46.9% were enrolled in Europe, 13.9% in North America, 18.2% in South America, and 21.1% in Asia. Asian patients were younger (mean age, 67.6 years) than those in South America (mean age, 68.3 years), Europe (mean age, 70.0 years), and North America (mean age, 71.2 years).

Patient outcomes varied by geographic region, but the efficacy of dapagliflozin did not vary. The primary outcome rate according to geographic regions was greater in North America (13.9; 95% CI, 12.5-15.4) compared with Europe 10.8 (95% CI, 10.1-11.5), Asia 10.5 (95% CI, 9.5-11.5), and South America 10.0 (95% CI, 9.0-11.1).

North America had the highest rate of worsening HF events and rates of total HF hospitalizations. South America had the highest rate of unadjusted and adjusted cardiovascular and all-cause mortality, and Asia had the lowest rates.

The hazard ratio for dapagliflozin vs placebo for the primary endpoint was 0.85 (95% CI, 0.75-0.96) in Europe, 0.75 (95% CI, 0.61-0.93) in North America, 0.72 (95% CI, 0.58-0.89) in South America, and 0.74 (95% CI, 0.61-0.91) in Asia (P _interaction =.40). For LVEF of 40% or less the P_interaction was .39, and for LVEF of greater than 40% the P_interaction was .84. The effect of dapagliflozin was consistent regardless of LVEF in each region.

North American patients were most likely, and South American patients least likely, to discontinue randomized treatment for any reason (placebo group, 21.8% in North America vs 6.4% in South America). Patients receiving placebo and dapagliflozin had similar safety profiles in each region.

Among several study limitations, the participants were selected according to specific trial inclusion and exclusion criteria, and the results may not be generalizable to all patients with HF. In addition, patients were unavailable from Africa, and the analysis cannot account for many potential influences on outcomes, including climate and other environmental factors, diet, and lifestyle.

“Further efforts are needed to assure equitable access to sodium-glucose cotransporter-2 inhibitor therapy for patients with HF around the world,” wrote the investigators.

Disclosure: The DAPA-HF and DELIVER trials were funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.