Effect of dapagliflozin in patients in Asia with heart failure with mildly reduced or preserved ejection fraction: insights from DELIVER
Authors: Wang X , Lam C S P , Claggett B , Miao M , Shah S J , Jhund P S , Desai A S , Chiang C , Pham V N , Han Y , Kitakaze M , Langkilde A M , Mcmurray J J V , Solomon S D , Vaduganathan M 
Published: November 2023

Abstract

Background
A large and growing fraction of the global heart failure (HF) population lives in Asia. One-fifth of participants in the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial were enrolled from Asia, providing a rich source of contemporary data to understand their unique clinical profiles and responses to sodium-glucose cotransporter 2 (SGLT2) inhibition.

Purpose
To assess the differences in clinical characteristics, outcomes, and response to dapagliflozin in patients from Asia vs outside Asia among patients with HF with mildly reduced or preserved ejection fraction in the DELIVER trial.

Methods
DELIVER was a global randomized clinical trial enrolling across 353 sites in 20 countries. Baseline clinical characteristics from patients enrolled in DELIVER trial were compared between patients in Asia vs outside Asia. The primary outcome was a composite of worsening HF or cardiovascular (CV) death. The effect of dapagliflozin on primary and secondary outcomes were compared in patients in Asia vs outside Asia.

Results
Among 6,263 participants in the DELIVER trial, 1,226 (19.6%) were enrolled in Asia (310 in China, 422 in Japan, and 318 in Taiwan, and 176 in Vietnam). Compared to patients outside Asia, participants from Asia were similar in age, more likely to be men with previous HF hospitalization, less likely to have obesity, diabetes, hypertension, or history of myocardial infarction, and had lower symptom burden despite similar natriuretic peptide levels (Figure 1). After adjusting for age, sex, and baseline LVEF, those in Asia faced similar risks of HF events but lower risk of mortality compared with those enrolled outside Asia (all-cause mortality Asia vs. outside Asia: HR 0.60, 95% confidence interval [CI] 0.49 – 0.72, Table 1). Within Asia, all-cause mortality was highest in Vietnam (6.8 per 100 person-year [py]), followed by Taiwan (6.7 per 100 py), Japan (3.5 per 100 py) and China (3.3 per 100 py).
Dapagliflozin reduced the primary outcome in participants enrolled in Asia (hazard ratio [HR] 0.89, 95% CI 0.67-1.18) and outside Asia (HR 0.80, 95% CI 0.71 – 0.92) to a similar extend (P-interaction = 0.54, Figure 1). Similarly, region did not modify the treatment effect of dapagliflozin on CV death, HF hospitalization, all-cause death, CV death and recurrent HF events, or changes in Kansas City Cardiomyopathy Questionnaire scores (P-interaction &gt; 0.30 for all). Serious adverse events and rates of drug discontinuation were also balanced in both treatment arms, irrespective of enrollment in Asia vs. outside Asia.

Conclusions
In the global DELIVER trial, dapagliflozin reduced the risk of CV death or HF events and was well tolerated both among participants enrolled in Asia and other geographic regions.Figure 1Table 1