Dapagliflozin safe, effective in HF patients across global regions

Dapagliflozin for individuals with heart failure (HF) demonstrates consistent safety and efficacy across regions worldwide despite geographic differences in patient characteristics, background treatment, and event rates, reports a recent study.

These findings reinforce “the consistency of benefit of this class of treatment across all subgroups examined to date and [highlight] the potential value to the estimated 64 million patients living with HF worldwide,” the researchers said. [Lancet 2018;392:1789-1858; Cardiovasc Res 2023;118:3272-3287]

A patient-level pooled analysis was conducted on the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trials, which assessed the effects of dapagliflozin in HF with reduced ejection fraction (HFrEF) and HF with mildly reduced ejection fraction (HFmrEF)/HF with preserved ejection fraction (HFpEF), respectively.

A total of 11,007 patients were included in the analysis, of whom 5,159 (46.9 percent) were in Europe, 1,528 (13.9 percent) in North America, 1,998 (18.2 percent) in South America, and 2,322 (21.1 percent) in Asia. [J Am Coll Cardiol 2023;82:1014-1026]

A higher rate of the composite of worsening HF or cardiovascular death, the primary outcome, was observed in North America (13.9, 95 percent confidence interval [CI], 12.5‒15.4) than in other regions, namely Europe (10.8, 95 percent CI, 10.1‒11.5), South America (10.0, 95 percent CI, 9.0‒11.1), and Asia (10.5, 95 percent CI< 9.5‒11.5).

The benefit of dapagliflozin on the primary outcome did not differ by region: dapagliflozin vs placebo (Europe: hazard ratio [HR], 0.85, 95 percent CI, 0.75‒0.96; North America: HR, 0.75, 95 percent CI, 0.61‒0.93; South America: HR, 0.72, 95 percent CI, 0.58‒0.89; Asia: HR, 0.74, 95 percent CI, 0.61‒0.91; p_interaction=0.40). This finding persisted when evaluated separately for HFrEF (p_interaction=0.39) and HFmrEF/HFpEF (p_interaction=0.84).

Notably, patients in North America were more likely to discontinue randomized treatment than did those in other regions (placebo discontinuation: 21.8 percent in North America vs 6.4 percent in South America). However, discontinuation rates between dapagliflozin and placebo did not differ by region.

These findings support those of the other most recent studies involving ambulant patients with chronic HF, according to the researchers.

“In particular, we found similar regional variations in age (younger patients in Asia and South America), NYHA functional class (better among patients in Asia and South America), systolic blood pressure (higher in Europe and lower in North America and Asia), atrial fibrillation (less prevalent in South America and Asia), and treatment (higher use of sacubitril/valsartan and implanted cardiac devices in North America and Europe but a persistently low rate of use of mineralocorticoid receptor antagonists in North America compared with the rest of the world),” they said. [Eur Heart J 2016;37:3167-3174; Circ Heart Fail 2021;14:e007901; Eur Heart J 2021;42:4442-4451; Eur J Heart Fail 2019;21:577-587]

“Further efforts are needed to assure equitable access to SGLT2 inhibitor therapy for patients with HF around the world,” the researchers said.