Efficacy of SGLT2 Inhibitor Therapy in Middle Eastern Patients with Heart Failure

Abstract

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Contemporary management increasingly relies on disease-modifying pharmacotherapies, including angiotensin receptor–neprilysin inhibitors (ARNIs) and sodium–glucose cotransporter-2 (SGLT2) inhibitors, both now considered essential components of guideline-directed therapy. This study aimed to evaluate the real-world clinical impact of adding the SGLT2 inhibitor dapagliflozin to optimized medical therapy in a Middle Eastern population with chronic HFrEF.

In this multicenter, prospective, randomized trial, 400 ambulatory patients with NYHA class II–IV HF and left ventricular ejection fraction ≤40% were enrolled and assigned 1:1 to receive dapagliflozin (10 mg daily) or placebo, in addition to standard therapy consisting of ARNI/ACEi/ARB, beta-blockers, and mineralocorticoid receptor antagonists as tolerated. The primary endpoint was the time to first occurrence of cardiovascular (CV) death or HF hospitalization. Secondary outcomes included changes in NYHA class, six-minute walk distance (6MWD), and renal function at 12 months. Safety was closely monitored, and the study adhered to CONSORT guidelines.

The two groups were well matched at baseline, with a mean age of 62 ± 11 years, 65% male, and a mean LVEF of 32%. At 12 months, the composite endpoint occurred in 15% of dapagliflozin-treated patients versus 24% of placebo (hazard ratio 0.60; 95% CI 0.43–0.84; p<0.01), representing a 40% relative risk reduction. This benefit was mainly driven by fewer HF hospitalizations (10% vs 18%; p<0.01), while CV mortality trended lower (5% vs 8%; p=0.08). Functional outcomes improved significantly with dapagliflozin, including greater NYHA class improvement (45% vs 28%; p=0.02) and longer 6MWD gains (+35 m vs +10 m; p=0.03). Renal decline was attenuated (–2 vs –6 mL/min/1.73 m²; p=0.04). Adverse events, including hypotension and electrolyte disturbances, were similar across groups.

Dapagliflozin added to standard therapy reduced HF events and improved function in Middle Eastern HFrEF patients, supporting SGLT2 inhibitor use.