Influence of chronic obstructive pulmonary disease on cardiovascular outcomes and mortality benefits of sodium glucose co-transporter inhibitors in heart failure patients: A systematic review and meta-analysis

BACKGROUND By 2030, healthcare expenditures related to congestive heart failure (CHF) in the United States are projected to surpass 70 billion. Despite substantial advances in guideline-directed medical therapy, morbidity and mortality remain unacceptably high, particularly among patients with concomitant chronic obstructive pulmonary disease (COPD), a comorbidity reported in approximately 5%-41% of individuals with CHF. Although COPD is independently associated with worse CHF outcomes, its influence on the mortality benefit conferred by sodium-glucose cotransporter-2 (SGLT-2) inhibitors remains poorly defined. OBJECTIVE To evaluate whether COPD alters the cardiovascular and mortality benefit of SGLT-2 inhibitors in CHF patients. METHODS PubMed, Cochrane and Google Scholar were searched from inception to February 2025 to identify studies meeting inclusion criteria. Review Manager was employed to calculate results in the form of relative risk (RR) with 95% confidence interval. RESULTS Our analysis of 15, 058 patients (1, 725 (11%) COPD patients) showed that COPD was associated with significantly higher risks of composite outcomes (RR=1. 63; 95% CI: 1. 49-1. 79; p<0. 00001), CV mortality (RR=1. 62; 95% CI: 1. 39-1. 88; p<0. 0001), heart failure hospitalization (RR=1. 84; 95% CI: 1. 40-2. 40; p<0. 00001), and all-cause mortality (RR=1. 59; 95% CI: 1. 42-1. 78; p<0. 00001). Additionally, adverse outcomes were more frequent in COPD patients, including volume depletion (RR=1. 34; 95% CI: 1. 25-1. 51; p<0. 00001), and adverse renal events (RR=1. 46, 95% CI: 1. 17-1. 82; P=0. 0007). CONCLUSION Our analysis indicates that heart failure (HF) patients with COPD may drive a somewhat attenuated benefit from SGLT-2 inhibitors, underscoring a clinical profile that merits careful consideration.