Genitourinary tract infections and SGLT2 inhibitors in heart failure: an EMPEROR-Pooled analysis

Abstract Background Sodium glucose co-transporter-2 inhibitors (SGLT2i) improve outcomes of patients with heart failure (HF). Urinary tract infections (UTI) are relatively common in HF, and their occurrence has been associated with an increased mortality risk. The use of SGLT2i has been associated with the occurrence of UTIs and mycotic genitourinary infections (MGI) which are a major cause of treatment discontinuation. Aims To study genitourinary infections in men and women with HF, their association with outcomes, and the impact of empagliflozin. Methods Analysis of EMPEROR-Pooled including a total of 9718 patients across the spectrum of ejection fraction. Descriptive statistics, Cox and time-varying survival models were used. The median follow-up time was 21 months. Results Throughout follow-up, 757 (7.8%) patients experienced a lower UTI, 60 (0.6%) MGI, and 41 pyelonephritis/urosepsis (0.4%). Genitourinary infections were more frequent in women than in men. Compared to patients without UTI/MGI, those with pyelonephritis/urosepsis were older and had higher comorbidity burden, whereas those with MGI were younger and had a higher prevalence of diabetes and obesity. Compared to placebo, empagliflozin was associated with a higher risk of lower UTI and MGI, particularly balanitis in men, but not pyelonephritis/urosepsis. The risk of death increased after UTI, but not after MGI. The effect of empagliflozin versus placebo on the composite of HF hospitalization or cardiovascular death was not modified by the occurrence of genitourinary infections. Conclusions Lower UTIs were relatively frequent in HF patients, whereas MGI and pyelonephritis/urosepsis were infrequent. SGLT2i increased the risk of lower UTI and MGI. Although UTI, but not MGI, were associated with a higher subsequent risk of death, the clinical benefits of SGLT2i were preserved regardless of genitourinary infection occurrence.