Background: Heart failure (HF) with pulmonary hypertension due to left-sided heart disease (PH-LHD) is associated with poor prognosis. Dapagliflozin showed benefits in terms of ejection fraction (EF); meanwhile, sildenafil improved pulmonary pressures and right ventricular function in PH -LHD in recent clinical studies. This study assesses the potential additive effects of dapagliflozin and sildenafil on cardiac function and pulmonary hemodynamics in this population. Methods: In this prospective, randomized, controlled trial, 93 participating patients with HF and PH-LHD were randomly assigned to receive dapagliflozin (control group, n = 48) or dapagliflozin plus sildenafil 25 mg/day (test group, n = 45) in addition to conventional therapy for HF for 12 weeks. The primary outcomes were assessing changes in echocardiographic hemodynamic parameters. Secondary outcomes included outcomes, changes in cardiac enzyme (troponin), kidney function (serum creatinine), and lipid profile. Results: The average baseline median left ventricular ejection fraction (LVEF) for both groups was 30%, and the Pulmonary Artery Systolic Pressure (PASP) median was 50 mmHg. At follow-up, PASP had declined, and EF had improved compared to baseline. However, there were no statistically noticeable variations between the groups (p = 0.458, 0.331, respectively). No notable changes were observed in secondary and safety outcomes, including hospitalization rate, number of deaths, kidney function, and cardiac enzymes (p = 0.524, 1, 0.923, and 0.574, respectively). Conclusions: Addition of sildenafil to dapagliflozin did not demonstrate any significant clinical or hemodynamic benefit over dapagliflozin monotherapy in HF patients and PH-LHD. Further studies are warranted to evaluate the effects over the long term.
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