Short-term effects of combinations of heart failure therapies on blood pressure, kidney function and serum potassium

Among the most commonly cited reasons for failure to initiate comprehensive medical therapy in patients with heart failure are concerns relating to hypotension, kidney dysfunction and hyperkalemia. Here we performed a pooled individual participant-level analysis and developed a prediction model to estimate the short-term (2-12 weeks) treatment effects of combination medical therapy on systolic blood pressure (SBP), diastolic BP, estimated glomerular filtration rate (eGFR) and serum potassium. A total of 38,753 participants (16,877 with heart failure with reduced ejection fraction (HFrEF) and 21,876 with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF)) across nine randomized trials were included in the analysis, which tested angiotensin receptor blocker-neprilysin inhibitor (ARNI), steroidal mineralocorticoid receptor antagonist (sMRA), nonsteroidal MRA (nsMRA) and sodium glucose cotransporter-2 inhibitors (SGLT2i). For HFrEF, the estimated mean (95% prediction intervals (PIs)) treatment effect on SBP with combination ARNI + SGLT2i + sMRA therapy was -9.2 (-10.6 to -7.8) mmHg. For HFmrEF/HFpEF, the estimated mean (95% PI) treatment effects on SBP with SGLT2i + sMRA therapy and with SGLT2i + nsMRA therapy were -5.9 (-7.3, -4.6) and -4.8 (-5.7, -4.0) mmHg, respectively. For HFrEF, the estimated treatment effects of ARNI + SGLT2i + sMRA on eGFR and serum potassium were -6.8 (-7.9, -5.4) ml min