3 Key Takeaways
Plain English Summary- 01Core Finding
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).
- 02Study Evidence
Tested in a randomized controlled trial (38,753 participants) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
For HFrEF, the estimated treatment effects of ARNI + SGLT2i + sMRA on eGFR and serum potassium were -6.8 (-7.9, -5.4) ml min -1 m -2 and +0.30 (0.25, 0.35) mmol l -1 , respectively. For HFmrEF/HFpEF, the treatment effects for combination SGLT2i + sMRA and SGLT2i + nsMRA on eGFR were -7.7 (-8.9, -6.4) and -6.1 (-6.7, -5.5) ml min -1 m -2 , respectively and for serum potassium were +0.34 (0.29, 0.38) and +0.21 (0.18, 0.25) mmol l -1 , respectively.
These analyses provide individualized estimates of the expected treatment effect for any combination of medical therapies in HFrEF and HFmrEF/HFpEF on BP, kidney function and serum potassium.
The Discovery
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.
How It Works, Simply
This nephrology research focuses on receptor targeting. Researchers evaluated it using a randomized controlled trial (38,753 participants) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
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).
- 02Study Evidence
Tested in a randomized controlled trial (38,753 participants) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (38,753 participants) · Randomized Clinical Trial
Biological Pathway & Modality
Receptor targeting
Intervention: Short-term effects of combinations of heart failure therapies on blood pressure
Experimental Findings & Endpoints
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.
Clinical Translation & Practice Context
For HFrEF, the estimated treatment effects of ARNI + SGLT2i + sMRA on eGFR and serum potassium were -6.8 (-7.9, -5.4) ml min -1 m -2 and +0.30 (0.25, 0.35) mmol l -1 , respectively.
For HFmrEF/HFpEF, the treatment effects for combination SGLT2i + sMRA and SGLT2i + nsMRA on eGFR were -7.7 (-8.9, -6.4) and -6.1 (-6.7, -5.5) ml min -1 m -2 , respectively and for serum potassium were +0.34 (0.29, 0.38) and +0.21 (0.18, 0.25) mmol l -1 , respectively.
These analyses provide individualized estimates of the expected treatment effect for any combination of medical therapies in HFrEF and HFmrEF/HFpEF on BP, kidney function and serum potassium.
The Bottom Line · Clinical Pearl
“These analyses provide individualized estimates of the expected treatment effect for any combination of medical therapies in HFrEF and HFmrEF/HFpEF on BP, kidney function and serum potassium.”
Published in Nature Medicine · Current Stage: Randomized Clinical Trial