Blockade of the neurohormonal systems in heart failure with preserved ejection fraction: A contemporary meta-analysis

Background: Although individual studies failed to demonstrate significant benefits with neurohormonal inhibitors in patients affected by heart failure (HF) with preserved ejection fraction (HFpEF), an evident trend towards a reduction in hospitalization and mortality has been previously documented in most cases. We aimed to conduct an updated meta-analysis on the effect of neurohormonal inhibitors [renin-angiotensin-aldosterone system (RAAS) inhibitors and angiotensin receptor neprilysin inhibitors (ARNi)] on the primary composite outcome of mortality and hospitalizations for HF and on the secondary outcomes of mortality and hospitalizations separately analyzed.

Methods and results: The extended literature search ended up with the identification of a total of 12 studies cumulatively including 30,882 patients, 16,540 in the treatment and 14,432 in the control groups. Eleven studies explored the outcome of death, 9 studies reported data about HF hospitalizations and 8 studies explored the composite outcome of death and HF hospitalizations. Our meta-analysis showed that treatment with neurohormonal inhibitors was significantly associated with a reduced risk of the primary composite outcome (OR 0.87, 95%CI: 0.82-0.93, p < .001; I² = 2.2.) and with a decreased risk of HF hospitalizations (OR 0.84, 95%CI: 0.75-0.94, p = .002; I² = 63%). In contrast, no significant effect on death was found (OR 0.79, 95%CI: 0.55-1.12, p = .184; I² = 96.4%). Results remained substantially unchanged in the leave-one-out sensitivity analysis.

Conclusion: Our current work supports a beneficial effect of neurohormonal inhibitors (RAAS blockers and ARNi) on the primary composite outcome of death and HF hospitalizations and on the secondary outcome of HF hospitalizations in HFpEF patients. This finding provides support to the current prevalent clinical approach and to level of evidence reported in the Guidelines.