Angiotensin-neprilysin inhibition in acute decompensated heart failure: a meta-analysis of randomized controlled trials

Angiotensin receptor – neprilysin inhibitors (ARNI) are well-established for chronic heart failure (HF) with reduced ejection fraction. However, their efficacy and safety after stabilization of acute decompensation (ADHF) remain unclear. This meta-analysis evaluates ARNI versus angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) post-ADHF. Meta-analysis of randomized controlled trials (RCTs) from PubMed, Scopus, WOS, Embase, and CENTRAL up to November 2024. Risk ratios (RR) and standardized mean differences (SMD) with 95% confidence intervals (CI) were used. Three RCTs (1,741 patients) were included. ARNI use after ADHF stabilization significantly reduced HF rehospitalization/all-cause mortality (RR: 0.71; 95% CI: 0.57–0.88; <i>p</i> &lt; 0.01), HF rehospitalization (RR: 0.73; 95% CI: 0.57–0.93; <i>p</i> = 0.01), worsening renal function (RR: 0.80; 95% CI: 0.64–1.00; <i>p</i> = 0.048), and NT-proBNP at 4 weeks (SMD: −0.24; 95% CI: −0.34 to −0.14; <i>p</i> &lt; 0.0001) and 8 weeks (SMD: −0.21; 95% CI: −0.31 to −0.10; <i>p</i> = 0.0001). However, ARNI increased symptomatic hypotension risk (RR: 1.33; 95% CI: 1.04–1.71; <i>p</i> = 0.024). initiation of ARNI after ADHF stabilization is more effective than ACEIs/ARBs for cardiovascular and renal outcomes, albeit with higher symptomatic hypotension risk. PROSPERO: CRD42024618027. Heart failure is a condition where the heart cannot pump blood effectively. Sometimes, symptoms suddenly get worse, leading to hospital admission. This is called acute decompensated heart failure (ADHF). After recovery, patients are given medications to prevent future episodes. A newer treatment called angiotensin receptor – neprilysin inhibitor (ARNI) has shown benefits in long-term heart failure, but its use right after ADHF hasn’t been fully studied. We reviewed data from three high-quality studies involving 1,741 patients who had recently been treated for ADHF. We compared those given ARNI to those given older treatments called ACEIs or ARBs. Patients who received ARNI were less likely to return to the hospital or die from any cause. They also showed better results on a heart failure blood test and had fewer kidney problems. However, ARNI were more likely to cause low blood pressure that led to symptoms like dizziness. In summary, ARNI seem to offer more benefits than older medications when started after an ADHF episode. But they can also cause more side effects related to blood pressure. Doctors should consider both the benefits and risks when choosing treatment.