Efficacy and safety of sacubitril valsartan in heart failure compared to renin angiotensin adosterone system inhibitors: a systematic review and meta analysis of randomised controlled trials

Introduction: Heart failure (HF) is still a major cause of morbidity and mortali-ty all over the world. Aim of the study was to assess the benefits and harms of sacubitril/valsartan (S/V) compared to angiotensin-converting enzyme inhibi-tors (ACEI) or angiotensin receptor blockers (ARB) in patients with HF.Material and methods: We systematically searched for randomised con-trolled trials (RCTs) evaluating S/V vs. ACEI or ARB in acute or chronic HF in August 2021. Primary outcomes were HF hospitalisations and cardiovas-cular (CV) mortality; secondary outcomes included all-cause mortality, bio-markers, and renal function.Results: We selected 11 RCTs (n = 18766) with 2-48 months follow-up. Five RCTs had ACEIs as control, 5 RCTs had ARBs as control, and one RCT had both ACEI and ARB as control. Compared to ACEI or ARB, S/V reduced HF hos-pitalisations by 20% (HR = 0.80, 95% CI: 0.68-0.94; 3 RCTs; I2 = 65%; high CoE), CV mortality by 14% (HR = 0.86, 95% CI: 0.73-1.01; 2 RCTs; I2 = 57%; high CoE), and all-cause mortality by 11% (HR = 0.89, 95% CI: 0.78-1.00; 3 RCTs; I2 = 36%; high CoE). S/V reduced NTproBNP (SMD = -0.34, 95% CI: -0.52 to -0.16; 3 RCTs; I2 = 62%) and hs-TNT (ratio of differences = 0.84, 95% CI: 0.79-0.88; 2 RCTs; I2 = 0%), and caused a decline in renal function by 33% (HR = 0.67, 95% CI: 0.39-1.14; 2 RCTs; I2 = 78%; high CoE). S/V in-creased hypotension (RR = 1.69, 95% CI: 1.33-2.15; 9 RCTs; I2 = 65%; high CoE). Hyperkalaemia and angioedema events were similar. Effects were in the same direction when stratified by type of control (ACEI vs. ARB).Conclusions: Sacubitril/valsartan had better clinical, intermediate, and renal outcomes in HF in comparison to ACEI or ARB. There was no difference in an-gioedema and hyperkalaemia events, but there were more hypotension events.