Meta-Analysis: The Effectiveness of Sacubitril/Valsartan Versus Ace Inhibitors in Heart Failure with Reduced Ejection Fraction (Hfref)

Despite significant advancements in medical therapy and evolution of guideline directed management, heart failure with reduced ejection fraction (HFrEF) still remains a significant clinical and economic burden on a global scale. Based on new data obtained from randomized controlled trials and real-world, sacubitril/valsartan (S/V), a novel angiotensin receptor–neprilysin inhibitor (ARNI), has been suggested as a better substitute for conventional renin-angiotensin-aldosterone system inhibitors, especially angiotensin-converting enzyme inhibitors (ACEIs). The purpose of this meta-analysis is to assess and contrast the efficacy and clinical outcome of S/V and ACEIs in patients with HFrEF. In this meta-analysis, total of 19 studies, comprising both randomized controlled trials and observational cohorts were evaluated to generate results. These studies covered population from various ethnicities and age groups, having different co-morbidities. Mortality, heart failure-related hospitalizations, functional class improvement (NYHA), echocardiographic parameters, renal outcomes and tolerability were among the primary outcomes evaluated. The pooled risk ratio (RR) for S/V versus ACEIs which was determined by using a fixed- effects model, was 0.70 (95% CI: 0.53–0.93), suggesting a statistically and clinically significant superiority of sacubitril/valsartan therapy on ACEIs. S/V proved better in lowering mortality, limiting rehospitalization, maintaining renal function, and improving patients' satisfaction than ACEIs, and this effect was consistently seen across different subgroups. These results not only support the findings of pivotal trials like PARADIGM- HF, but also show its clinical relevance when it comes to under-represented populations in traditional trials, such as patients with advanced chronic kidney disease, veterans, and Middle Eastern cohorts. Most importantly, even in high-risk subgroups like the elderly, children and people with renal dysfunction, S/V proved to be safer and more tolerable. Although S/V patients experienced hypotension more frequently, the advantages in terms of survival and functional outcomes outweighed the risk. Aligned with important international guidelines, the current meta-analysis supports sacubitril/valsartan as a first-line treatment for HFrEF symptoms. Improvements in outcomes like mortality and hospitalization rates endorse the idea of its wider implementation in both clinical trials and real world practice settings.