Sacubitril/Valsartan in the Treatment of Heart Failure With Reduced Ejection Fraction Focusing on the Impact on the Quality of Life: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

There exists a paucity of research data reported by analyses performed on randomized clinical trials (RCTs) that encompass quality of life (QOL) and the aftermath for patients suffering from heart failure with reduced ejection fraction (HFrEF). This systematic review and meta-analysis of randomized clinical trials (RCTs) have been done to evaluate the drug sacubitril/valsartan in the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) with a clear focus on the effect it bestows on measures of physical exercise tolerance and quality of life. A thorough systematic search was done in databases including Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Embase, and PubMed from 1 January 2010 to 1 January 2023. The search only included published RCTs on adult patients aged 18 and above, with heart failure with reduced ejection fraction (HFrEF). Data analysis was performed by using the software RevMan 5.4 (Cochrane Collaboration, London, United Kingdom). The included studies' bias risk was assessed using the Cochrane Collaboration's Risk of Bias tool. The quality of evidence for the primary outcome was done using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. This systematic review and meta-analysis of RCTs yielded 458 studies, of which eight randomized clinical trials were included and analyzed. The meta-analysis of the included trials shows that the I2 value is 61% (i.e., I2 > 50%), demonstrating a substantial heterogeneity within the studies. The left ventricular ejection fraction (LVEF) expressed in percentage was reported in the five studies, and thereby, a subgroup analysis that yielded a confidence interval (CI) of 95% had the standard mean difference of 0.02 (-0.02, 0.07). The trials had disparity between the reporting of effect on peak oxygen consumption (VO2 ), measured through cardiopulmonary exercise testing (CPET) methods, six-minute walking test (6MWT), overall physical activity, and exercise capacity. Sacubitril/valsartan did not exponentially improve peak VO2 or 6MWT in these trials; however, the patient-reported data suggested that the quality of life was modestly influenced by the drug. A subgroup analysis was performed using the pooled effect value by the random effects model. The findings showed that the sacubitril/valsartan group significantly was better than the control group in improving HFrEF-associated health-related quality of life (HRQoL). This study is a systematic review and meta-analysis of randomized clinical trials that evaluated the drug sacubitril/valsartan in treating heart failure with reduced ejection fraction (HFrEF) and focused on its tangible effect on the measures of physical exercise tolerance and quality of life. It depicts that the statistical scrutiny due to the lack of significant data and parity across studies did not impart significant improvement of either LVEF, peak VO2 , or 6MWT with the use of sacubitril/valsartan; however, the reported exercise tolerance, including daytime physical activity, had a modest impact with the said drug. The pooled values demonstrated that the sacubitril/valsartan group significantly outperformed the control group in improving HFrEF HRQoL.