Gender differences in reverse cardiac remodeling following initiation of sacubitril/valsartan in heart failure with reduced ejection fraction: real world experience

Abstract

Abstract Background Gender related differences in physiology and pharamocokinetics have long been appreciated; however, the clinical relevance of these differences are unclear (1). Sacubitril/Valsartan has become established as a guideline directed therapy for the treatment of heart failure with reduced ejection therapy (HFref) and NYHA class II-IV symptoms. Interestingly; recent secondary analysis of key trials such as PARAGON-HF and PARADIGM, have highlighted possible differential gender specific benefits from Sacubitril/Valsartan therapy (2). We therefore sought to evaluate if there were gender specific effects of Sacubitril/Valsartan on both quantitative and qualitative measures of heart failure outcomes. Methods We performed a retrospective data interrogation of all patients commenced on Sacubitril/valsartan therapy in the SHSCT between 2016 and 2019. Data was extracted using electronic care records. Local ethical approval was granted. The primary endpoint were change in LVEF% on echocardiography and improvement in QOL (defined as NYHA score) at one year following initiation of Sacubitril/Valsartan. Differences in means between baseline and one year were assessed using a paired student's t-test. Interaction of gender on respective outcomes was assessed using a two way ANOVA. Significance defined as p<0.05. Data expressed as mean ± SD. Analysis performed using SPSS™. Results A total of 422 patients were included (mean age 69.1±12.1 years; 66% male). The predominant NYHA class' were II (n=298, 67.7%) and III (n=118, 26.8%). Aetiology and comorbidities were similar across male and females. In both groups, there was a statistically significant improvement in LVEF% at one year following initiation of Sacubitril/Valsartan (female; 27.1±8.6 to 34.6±9.5, n=40 p<0.01) (male; 27.4±7.5% to 32.6±9.3%, n=91, p<0.01). There was a statistically significant interaction between gender and degree of reverse cardiac remodeling defined as LVEF% on echocardiography following initiation of Sacubitril/Valsartan (F[2,52]=8.280, p=0.04, partial n2=0.27) (Figure 1). Similarly, there was a significant improvement in NYHA scores in both groups (male; 2.2±0.5 to 2.02±0.6, n=331, p<0.05) (female; 2.29±0.6 to 2.07±0.5, n=91, p<0.05) (Figure 2). However; there was no statistically significant interaction between gender and NYHA score following initiation of Sacubitril/Valsartan (F[2,52]=0.133, P=0.716, partial n2≤0.0). Conclusion Sacubitril/Valsartan produced significant improvement in reverse cardiac remodelling and QOL measures in both groups. Notably, had a stronger effect of reverse cardiac remodelling in women – suggesting possible gender specific differential benefits. Funding Acknowledgement Type of funding sources: None.