Kosztin, Annamária

Abstract Aims To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial. Methods and results A total of 4796 participants ≥50 years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) ≥45% were divided into three age groups: <65 years (n = 825), 65–74 years (n = 1772), and ≥75 years (n = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory. The primary composite outcome was total HF hospitalizations and cardiovascular (CV) death. Older patients were more likely to experience primary composite outcomes (compared to patients <65 years, adjusted rate ratio [aRR] for ≥75 years: 1.39, 95% confidence interval [CI] 1.21–1.61), total HF hospitalization (aRR 1.27, 95% CI 1.09–1.49), and CV death (adjusted hazard ratio [aHR] 2.04, 95% CI 1.44–2.87). Age did not modify the effect of sacubitril/valsartan compared to valsartan on primary composite endpoint (pinteraction = 0.79) in the overall population or in those with LVEF ≤57%. Older adults randomized to sacubitril/valsartan were more likely to develop hypotension compared to those receiving valsartan (pinteraction = 0.026). Older patients had smaller left ventricular chamber sizes, higher LVEF, and were more likely to have abnormal measures of diastolic function. Conclusion Older patients with HF with preserved ejection fraction had higher event rates than younger patients, more adverse events overall, and more hypotension when treated with sacubitril/valsartan; however, the treatment benefits of sacubitril/valsartan were retained in older patients.

Introduction: Heart failure with preserved ejection fraction (HFpEF) may have different characteristics by age groups. Aim Compare clinical and echocardiographic characteristics in patients with HFpEF enrolled in the PARAGON-HF echocardiography substudy by age groups. Methods: Echocardiography was performed in 1097 patients in PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction), where patients with left ventricular ejection fraction (LVEF) >=45% were enrolled. Clinical and echocardiographic characteristics were compared in patients who were <65, 65-74, and >75 years of age. Results: Younger patients were more likely to be male, obese, have prior myocardial infarction (MI) and diabetes, but less likely to have atrial fibrillation (AF, Table 1). Older patients had smaller left ventricular (LV) dimension indices, more likely to have concentric hypertrophy or remodeling, higher LVEF and better global longitudinal strain, and more likely to have left atrial enlargement and echocardiographic evidence of higher LV filling pressure (Table 1). Echocardiographic measures of pulmonary pressure and right ventricular function were similar across age groups. After adjusting for sex, race, region, history of MI, diabetes, AF, and body mass index, every 10 years of increase in age was associated with 5.1 mL/m 2 decrease in LV end-diastolic volume index (95% confidence interval [CI] 3.9 - 6.5, p < 0.001), 0.4% increase in absolute global longitudinal strain (95% CI 0.1% - 0.7%, p = 0.017), and 1.07 increase in E/e’ septal ratio (95% CI 0.42 - 1.73, p = 0.001). Conclusions: Compared with younger patients, older patients with HFpEF were more likely to be female with AF, have better systolic function and higher LV filling pressure. These findings demonstrated the heterogeneity in cardiac structure and function in HFpEF by age and may have implications for treatment and future clinical trial recruitment.

Background: Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men. Methods: In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Results: Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro–B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59–0.90) in women and 1.03 (95% CI, 0.84–1.25) in men ( P interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men. Conclusions: As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. Clinical Trial Registration: https://www.clinicaltrials.gov . Unique identifier: NCT01920711.