Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON‐HF trial. (22nd November 2021)

• Record Type: Journal Article
• Authors: Lund, Lars H.; Savarese, Gianluigi; Venkateshvaran, Ashwin; Benson, Lina; Lundberg, Anna; Donal, Erwan; Daubert, Jean‐Claude; Oger, Emmanuel; Linde, Cecilia; Hage, Camilla
• Is Part Of: ESC heart failure. Volume 9:Number 1(2022)
• Page Start: 164
• Page End: 177
• Publication Date: 2021-11-22
• Subjects: Heart failure with preserved ejection fraction -- Heart failure with mid‐range ejection fraction -- Heart failure with mildly reduced ejection fraction -- Heart failure with borderline ejection fraction -- PARAGON‐HF -- Sacubitril/valsartan -- Eligibility -- Echocardiography -- Structural heart disease -- Trial design; Heart failure -- Periodicals; 616.129005
• DOI: 10.1002/ehf2.13705
• Languages: English
• ISSNs: 2055-5822

Abstract

Abstract: Aims: In the heart failure (HF) with preserved ejection fraction (HFpEF) PARAGON‐HF trial, sacubitril/valsartan vs. valsartan improved mortality/morbidity in patients with left ventricular ejection fraction (LVEF) below median (57%). We assessed eligibility for sacubitril/valsartan based on four scenarios. Methods and results: Eligibility was assessed in the Karolinska‐Rennes study (acute HFpEF, LVEF ≥ 45%, and N‐terminal pro‐B‐type natriuretic peptide ≥300 pg/mL subsequently assessed as outpatients including echocardiography) in (i) a trial scenario (all trial criteria); (ii) a pragmatic scenario (selected trial criteria); (iii) LVEF below lower limit of normal range (<54% in women and <52% in men); and (iv) LVEF below mean of normal range (<64% in women and <62% in men). Among 425 patients [age 78 (72–83) years, 57% women, 28% LVEF ≤ 57% (median in PARAGON‐HF), the trial scenario, identified 34% as eligible. Left atrial enlargement and/or left ventricular hypertrophy were present in 99%. Inclusion criteria not met were diuretic treatment and New York Heart Association class. Important exclusion criteria were estimated glomerular filtration rate <30 mL/min/1.73 m 2, haemoglobin <10 g/day, and cancer. In the pragmatic scenario, 63% were eligible. In LVEF below lower limit of normal range, 5.4% were eligible, and in LVEF below mean of normal range, 41% were eligible. In patients with LVEF ≤ 57%, eligibility was 42%, 69%, 21%, and 91% according to the trial scenario, pragmatic scenario, LVEF below lower limit of normal range, and LVEF below mean of normal range, respectively. Conclusions: In real‐world HFpEF (LVEF ≥ 45%) with N‐terminal pro‐B‐type natriuretic peptide and cardiac structure/function assessed, eligibility for sacubitril/valsartan was according to PARAGON‐HF complete criteria 34%, pragmatic criteria 63%, LVEF below lower limit of normal range 5.4%, and LVEF below mean of normal range 41%. Cardiac structural impairment was almost ubiquitous. Ineligibility was more due to exclusion criteria than failing to meet inclusion criteria.