PARAGON-HF Clinical Trial Eligibility in a Population of Patients Hospitalized With Heart Failure

Sayeed, Sabina; Fudim, Marat; DeVore, Adam D.; Xu, Haolin; Matsouaka, Roland; Heidenreich, Paul A.; Yancy, Clyde W.; Fonarow, Gregg C.; Hernandez, Adrian F.

doi:10.1016/j.cardfail.2019.10.003

Cited by 5 publications

(9 citation statements)

References 6 publications

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“…In KaRen, the median age of eligible patients according to the trial scenario was 79 years. This is similar to the Swedish Heart Failure Registry (SwedeHF) 13 and the American Get With the Guidelines-Heart Failure registry (GWTG-HF) 19 where mean age was 77 and 79 years, respectively, whereas mean age in PARAGON-HF was 74 years. 20 In an analysis of the SwedeHF including 16 306 patients with LVEF ≥ 40%, 22% were eligible according to a PARAGON-HF trial scenario and 52% in a pragmatic scenario.…”

Section: Eligibilitysupporting

confidence: 75%

“…In an analysis of the SwedeHF including 16 306 patients with LVEF ≥ 40%, 22% were eligible according to a PARAGON‐HF trial scenario and 52% in a pragmatic scenario 13 . In a similar analysis in 106 440 patients in the GWTG‐HF registry, only 10% met all trial inclusion/exclusion criteria while 71% met a broader set of criteria 19 . However, in these registries, echocardiographic variables (except for LVEF) were not available and subsequently not considered among the inclusion criteria.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with HFpEF are at high risk for CV and HF events, especially the weeks after hospitalization 27 . When assessing eligibility based on trial inclusion/exclusion criteria for sacubitril/valsartan in HF populations after a hospitalization with acute decompensated HF, the eligibility has been low at 2–12% 19,28–30 . The limitation in eligibility may be due to the high proportion of coexisting co‐morbidities such as renal dysfunction and hyperkalaemia or a minimum daily dose of angiotensin‐converting enzyme inhibitor/ARB, or excluding patients with ongoing HF hospitalizations as in PARADIGM‐HF.…”

Section: Discussionmentioning

confidence: 99%

“… 13 In a similar analysis in 106 440 patients in the GWTG‐HF registry, only 10% met all trial inclusion/exclusion criteria while 71% met a broader set of criteria. 19 However, in these registries, echocardiographic variables (except for LVEF) were not available and subsequently not considered among the inclusion criteria. The KaRen study has the advantage of enrolling ‘real‐world’ patients but also collecting detailed echocardiographic and clinical characteristics, whereas registries might enrol larger and more unselected populations but lack this granularity.…”

Section: Discussionmentioning

confidence: 99%

“… 27 When assessing eligibility based on trial inclusion/exclusion criteria for sacubitril/valsartan in HF populations after a hospitalization with acute decompensated HF, the eligibility has been low at 2–12%. 19 , 28 , 29 , 30 The limitation in eligibility may be due to the high proportion of coexisting co‐morbidities such as renal dysfunction and hyperkalaemia or a minimum daily dose of angiotensin‐converting enzyme inhibitor/ARB, or excluding patients with ongoing HF hospitalizations as in PARADIGM‐HF. The angiotensin‐converting enzyme inhibitor/ARB criterion is strictly limited to HFrEF patients and is likely not applied in practice in HFmrEF and HFpEF, but the others are of interest also in these patient groups.…”

Section: Discussionmentioning

confidence: 99%

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Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON‐HF trial

et al. 2021

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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 m2, 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.

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Section: Eligibilitysupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON‐HF trial

et al. 2021

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Potential Implications of Expanded US Food and Drug Administration Labeling for Sacubitril/Valsartan in the US

et al. 2021

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and Drug Administration (FDA) expanded labeling for sacubitril/valsartan for use in individuals with chronic heart failure (HF) with left ventricular ejection fraction (LVEF) lower than normal. The population-level implications of implementation of sacubitril/valsartan at higher LVEF ranges is unknown. While the Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF) trial did not meet its primary end point, the trial may provide useful information in projecting expected clinical events among treated individuals.OBJECTIVE To quantify newly eligible treatment candidates for sacubitril/valsartan under the expanded FDA labeling and to apply treatment effects and the number needed to treat (NNT) to prevent 1 worsening HF event derived from subgroups of the PARAGON-HF trial who fall under the revised FDA label.DESIGN, SETTING, AND PARTICIPANTS Newly eligible treatment candidates were estimated by mapping the LVEF distribution from 559 520 adult patients hospitalized between 2014 and 2019 in the Get With The Guidelines-Heart Failure registry to adults self-identifying with HF in the National Health and Nutrition Examination Survey (2015 to 2018). The NNT with 3 years of treatment for 3 end points of interest (total HF hospitalizations, total HF hospitalizations and cardiovascular death, and total HF hospitalizations and urgent HF visits and cardiovascular death) were estimated from the PARAGON-HF trial. Data were analyzed from February to June 2021. MAIN OUTCOMES AND MEASURESNumber of worsening HF events prevented or postponed if eligible patients were treated with sacubitril/valsartan for 3 years. RESULTSOf an estimated 4 682 098 adults, the mean (SE) age was 66.3 (0.8) years, 1 995 037 (42.6%) were women, and 748 045 (16.0%) were Black. The potential number of adults projected to be newly eligible varied by the definition of FDA labeling of lower than normal LVEF from 643 161 (95% CI, 534 433-751 888; LVEF of 41% to 50%) to 1 838 756 (95% CI, 1 527 911-2 149 601; LVEF of 41% to 60%). In the PARAGON-HF trial, the NNT to prevent a worsening HF event (range, 7 to 12 patients) was consistent irrespective of specific LVEF range selected. Comprehensive implementation of sacubitril/valsartan among newly eligible patients was empirically estimated to prevent up to 69 268 (95% CI, 57 558-80 978) worsening HF events (LVEF of 41% to 50%) to 182 592 (95% CI, 151 725-213 460) worsening HF events (LVEF of 41% to 60%). CONCLUSIONS AND RELEVANCEThe expanded FDA labeling is positioned to substantially increase the potential HF population eligible for sacubitril/valsartan by up to 1.8 million individuals and has the potential to prevent or postpone as many as 180 000 worsening HF events, depending on the definition of normal LVEF.

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PARAGON-HF - considerations for potential use of sacubitril-valsartan in real-world heart failure with mildly reduced ejection fraction

Lund

Savarese

2019

Journal of Cardiac Failure

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PARAGON-HF Clinical Trial Eligibility in a Population of Patients Hospitalized With Heart Failure

Cited by 5 publications

References 6 publications

Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON‐HF trial

Eligibility of patients with heart failure with preserved ejection fraction for sacubitril/valsartan according to the PARAGON‐HF trial

Potential Implications of Expanded US Food and Drug Administration Labeling for Sacubitril/Valsartan in the US

PARAGON-HF - considerations for potential use of sacubitril-valsartan in real-world heart failure with mildly reduced ejection fraction

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