Dataset Information

Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry.

ABSTRACT:

Background

Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection.

Objective

In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)].

Methods

Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF ≤ 57% (i.e. median). We defined reduced EF/PARADIGM-HF as EF < 40%, mildly reduced EF/PARAGON-HF ≤ median as EF 40-49%, and normal EF/PARAGON-HF > median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario).

Results

Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes.

Conclusion

In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered.

SUBMITTER: Savarese G

PROVIDER: S-EPMC7984286 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsIn 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 resultsEligibility 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.ConclusionsIn 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.

Project description:BackgroundGuidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data.ObjectivesThis study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan.MethodsUsing 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects.ResultsAverage age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex.ConclusionsBaseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Project description:Background Dyslipidemia is common in heart failure with preserved ejection fraction. Sacubitril/valsartan improves glycemic control and augments natriuretic peptide signaling, providing mechanisms by which sacubitril/valsartan may affect serum lipids. However, empiric data on these effects are lacking. Methods and Results We analyzed 4774 participants from PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) with available screening lipids. During follow-up visits, we analyzed the treatment effect on lipid levels and assessed for interaction by baseline lipid levels. At the 16-week visit, we adjusted these treatment effects for the change in several biomarkers (including hemoglobin A1c and urinary cyclic guanosine monophosphate/creatinine [a biomarker of natriuretic peptide activation]). The average age was 73±8 years, 52% were women, 43% had diabetes mellitus, and 64% were on statin therapy. Compared with valsartan, sacubitril/valsartan reduced triglycerides -5.0% (95% CI, -6.6% to -3.5%), increased high-density lipoprotein cholesterol +2.6% (95% CI, +1.7% to +3.4%), and increased low-density lipoprotein cholesterol +1.7% (95% CI, +0.4% to +3.0%). Sacubitril/valsartan reduced triglycerides most among those with elevated baseline levels (triglycerides≥200 mg/dL) (P-interaction<0.001), and at 16 weeks by -13.0% (95% CI, -18.1% to -7.6%), or -29.9 (95% CI, -44.3 to -15.5) mg/dL, in this group. Adjusting for the change in urinary cyclic guanosine monophosphate/creatinine significantly attenuated treatment effects on triglycerides and high-density lipoprotein cholesterol, but not low-density lipoprotein cholesterol, while adjusting for other biomarkers did not significantly alter the treatment effects. Conclusions Sacubitril/valsartan significantly reduces triglycerides compared with valsartan, an effect that was nearly threefold stronger in those with elevated baseline triglycerides. Modest increases in high-density lipoprotein cholesterol and low-density lipoprotein cholesterol cholesterol were also observed with therapy. The underlying mechanism(s) of changes in high-density lipoprotein cholesterol and triglycerides are related to sacubitril/valsartan's effects on natriuretic peptide activity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.