Patients Not Meeting PARADIGM-HF Enrollment Criteria Are Eligible for Sacubitril/Valsartan on the Basis of FDA Approval

Pérez, Antonio L.; Kittipibul, Veraprapas; Tang, W.H. Wilson; Starling, Randall C.

doi:10.1016/j.jchf.2017.03.007

Cited by 12 publications

(15 citation statements)

References 3 publications

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“…However, for LCZ696, NP levels were used in the trial, in guidelines and by some countries and payers, so they are still relevant for stakeholders trying to interpret real‐world implementation. Furthermore, and considering the big difference that we showed in outcome rates among patients fulfilling the NP vs. all other exclusion criteria, it is conceivable that the risk/benefit ratio is different in patients not having sufficiently high NP criteria, and even probable that cost‐effectiveness is quantitatively different . NPs do not appear to be routinely measured in real‐world HFrEF outpatients once the diagnosis has been established, as demonstrated by the high number of missing entries in the present study and other registries .…”

Section: Discussionmentioning

confidence: 66%

“…When the ACEi/ARB dose criterion (20 mg daily), which was most rare to be met, was set to half dose, the proportion of patients eligible significantly increased to 28% with either the PARADIGM‐HF or the ESC guideline criteria. Low rates of eligibility have been previously reported in smaller studies with fewer and less generalizable centres: the proportion of patients considered suitable for LCZ696 according to the FDA drug label ranged between 50% and 71% of patients, whereas the respective proportion when the PARADIGM‐HF criteria (20 mg daily ACEi/ARB dose) were applied decreased to 21–39% . However, if the 10 mg ACEi/ARB dose criterion was alternatively used, rates of eligibility again significantly rose .…”

Section: Discussionmentioning

confidence: 85%

“…Low rates of eligibility have been previously reported in smaller studies with fewer and less generalizable centres: the proportion of patients considered suitable for LCZ696 according to the FDA drug label ranged between 50% and 71% of patients, whereas the respective proportion when the PARADIGM‐HF criteria (20 mg daily ACEi/ARB dose) were applied decreased to 21–39% . However, if the 10 mg ACEi/ARB dose criterion was alternatively used, rates of eligibility again significantly rose . The only exception seems to come from the Swedish Heart Failure Registry; symptomatic (NYHA class II–IV) HFrEF patients were prescribed enalapril ≥ 10 mg or equivalent in 74.4% and enalapril ≥ 20 mg or equivalent in 50.0% of cases.…”

Section: Discussionmentioning

confidence: 92%

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Sacubitril/valsartan eligibility and outcomes in the ESC‐EORP‐HFA Heart Failure Long‐Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM‐HF trial, ESC guidelines, and real world

Lainščak

Savarese

Laroche

et al. 2019

European J of Heart Fail

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Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM‐HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC‐EORP‐HFA Long‐Term Heart Failure (HF‐LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM‐HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM‐HF and guideline criteria, respectively. Absent PARADIGM‐HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub‐optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub‐optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM‐HF and guidelines. One‐year heart failure hospitalization was higher (12% and 17% vs. 12%) and all‐cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM‐HF. Conclusions Among outpatients with HFrEF in the ESC‐EORP‐HFA HF‐LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM‐HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM‐HF enalapril group.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 92%

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Sacubitril/valsartan eligibility and outcomes in the ESC‐EORP‐HFA Heart Failure Long‐Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM‐HF trial, ESC guidelines, and real world

Lainščak

Savarese

Laroche

et al. 2019

European J of Heart Fail

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“…A prior study applied the eligibility criteria of the PARADIGM‐HF trial to 210 patients hospitalized with acute or chronic HFrEF at the Cleveland Clinic with available follow‐up data within 30 days of discharge 3. Of these 210 patients, 71% were eligible for sacubitril/valsartan at the follow‐up appointment on the basis of Food and Drug Administration labeling criteria, yet only 26% were eligible for enrollment in the PARADIGM‐HF trial on the basis of the trial eligibility criteria.…”

Section: Discussionmentioning

confidence: 99%

“…The specific inclusion and exclusion criteria of the PARADIGM‐HF trial (eg, patients with history of symptomatic hypotension or systolic blood pressure [SBP] <95 mm Hg at randomization were excluded) and the sequential active run‐in period have led to concerns that PARADIGM‐HF trial participants were a highly select population of patients with chronic HFrEF 3. To understand how patients randomized in the PARADIGM‐HF trial may or may not be reflective of those routinely encountered in current clinical practice, we compared the baseline characteristics of patients in the PARADIGM‐HF trial with those in the CHAMP‐HF (Change the Management of Patients With Heart Failure) study a large US outpatient registry of patients with HFrEF with limited inclusion and exclusion criteria.…”

Section: Introductionmentioning

confidence: 99%

Characteristics and Treatments of Patients Enrolled in the CHAMP‐HF Registry Compared With Patients Enrolled in the PARADIGM‐HF Trial

DeVore

Thomas

et al. 2018

JAHA

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BackgroundThe US Food and Drug Administration approved sacubitril/valsartan for patients with chronic heart failure (HF) with reduced ejection fraction in 2015 on the basis of the results of the PARADIGM‐HF (Prospective Comparison of ARNI [Angiotensin Receptor Neprilysin Inhibitor] With ACEI [Angiotensin‐Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. There are limited data assessing the generalizability of PARADIGM‐HF trial participants to a broader population of patients with HF with reduced ejection fraction routinely encountered in outpatient clinical practice.Methods and ResultsWe compared the baseline characteristics of patients in the PARADIGM‐HF trial with those in the CHAMP‐HF (Change the Management of Patients With Heart Failure) study a large US outpatient registry of patients with HF with reduced ejection fraction. Patients in the PARADIGM‐HF trial (n=8442) were similar to those in the CHAMP‐HF registry (n=3497) in terms of age (mean, 64 versus 66 years), sex (22% versus 29% women), New York Heart Association class III to IV (25% versus 32%), systolic blood pressure (mean, 121 versus 121 mm Hg), left ventricular ejection fraction (mean, 29% versus 29%), and other key baseline characteristics. The median (25th–75th percentile) Meta‐Analysis Global Group in Chronic Heart Failure risk scores were similar for the 2 studies (20 [16–24] versus 22 [8–27]). Despite this, only 13% of patients in the CHAMP‐HF registry were prescribed sacubitril/valsartan at baseline.ConclusionsThese data suggest participants randomized in the PARADIGM‐HF trial have similar baseline characteristics to those encountered in routine outpatient clinical practice, but there is a substantial lag in the adoption of sacubitril/valsartan for patients with chronic HF with reduced ejection fraction.

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Applicability of US Food and Drug Administration Labeling for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in US Clinical Practice

et al. 2021

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2020, dapagliflozin was approved by the US Food and Drug Administration (FDA) as the first sodium-glucose cotransporter 2 inhibitor for heart failure with reduced ejection fraction (HFrEF), based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. Limited data are available characterizing the generalizability of dapagliflozin to US clinical practice. OBJECTIVE To evaluate candidacy for initiation of dapagliflozin based on the FDA label among contemporary patients with HFrEF in the US.DESIGN, SETTING, AND PARTICIPANTS This cohort study included 154 714 patients with HFrEF (left ventricular ejection fraction Յ40%) hospitalized at 406 sites in the Get With the Guidelines-Heart Failure (GWTG-HF) registry admitted between January 1, 2014, and September 30, 2019. Patients who left against medical advice, transferred to an acute care facility or to hospice, or had missing data were excluded. The FDA label (which excluded patients with an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m 2 , those undergoing dialysis, and those with type 1 diabetes) was applied to the GWTG-HF registry sample. Data analyses were conducted from April 1 to June 30, 2020. MAIN OUTCOMES AND MEASURESThe proportion of patients hospitalized with HFrEF who would be candidates for dapagliflozin under the FDA label. RESULTS Among 154 714 patients hospitalized with HFrEF, 125 497 (81.1%; 83 481 men [66.5%]; mean [SD] age, 68 [15] years) would be candidates for dapagliflozin according to the FDA label. Across 355 sites with patients with 10 or more hospitalizations, the median proportion of candidates for dapagliflozin according to the FDA label was 81.1% (interquartile range, 77.8%-84.6%) at each site. This proportion was similar across all study years (interquartile range, 80.4%-81.7%) and was higher among those without type 2 diabetes than with type 2 diabetes (85.5% vs 75.6%). Among GWTG-HF participants, the most frequent reason for not meeting the FDA label criteria was eGFR less than 30 mL/min/1.73 m 2 at discharge (18.5%). Among 75 654 patients with available paired admission and discharge data, 14.2% had an eGFR less than 30 mL/min/1.73 m 2 at both time points, while 3.8% developed an eGFR less than 30 mL/min/1.73 m 2 by discharge. Although there were more older adults, women, and Black patients in the GWTG-HF registry than in the DAPA-HF trial, most clinical characteristics were qualitatively similar between the 2 groups. Compared with the DAPA-HF trial cohort, there was lower use of evidence-based HF therapies among patients in GWTG-HF.CONCLUSIONS AND RELEVANCE These data from a large, contemporary US registry of patients hospitalized with heart failure suggest that 4 of 5 patients with HFrEF (with or without type 2 diabetes) would be candidates for initiation of dapagliflozin, supporting its broad generalizability to US clinical practice.

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Patients Not Meeting PARADIGM-HF Enrollment Criteria Are Eligible for Sacubitril/Valsartan on the Basis of FDA Approval

Cited by 12 publications

References 3 publications

Sacubitril/valsartan eligibility and outcomes in the ESC‐EORP‐HFA Heart Failure Long‐Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM‐HF trial, ESC guidelines, and real world

Sacubitril/valsartan eligibility and outcomes in the ESC‐EORP‐HFA Heart Failure Long‐Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM‐HF trial, ESC guidelines, and real world

Characteristics and Treatments of Patients Enrolled in the CHAMP‐HF Registry Compared With Patients Enrolled in the PARADIGM‐HF Trial

Applicability of US Food and Drug Administration Labeling for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in US Clinical Practice

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