RESUMEN
BACKGROUND: Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding the frequency, timing or predictors of early treatment discontinuation in clinical practice. METHODS: Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with > 5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation. RESULTS: Over median follow-up of 18 months, frequency of drug discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.7% (444 of 3509 users), 10.4% (140 of 1352 users), and 20.4% (435 of 2129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEis/ARBs, and 447 (12.7%) of ACEi/ARB users were switched to ARNIs during follow-up. Across sites, the median proportion of discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.5% (25th-75th percentiles 6.9%-18.9%), 18.8% (25th-75th percentiles 12.5%-28.6%), and 19.6% (25th-75th percentiles 10.7%-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P < 0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEis/ARBs and ARNIs (both P < 0.001) but not of MRAs. Investigator clinical experience was predictive of lower risks of discontinuation of ACEis/ARBs and MRAs (P < 0.02) but not of ARNIs. All other independent predictors of discontinuation were unique to individual therapeutic classes. CONCLUSIONS: One in 10 patients discontinue ACEis/ARBs or ARNIs, and 1 in 5 discontinue MRAs in routine clinical practice of heart failure with reduced ejection fraction. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.
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Antagonistas de Receptores de Angiotensina , Insuficiencia Cardíaca , Aldosterona/farmacología , Aldosterona/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Angiotensinas/farmacología , Angiotensinas/uso terapéutico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Humanos , Renina/farmacología , Renina/uso terapéutico , Sistema Renina-Angiotensina , Volumen SistólicoRESUMEN
Importance: It is unclear how New York Heart Association (NYHA) functional class compares with patient-reported outcomes among patients with heart failure (HF) in contemporary US clinical practice. Objective: To characterize longitudinal changes and concordance between NYHA class and the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS), and their associations with clinical outcomes. Design, Setting, and Participants: This cohort study included 2872 US outpatients with chronic HF with reduced ejection fraction across 145 practices enrolled in the CHAMP-HF registry between December 2015 and October 2017. All patients had complete NYHA class and KCCQ-OS data at baseline and 12 months. Longitudinal changes and correlations between the 2 measure were examined. Multivariable models landmarked at 12 months evaluated associations between improvement in NYHA and KCCQ-OS from baseline to 12 months with clinical outcomes occurring from months 12 through 24. Statistical analyses were performed from March to August 2020. Exposure: Change in health status, as defined by 12-month change in NYHA class or KCCQ-OS. Main Outcomes and Measures: All-cause mortality, HF hospitalization, and mortality or HF hospitalization. Results: In total, 2872 patients were included in this analysis (median [interquartile range] age, 68 [59-75] years; 872 [30.4%] were women; and 2156 [75.1%] were of White race). At baseline, 312 patients (10.9%) were NYHA class I, 1710 patients (59.5%) were class II, 804 patients (28.0%) were class III, and 46 patients (1.6%) were class IV. For KCCQ-OS, 1131 patients (39.4%) scored 75 to 100 (best health status), 967 patients (33.7%) scored 50 to 74, 612 patients (21.3%) scored 25 to 49, and 162 patients (5.6%) scored 0 to 24 (worst health status). At 12 months, 1002 patients (34.9%) had a change in NYHA class (599 [20.9%] with improvement; 403 [14.0%] with worsening) and 2158 patients (75.1%) had a change of 5 or more points in KCCQ-OS (1388 [48.3%] with improvement; 770 [26.8%] with worsening). The most common trajectory for NYHA class was no change (1870 [65.1%]), and the most common trajectory for KCCQ-OS was an improvement of at least 10 points (1047 [36.5%]). After adjustment, improvement in NYHA class was not associated with subsequent clinical outcomes, whereas an improvement of 5 or more points in KCCQ-OS was independently associated with decreased mortality (hazard ratio, 0.59; 95% CI, 0.44-0.80; P < .001) and mortality or HF hospitalization (hazard ratio, 0.73; 95% CI, 0.59-0.89; P = .002). Conclusions and Relevance: Findings of this cohort study suggest that, in contemporary US clinical practice, compared with NYHA class, KCCQ-OS is more sensitive to clinically meaningful changes in health status over time. Changes in KCCQ-OS may have more prognostic value than changes in NYHA class.
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Insuficiencia Cardíaca/fisiopatología , Hospitalización/estadística & datos numéricos , Mortalidad , Volumen Sistólico/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Anciano , Causas de Muerte , Femenino , Insuficiencia Cardíaca/clasificación , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/clasificación , Disfunción Ventricular Izquierda/terapiaRESUMEN
BACKGROUND: In patients stabilized during hospitalization for acute decompensated heart failure (HF), initiation of sacubitril/valsartan compared with enalapril decreased the risk of cardiovascular death or rehospitalization for HF without increasing the risk of adverse events. It is unknown whether potentially high-risk subpopulations have a similar risk-benefit profile. METHODS: PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP [N-terminal pro-B type natriuretic peptide] in Patients Stabilized From an Acute HF Episode) was a multicenter, randomized, double-blind trial of in-hospital initiation of sacubitril/valsartan (n=440) versus enalapril (n=441) in patients stabilized during hospitalization for acute decompensated HF. The composite of cardiovascular death or rehospitalization for HF was adjudicated. Safety outcomes included worsening renal function, symptomatic hypotension, and hyperkalemia. We evaluated heterogeneity in the effect of sacubitril/valsartan on these efficacy and safety outcomes in selected subgroups of clinical concern: patients with baseline systolic blood pressure ≤118 mm Hg (median; n=448), baseline NT-proBNP >2701 pg/mL (median; n=395), estimated glomerular filtration rate <60 mL/minute per 1.73 m2 (n=455), ≥1 additional hospitalization for HF within the prior year (n=343), admission to the ICU during the index hospitalization (n=96), inotrope use during the index hospitalization (n=68), and severe congestion (n=219). RESULTS: The relative risk reduction in cardiovascular death or rehospitalization for HF with sacubitril/valsartan versus enalapril was consistent across all high-risk subgroups (P interaction=non-significant [NS] for each). The risks of worsening renal function, symptomatic hypotension, and hyperkalemia with sacubitril/valsartan versus enalapril were also consistent in each high- versus low-risk subgroup (P interaction=NS for each). CONCLUSIONS: In high-risk subpopulations admitted for acute decompensated HF, treatment with sacubitril/valsartan after initial stabilization conferred a consistent reduction in cardiovascular death or rehospitalization for HF and was well tolerated.
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Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Valsartán/uso terapéutico , Enfermedad Aguda , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Cardiotónicos/uso terapéutico , Enfermedad Crónica , Combinación de Medicamentos , Enalapril/uso terapéutico , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Humanos , Hiperpotasemia/inducido químicamente , Hipotensión/inducido químicamente , Hipotensión/fisiopatología , Unidades de Cuidados Intensivos , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Insuficiencia Renal/sangre , Insuficiencia Renal/complicaciones , RiesgoRESUMEN
OBJECTIVES: The authors sought to evaluate the association of heart failure hospitalization (HFH) with guideline-directed medical therapy (GDMT) prescribing patterns among patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: HFH represents an important opportunity to titrate GDMT among patients with HFrEF. METHODS: The CHAMP-HF (Change the Management of Patients With Heart Failure) registry is a prospective registry of adults with HFrEF (ejection fraction ≤40%). Using data from the CHAMP-HF registry (N = 4,365), adjusted time-to-event models were created to study the association of HFH with GDMT prescribing patterns. RESULTS: HFH (compared with no HFH) was positively associated with initiation of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor, beta-blocker, and mineralocorticoid receptor antagonist (MRA). HFH positively associated with dose escalation of ACE inhibitor/ARB (probability ratio: 1.71, 95% confidence interval [CI]: 1.36 to 2.16) and MRA (probability ratio: 8.71, 95% CI: 4.19 to 18.10). In those on prior therapy, HFH was associated with discontinuation and de-escalation of all classes of GDMT. ACE inhibitor/ARB, angiotensin receptor-neprilysin inhibitor, beta-blocker, and MRA de-escalation/discontinuation after HFH was associated with increased risk of all-cause mortality with hazard ratios of 3.82 (95% CI: 2.42 to 6.03), 4.76 (95% CI: 2.06 to 11.03), 2.94 (95% CI: 2.04 to 4.25), and 4.81 (95% CI: 2.61 to 8.87), respectively. CONCLUSIONS: HFH positively associated with changes in GDMT, including initiation, dose escalation, discontinuation, and dose de-escalation. De-escalation/discontinuation of GDMT after HFH associated with increased risk of all-cause mortality. Educational endeavors are needed to ensure GDMT is not inappropriately held in the setting of HFH. For those in whom GDMT must be held/decreased, improvement tools at discharge and post-discharge titration clinics may help ensure lifesaving GDMT regimens remain optimized.
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Insuficiencia Cardíaca , Adulto , Cuidados Posteriores , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización , Humanos , Alta del Paciente , Volumen SistólicoRESUMEN
AIMS: The aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We leveraged data from CHAMP-HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 Overall Summary Scale (range from 0 to 100; ≥20-point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient-level characteristics as well as baseline KCCQ-12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ-12 score of 0-60 points had an OR = 0.86/5-point higher score (CI 0.79, 0.93)], and those with a KCCQ-12 score of 60-80 points had an OR = 0.61/5-point higher score (0.45-0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05). CONCLUSIONS: We found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy-particularly in those with worse symptoms, function, and quality of life-and assessing treatment response are likely to be the best prospective strategy.
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Insuficiencia Cardíaca , Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Estado de Salud , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Estudios Prospectivos , Calidad de Vida , Sistema de Registros , Volumen Sistólico , ValsartánRESUMEN
BACKGROUND: In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) versus enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice. METHODS: PROVIDE-HF was a prospective study within a national research network (Patient-Centered Outcomes Research Network) of HFrEF outpatients recently initiated on sacubitril/valsartan versus controls with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change. The primary end point was mean Kansas City Cardiomyopathy Questionnaire (KCCQ) change through 12â¯weeks. Other end points included responder analyses: ≥5-point and ≥20-point KCCQ increase. Adjusted QOL change was estimated after propensity score weighting. RESULTS: Overall, 270 patients had both baseline and 12-week KCCQ data (151 sacubitril/valsartan; 119 control). The groups had similar demographics and HF details: median EF 28% and N-terminal pro-brain natriuretic peptide 1083â¯pg/mL. Sacubitril/valsartan patients had larger improvements in KCCQ (mean difference +4.76; Pâ¯=â¯.027) and were more likely to have aâ¯≥5-point andâ¯≥20-point response (all Pâ¯<â¯.05). Adjusted comparisons demonstrated similar numerical improvements in the change in KCCQ (+4.55; 95% CI -0.89 to 9.99; Pâ¯=â¯.101) and likelihood of ≥5-point increase (odds ratio 1.55; 95% CI: 0.84-2.86; Pâ¯=â¯.16); ≥20-point increase remained statistically significant (odds ratio 3.79; 95% CI 1.47-9.73; Pâ¯=â¯.006). CONCLUSIONS: In this prospective HFrEF study of sacubitril/valsartan initiation compared with recent angiotensin-converting enzyme inhibitor/angiotensin receptor blocker initiation/dose change, the between-group difference in the primary end point, mean KCCQ change at 12â¯weeks was not statistically significant following adjustment, but sacubitril/valsartan initiation was associated with early improvements in QOL and a higher likelihood of ≥20-point improvement in KCCQ at 12â¯weeks. These data add additional real-world evidence related to patient-reported outcomes following the initiation of sacubitril/valsartan in routine clinical practice.
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Aminobutiratos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Datos Preliminares , Calidad de Vida , Tetrazoles/uso terapéutico , Anciano , Aminobutiratos/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Compuestos de Bifenilo , Estudios de Casos y Controles , Combinación de Medicamentos , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Puntaje de Propensión , Estudios Prospectivos , Tetrazoles/administración & dosificación , ValsartánRESUMEN
OBJECTIVES: This study compared the efficacy and safety of sacubitril/valsartan to enalapril in Black and non-Black Americans with acute decompensated heart failure (ADHF). BACKGROUND: Black patients have a different response to treatment with angiotensin-converting enzyme inhibitors compared with other racial and ethnic groups. How Black patients with ADHF respond to sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is unclear. PIONEER-HF was a double-blind randomized clinical trial of sacubitril/valsartan versus enalapril in hospitalized patients with ADHF following hemodynamic stabilization. METHODS: In a pre-specified subgroup analysis, we examined changes in N-terminal pro-B-type natriuretic peptide, clinical outcomes, and safety according to race. RESULTS: The study population, all enrolled in the United States, included 316 (36%) Black participants, 515 (58%) White participants, and 50 (5.7%) participants of other racial groups. The reduction in N-terminal pro-B-type natriuretic peptide concentration at weeks 4 and 8 was significantly greater with sacubitril/valsartan than enalapril in both Black (ratio of change with sacubitril/valsartan vs. enalapril: 0.71; 95% confidence interval [CI]: 0.58 to 0.88) and non-Black patients (ratio of change: 0.71; 95% CI: 0.61 to 0.83; interaction p = 1.00). Compared with enalapril, sacubitril/valsartan also reduced the pre-specified exploratory composite of cardiovascular death or HF rehospitalization in both Black (hazard ratio: 0.47; 95% CI: 0.24 to 0.93) and non-Black patients (hazard ratio: 0.65; 95% CI: 0.40 to 1.06; interaction p = 0.44). CONCLUSIONS: Among Black patients admitted with ADHF in the United States, the in-hospital initiation of sacubitril/valsartan was more effective than enalapril in reducing natriuretic peptide levels and the composite of cardiovascular death or HF rehospitalization. The effect of sacubitril/valsartan did not differ by race. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Enalapril , Insuficiencia Cardíaca , Neprilisina , Valsartán , Negro o Afroamericano , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Angiotensinas , Compuestos de Bifenilo/uso terapéutico , Combinación de Medicamentos , Enalapril/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etnología , Humanos , Valsartán/uso terapéuticoRESUMEN
BACKGROUND: The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction. OBJECTIVES: The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results. METHODS: The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission. RESULTS: At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro-B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups. CONCLUSIONS: Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
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Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Neprilisina/antagonistas & inhibidores , Sistema Renina-Angiotensina/efectos de los fármacos , Anciano , Aminobutiratos/administración & dosificación , Compuestos de Bifenilo , Muerte , Método Doble Ciego , Combinación de Medicamentos , Enalapril/administración & dosificación , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Neprilisina/fisiología , Estudios Prospectivos , Receptores de Angiotensina/fisiología , Sistema Renina-Angiotensina/fisiología , Tetrazoles/administración & dosificación , ValsartánRESUMEN
OBJECTIVES: This study sought to evaluate the efficacy and safety of sacubitril/valsartan according to dose level achieved in the PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode) trial. BACKGROUND: In patients hospitalized for acute decompensated heart failure (ADHF), in-hospital initiation and continuation of sacubitril/valsartan as compared with enalapril is well tolerated, achieves a greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP), and reduces the risk of cardiovascular death or rehospitalization for HF through 8 weeks. However, not all patients achieve the target dose of sacubitril/valsartan, and its efficacy and safety in such patients are of interest. METHODS: PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan versus enalapril in 881 patients stabilized during hospitalization for ADHF. Blinded study medication was administered for 8 weeks, with initial dosing selected based on the systolic blood pressure at randomization and titrated toward a target of sacubitril/valsartan 97/103 mg twice daily, or enalapril 10 mg twice daily, with an algorithm based on systolic blood pressure and the investigator's assessment of tolerability. RESULTS: At 4 weeks, 199 (55%) patients allocated to sacubitril/valsartan and 211 (60%) patients allocated to enalapril were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. There was no heterogeneity across dose levels in the effect of sacubitril/valsartan on the reduction in NT-proBNP (pinteraction = 0.69), the reduction in cardiovascular death or rehospitalization for heart failure (pinteraction = 0.42), or the pre-specified adverse events of special interest through 8 weeks. CONCLUSIONS: In hemodynamically stabilized patients with ADHF, the efficacy and safety of sacubitril/valsartan are generally consistent across dose levels. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Insuficiencia Cardíaca , Valsartán , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina , Compuestos de Bifenilo/uso terapéutico , Combinación de Medicamentos , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Volumen Sistólico , Valsartán/uso terapéutico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Among patients with heart failure (HF) with reduced ejection fraction (EF), improvements in left ventricular EF (LVEF) are associated with better outcomes and remain an important treatment goal. Patient factors associated with LVEF improvement in routine clinical practice have not been clearly defined. METHODS: CHAMP-HF (Change the Management of Patients with Heart Failure) is a prospective registry of outpatients with HF with reduced EF. Assessments of LVEF are recorded when performed for routine care. We analyzed patients with both baseline and ≥1 follow-up LVEF assessments to describe factors associated with LVEF improvement. RESULTS: In CHAMP-HF, 2623 patients had a baseline and follow-up LVEF assessment. The median age was 67 (interquartile range, 58-75) years, 40% had an ischemic cardiomyopathy, and median HF duration was 2.8 years (0.7-6.8). Median LVEF was 30% (23-35), and median change on follow-up was 4% (-2 to -13); 19% of patients had a decrease in LVEF, 31% had no change, 49% had a ≥5% increase, and 34% had a ≥10% increase. In a multivariable model, the following factors were associated with ≥5% LVEF increase: shorter HF duration (odds ratio [OR], 1.21 [95% CI, 1.17-1.25]), no implantable cardioverter defibrillator (OR, 1.46 [95% CI, 1.34-1.55]), lower LVEF (OR, 1.15 [95% CI, 1.10-1.19]), nonischemic cardiomyopathy (OR, 1.24 [95% CI, 1.09-1.36]), and no coronary disease (OR, 1.20 [95% CI, 1.03-1.35]). CONCLUSIONS: In a large cohort of outpatients with chronic HF with reduced EF, improvements in LVEF were common. Common baseline cardiac characteristics identified a population that was more likely to respond over time. These data may inform clinical decision making and should be the basis for future research on myocardial recovery.
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Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico , Anciano , Atención Ambulatoria , Enfermedad Crónica , Estudios de Cohortes , Progresión de la Enfermedad , Ecocardiografía , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Sistema de Registros , Volumen Sistólico/fisiología , Resultado del TratamientoRESUMEN
OBJECTIVES: The purpose of this study was to characterize the clinical profile, treatment patterns, and clinical outcomes of patients with comorbid diabetes mellitus (DM) and heart failure with reduced ejection fraction (HFrEF) in a contemporary, real-world U.S. outpatient registry in the context of evolving treatment strategies. BACKGROUND: Specific antihyperglycemic classes have differential risks and benefits with respect to HF. Limited data are available evaluating contemporary treatment patterns and outcomes of patients with comorbid DM and HFrEF. METHODS: Among 4,970 patients with chronic HFrEF (≤40%) across 152 U.S. sites in the CHAMP-HF prospective, observational registry (2015 to 2017), we examined therapies and clinical outcomes by DM status. RESULTS: Median age was 68 (58 to 75) years of age; 29% were women; 73.5% were white; and 64% had coronary artery disease. Overall, 42% (n = 2,085) had comorbid DM with a median hemoglobin A1c (HbA1c) level of 7.2% (interquartile range [IQR]: 6.4% to 8.3%). One-fourth of DM patients (24%) were not treated with an antihyperglycemic therapy. Most patients with DM were taking 1 (46%) or 2 (23%) antihyperglycemic therapies: metformin (40%); insulin (33%); sulfonylureas (24%); dipeptidyl peptidase-4 inhibitors (10%); glucagon-like peptide (GLP)-1 receptor agonists (4%); sodium-glucose cotransporter (SGLT)-2 inhibitors (2%); and thiazolidinediones (2%). Among patients with DM, 62%, 16%, 80%, and 33.5% were receiving any angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), ß-blockers, or mineralocorticoid receptor antagonists (MRAs) at baseline, respectively. Among patients without DM, corresponding baseline rates were 65%, 15%, 80%, and 37%, respectively. Patients with or without DM were infrequently treated with guideline-directed HFrEF therapies at target doses (≤27% across classes). During median 15-month follow-up, patients with DM experienced higher rates of all-cause mortality or HF hospitalization (30% vs. 23%, respectively), independent of 11 pre-specified covariates (adjusted hazard ratio: 1.35 (95% confidence interval: 1.21 to 1.52); p < 0.001). CONCLUSIONS: Despite higher risk-adjusted clinical event rates in patients with comorbid HFrEF and DM, guideline-directed medical therapies for both disease states are incomplete and represent an important target for quality improvement through multidisciplinary care pathways.
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Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus/epidemiología , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Volumen Sistólico/fisiología , Anciano , Comorbilidad , Femenino , Estudios de Seguimiento , Adhesión a Directriz , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios/estadística & datos numéricos , Estudios Prospectivos , Sistema de Registros , Factores de Tiempo , Resultado del TratamientoRESUMEN
Importance: In PIONEER-HF, among stabilized patients with acute decompensated heart failure (ADHF), the in-hospital initiation of sacubitril/valsartan was well tolerated and led to improved outcomes compared with enalapril. However, there are limited data comparing the strategies of in-hospital vs postdischarge initiation of sacubitril/valsartan. Objective: To describe changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients recently hospitalized for ADHF and switching from taking enalapril to taking sacubitril/valsartan after discharge and compare clinical outcomes for patients randomized to receive in-hospital initiation of sacubitril/valsartan vs in-hospital initiation of enalapril who later switched to taking sacubitril/valsartan during an open-label extension phase. Interventions: Sacubitril/valsartan titrated to 97/103 mg twice daily. Design, Setting, and Participants: The PIONEER-HF trial was a multicenter, randomized, double-blind, active-controlled trial conducted at 129 US sites between May 2016 and May 2018 that compared the in-hospital initiation of sacubitril/valsartan vs enalapril (titrated to target dose, 10 mg twice daily) for 8 weeks among patients admitted for ADHF with reduced ejection fraction and hemodynamic stability. All patients were to continue in a 4-week, open-label study of sacubitril/valsartan; of 881 patients enrolled in PIONEER-HF, 832 (94%) continued in the open-label study. Main Outcomes and Measures: Changes in NT-proBNP levels from week 8 to 12 as well as the exploratory composite of heart failure rehospitalization or cardiovascular death from randomization through week 12. Results: Of 881 participants, 226 (27.7%) were women, 487 (58.5%) were white, 297 (35.7%) were black, 15 (1.8%) were Asian, and 73 (8.8%) were of Hispanic ethnicity; the mean (SD) age was 61 (14) years. For patients who continued to take sacubitril/valsartan, NT-proBNP levels declined -17.2% (95% CI, -3.2 to -29.1) from week 8 to 12. The NT-proBNP levels declined to a greater extent for those switching from taking enalapril to sacubitril/valsartan after the week 8 visit (-37.4%; 95% CI, -28.1 to -45.6; P < .001; comparing changes in 2 groups). Over the entire 12 weeks of follow-up, patients that began taking sacubitril/valsartan in the hospital had a lower hazard for the composite outcome compared with patients that initiated enalapril in the hospital and then had a delayed initiation of sacubitril/valsartan 8 weeks later (hazard ratio, 0.69; 95% CI 0.49-0.97). Conclusions and Relevance: Switching patients' treatment from enalapril to sacubitril/valsartan at 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with heart failure with reduced ejection fraction and a recent hospitalization for ADHF. Trial Registration: ClinicalTrials.gov identifier: NCT02554890.
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Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/análisis , Neprilisina/antagonistas & inhibidores , Fragmentos de Péptidos/análisis , Tetrazoles/uso terapéutico , Enfermedad Aguda , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Compuestos de Bifenilo , Combinación de Medicamentos , Enalapril/uso terapéutico , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente , ValsartánRESUMEN
Underuse of hydralazine/nitrate (HYD/NIT) in black patients with heart failure and reduced ejection fraction (HFrEF) has been previously described, but whether this important treatment gap persists in contemporary practice is unknown. Sacubitril/valsartan has become a part of guideline-directed medical therapy for HFrEF but data on utilization of this therapy in black patients is lacking. This study addressed these issues by assessing the frequency of HYD/NIT and sacubitril/valsartan use in black patients with HFrEF in the Change the Management of Patients with Heart Failure Registry, a multicenter cohort study. The association of race with utilization rates of these agents was also evaluated. Clinical and medication data at baseline and during 12 months of follow-up from black and nonblack registry patients without documented contraindications or intolerance to the medications of interest were analyzed. Data were available from December 2015 to October 2017, in 4,848 HFrEF patients, of whom 853 were black (18%) and 3995 were nonblack. Black patients were younger, more likely to be female, and had lower ejection fractions compared with nonblacks. Only 11% of black patients were receiving HYD/NIT therapy at baseline and 13% at 1 year. The percentage of black patients treated at baseline with sacubitril/valsartan was also low at 18% and remained unchanged at 1 year. After adjustment for covariates, race was independently associated with HYD/NIT use (odds ratio 8.32; 95% confidence interval 6.12 to 11.3; p < 0.0001), but not for sacubitril/valsartan. In conclusion, study findings demonstrate a marked persistent treatment gap for HYD/NIT and similar poor utilization of sacubitril/valsartan in black patients with HFrEF despite current guideline recommendations.
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Negro o Afroamericano/estadística & datos numéricos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etnología , Hidralazina/uso terapéutico , Neprilisina/uso terapéutico , Sistema de Registros , Anciano , Aminobutiratos/administración & dosificación , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo , Estudios de Cohortes , Combinación de Medicamentos , Utilización de Medicamentos , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Volumen Sistólico/efectos de los fármacos , Tasa de Supervivencia , Tetrazoles/administración & dosificación , Resultado del Tratamiento , ValsartánRESUMEN
OBJECTIVES: This study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF). BACKGROUND: Although therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients' symptoms, functions, and quality of life is unknown. METHODS: Health status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status. RESULTS: Multivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p < 0.001) over a median (interquartile range [IQR]) of 57 (32 to 104) days. The proportions of ARNI versus no-ARNI groups with ≥10-point (large) and ≥20-point (very large) improvements in KCCQ-OS were 32.7% versus 26.9%, respectively, and 20.5% versus 12.1%, respectively, consistent with numbers needed to treat of 18 and 12, respectively. CONCLUSIONS: In routine clinical care, ARNI therapy was associated with early improvements in health status, with 20% experiencing a very large health status benefit compared with 12% who were not started on ARNI therapy. These findings support the use of ARNI to improve patients' symptoms, functions, and quality of life.
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Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Neprilisina/antagonistas & inhibidores , Volumen Sistólico , Tetrazoles/uso terapéutico , Anciano , Compuestos de Bifenilo , Estudios de Cohortes , Combinación de Medicamentos , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , ValsartánRESUMEN
OBJECTIVES: The aim of this study was to use a multicenter, observational outpatient registry of patients with heart failure with reduced ejection fraction (HFrEF) to describe the association between changes in patients' medications with changes in health status. BACKGROUND: Alleviating symptoms and improving function and quality of life for patients with HFrEF are primary treatment goals and potential indicators of quality. Whether titrating medications in routine clinical care improves patients' health status is unknown. METHODS: The association of any change in HFrEF medications with 3-month change in health status, as measured using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Scale, was determined in unadjusted and multivariate-adjusted (25 clinical characteristics, baseline health status) models using hierarchical linear regression. RESULTS: Among 3,313 outpatients with HFrEF from 140 centers, 21.9% had medication changes. Three months later, 23.7% and 46.4% had clinically meaningfully worse (≥5-point decrease) and improved (≥5-point increase) Kansas City Cardiomyopathy Questionnaire Overall Summary Scale scores. The 3-month median change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scale score for patients whose HFrEF medications were changed was significantly larger (7.3 points; interquartile range: -3.1 to 20.8 points) than in patients whose medications were not changed (3.1 points; interquartile range: -4.7 to 12.5 points) (adjusted difference 3.0 points; 95% confidence interval: 1.4 to 4.6 points; p < 0.001). Among patients whose medications were adjusted, 26% had very large clinical improvement (≥20 points) compared with 14% whose regimens were not changed. CONCLUSIONS: In routine care of patients with HFrEF, changes in HFrEF medications were associated with significant improvements in patients' health status, suggesting that health status-based performance measures can quantify the benefits of titrating medicines in patients with HFrEF.
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Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Calidad de Vida , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diuréticos/uso terapéutico , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Neprilisina/antagonistas & inhibidores , Sistema de RegistrosRESUMEN
AIMS: Circulating high-sensitivity cardiac troponin (hsTn) and soluble ST2 (sST2) reflect myocardial stress in patients with heart failure (HF). Production of cyclic guanosine 3'5' monophosphate (cGMP) in response to activation of natriuretic peptide receptors reduces cardiac afterload and preload. We assessed the effects of sacubitril/valsartan on these biomarkers in patients with reduced ejection fraction and acute decompensated HF (ADHF). METHODS AND RESULTS: PIONEER-HF was a randomized, double-blind trial of sacubitril/valsartan vs. enalapril in hospitalized patients with ADHF following haemodynamic stabilization. We measured circulating hsTnT, sST2, and urinary cGMP at baseline, 1, 2 (sST2, cGMP), 4, and 8 weeks (n = 694 with all baseline biomarkers). Ratios of geometric means (timepoint/baseline) were determined and compared as a ratio for sacubitril/valsartan vs. enalapril. Compared with enalapril, sacubitril/valsartan led to a significantly greater decline in hsTnT and sST2. This effect emerged as early as 1 week for sST2 and was significant for both at 4 weeks with a 16% greater reduction in hsTnT (P < 0.001) and 9% greater reduction in sST2 (P = 0.0033). Serial urinary cGMP increased with sacubitril/valsartan compared with enalapril (P < 0.001, 1 week). The significant differences between treatment groups for each biomarker were sustained at 8 weeks. In an exploratory multivariable-adjusted analysis of cardiovascular death or HF-rehospitalization, the concentrations of hsTnT, sST2 at week 1 were significantly associated with subsequent outcome. CONCLUSION: Biomarkers of myocardial stress are elevated in patients with ADHF and associated with outcome. Compared with enalapril, sacubitril/valsartan reduces myocardial injury and haemodynamic stress as reflected by biomarkers, with an onset that is apparent within 1-4 weeks. CLINICAL TRIALS REGISTRATION: NCT02554890 clinical.trials.gov.
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Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Enalapril/uso terapéutico , Insuficiencia Cardíaca , Tetrazoles/uso terapéutico , Anciano , Biomarcadores/sangre , Compuestos de Bifenilo , GMP Cíclico/orina , Combinación de Medicamentos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Hemodinámica , Humanos , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Troponina/sangre , ValsartánAsunto(s)
Aminobutiratos/uso terapéutico , Enalapril/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico , Compuestos de Bifenilo , Método Doble Ciego , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/metabolismo , Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown. OBJECTIVES: This study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes. METHODS: Among 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up. RESULTS: At baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months, <1% of patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA. In multivariate analysis, across the classes of medications, multiple patient characteristics were associated with a higher likelihood of initiation or dose increase (e.g., previous HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation or dose decrease (e.g., previous HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common reasons for discontinuations and dose decreases of each therapy, but the relative contributions from patient preference, health team, and systems-based reasons varied by medication. CONCLUSIONS: In this contemporary U.S. registry, most eligible HFrEF patients did not receive target doses of medical therapy at any point during follow-up, and few patients had doses increased over time. Although most patients had no alterations in medical therapy, multiple clinical factors were independently associated with medication changes. Further quality improvement efforts are urgently needed to improve guideline-directed medication titration for HFrEF.
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Insuficiencia Cardíaca/tratamiento farmacológico , Disfunción Ventricular Izquierda/tratamiento farmacológico , Anciano , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Volumen SistólicoRESUMEN
OBJECTIVES: This study sought to determine the rate of use of target doses of foundational guideline-directed medical therapy (GDMT) in a contemporary cohort of patients with heart failure with reduced ejection fraction (HFrEF) across systolic blood pressure (SBP) categories. BACKGROUND: Patients with HFrEF are infrequently titrated to recommended doses of GDMT. The relationship between SBP and achieving GDMT target doses is not well studied. METHODS: Patients enrolled in the CHAMP-HF (Change the Management of Patients With Heart Failure) registry without documented intolerance to angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta blockers (BBs) were assessed at enrollment. We estimated the proportion receiving target doses (% of target dose [95% confidence interval (CI)]) based on the most recent American College of Cardiology/American Heart Association/Heart Failure Society of America heart failure guidelines at baseline in all patients, and by SBP category (≥110 vs. <110 mm Hg). RESULTS: Of the 3,095 patients eligible for analysis, 2,421 (78.2%) had SBP ≥110 mm Hg. The proportion of patients receiving target doses were 18.7% (95% CI: 17.3% to 20.0%; BB), 10.8% (95% CI: 9.7% to 11.9%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.5%; ARNI). Among those with SBP <110 mm Hg (n = 674), 17.5% (95% CI: 14.6% to 20.4%; BB), 6.2% (95% CI: 4.4% to 8.1%; ACEI/ARB), and 1.8% (95% CI: 0.8% to 2.8%; ARNI) were receiving target doses. Among those with SBP ≥110 mm Hg (n = 2,421), 19.0% (95% CI: 17.4% to 20.6%; BB), 12.1% (95% CI: 10.8% to 13.4%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.6%; ARNI) were receiving target doses. CONCLUSIONS: In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BBs and ACEI/ARB/ARNI, <20% of patients were receiving target doses, even among those with SBP ≥110 mm Hg.