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Pharmacotherapy treatment patterns at hospital discharge and clinical outcomes among patients with heart failure with reduced ejection fraction.

ABSTRACT:

Background

This study aimed to assess the prescribing patterns of evidence-based pharmacotherapy and their association with clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in Thailand.

Methods

A retrospective cohort study of patients with HFrEF was conducted. Treatment with a β-blocker and renin-angiotensin system inhibitors (RASIs) with or without mineralocorticoid receptor antagonists (MRAs) at discharge was regarded as guideline-directed medical therapy (GDMT). All others were considered non-GDMT. The primary endpoint was the composite of all-cause mortality or heart failure (HF) rehospitalization. Inverse-probability-treatment-weighted adjusted Cox proportional hazard models were used to examine the treatment effects.

Results

In total, 653 patients with HFrEF (mean age 64.1 ± 14.3 years; 55.9% male) were included. GDMT with β-blockers and RASIs with or without MRAs was prescribed at a rate of 35.4%. During a median of 1-year follow-up, 167 patients (27.5%) had a composite event, 81 patients (13.3%) had all-cause mortality, and 109 patients (18.0%) had HF rehospitalization. Patients treated with GDMT at discharge showed significantly lower rates of the primary endpoint (adjusted hazard ratio [HR] 0.63; 95% CI 0.44-0.89; p = 0.009) compared with patients who did not receive GDMT. The use of GDMT was also associated with a significantly lower risk of all-cause mortality (adjusted HR 0.59; 95% CI 0.36-0.98; p = 0.045) and HF rehospitalization (adjusted HR 0.65; 95% CI 0.43-0.96; p = 0.031).

Conclusions

For HFrEF treatment, GDMT initiation at hospital discharge was associated with a significantly reduced risk of all-cause mortality and HF rehospitalization. Nevertheless, prescribing GDMT remains underused, and it could be encouraged to improve HF outcomes in real-world settings.

SUBMITTER: Wongsalap Y

PROVIDER: S-EPMC10249177 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Pharmacotherapy treatment patterns at hospital discharge and clinical outcomes among patients with heart failure with reduced ejection fraction.

Wongsalap Yuttana Y Poolpun Duangkamon D Keawhai Konrapee K Kitpluem Napusson N Pansiri Parichat P Malaimat Siriluck S Senthong Vichai V Kengkla Kirati K

Chronic diseases and translational medicine 20230208 2

<h4>Background</h4>This study aimed to assess the prescribing patterns of evidence-based pharmacotherapy and their association with clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in Thailand.<h4>Methods</h4>A retrospective cohort study of patients with HFrEF was conducted. Treatment with a β-blocker and renin-angiotensin system inhibitors (RASIs) with or without mineralocorticoid receptor antagonists (MRAs) at discharge was regarded as guideline-directed ...[more]

PMID: 37305111

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Project description:Heart failure is a common entity encountered in healthcare with a vast socioeconomic impact. Recent advances in pharmacotherapy have led to the development of novel therapies with mortality benefits, improvement in heart failure symptoms and hospitalizations. This article is intended to explore those newer pharmacotherapies and summarize the evidence behind guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF). It has been several years since any significant advances in pharmacotherapy of heart failure have resulted in survival benefit. Angiotensin-neprilysin inhibitors through the PARADIGM-HF and PIONEER-HF trials have shown mortality benefits and a reduction in heart failure hospitalizations and are considered landmark trials in heart failure. Vericiguat is an oral guanylate cyclase stimulator that through the recent VICTORIA trial showed a 10% relative difference in death from cardiovascular cause or hospitalization for heart failure. The sodium-glucose transport protein 2 (SGLT2) inhibitors are another class of medications that have shown promise in the treatment of patients with HFrEF and diabetes mellitus. The CANVAS and EMPA-REG OUTCOME trials showed the potential benefit of SGLT2 inhibitors on cardiovascular mortality, DECLARE-TIMI 58 trial showed that treatment with dapagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure to a greater extent in patients with reduced ejection fraction (EF). Although novel pharmacotherapy is the current focus of intense research, there have been numerous studies on potential benefit of iron supplementation in ferropenic patients with heart failure. Another rapidly expanding area of research in the realm of heart failure is precision medicine and its impact on the development, progression, and treatment of heart failure. The field of heart failure is dynamic and with the influx of data from recent and ongoing trials, newer therapies with morbidity and mortality benefits in HFrEF are now available, nonetheless, much work is still needed.

Project description:BackgroundGuideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials.ObjectivesWe investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF.Methods and resultsPatients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome.ConclusionsRASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.

Project description:Background Guidelines recommend using multiple drugs in patients with heart failure (HF) with reduced ejection fraction, but there is a paucity of real-world data on the simultaneous initiation of the 4 pharmacological pillars at discharge after a decompensation event. Methods and Results A retrospective data mart, including patients diagnosed with HF, was implemented. Consecutively admitted patients with HF with reduced ejection fraction were selected through an automated approach and categorized according to the number/type of treatments prescribed at discharge. The prevalence of contraindications and cautions for HF with reduced ejection fraction treatments was systematically assessed. Logistic regression models were fitted to assess predictors of the number of treatments (≥2 versus <2 drugs) prescribed and the risk of rehospitalization. A population of 305 patients with a first episode of HF hospitalization and a diagnosis of HF with reduced ejection fraction (ejection fraction, <40%) was selected. At discharge, 49.2% received 2 current recommended drugs, β-blockers were prescribed in 93.4%, while a renin-angiotensin system inhibitor or an angiotensin receptor-neprilysin inhibitor was prescribed in 68.2%. A mineralocorticoid receptor antagonist was prescribed in 32.5%, although none of the patients showed contraindications to mineralocorticoid receptor antagonist prescription. A sodium-glucose cotransporter 2 inhibitor could be prescribed in 71.1% of patients. On the basis of current recommendations, 46.2% could receive the 4 foundational drugs at discharge. Renal dysfunction was associated with <2 foundational drugs prescribed. After adjusting for age and renal function, use of ≥2 drugs was associated with lower risk of rehospitalization during the 30 days after discharge. Conclusions A quadruple therapy could be directly implementable at discharge, potentially providing prognostic advantages. Renal dysfunction was the main prevalent condition limiting this approach.

Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.

Project description:BackgroundThe deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented.ObjectivesThe authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists.MethodsOf the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled.ResultsFour-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778).ConclusionsAmong hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes.

Project description:AimsHeart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Methods and resultsPatients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P < 0.001).ConclusionsAmongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.

Dataset Information

Pharmacotherapy treatment patterns at hospital discharge and clinical outcomes among patients with heart failure with reduced ejection fraction.

Background

Methods

Results

Conclusions

Publications

Pharmacotherapy treatment patterns at hospital discharge and clinical outcomes among patients with heart failure with reduced ejection fraction.

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