scholarly journals Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction After a Recent Worsening Heart Failure Event

Author(s):  
Anthony P. Carnicelli ◽  
Robert Clare ◽  
Paul Hofmann ◽  
Karen Chiswell ◽  
Adam D. DeVore ◽  
...  

Background Contemporary trials of patients with heart failure with reduced ejection fraction (HFrEF) required a recent worsening heart failure (WHF) event for inclusion. We aimed to describe characteristics and outcomes of patients with HFrEF and a recent WHF event at a large tertiary referral center. Methods and Results We identified adult patients with chronic symptomatic HFrEF (ejection fraction ≤35%) treated at Duke University between January 1, 2009, and December 31, 2018, and applied a set of exclusion criteria to generate a cohort similar to those enrolled in contemporary heart failure trials. Patients were stratified by presence or absence of a recent WHF event, defined as an emergency department visit for heart failure or hospitalization for heart failure in the prior 12 months. Characteristics and outcomes including death and hospitalization were assessed. Of 3867 patients with HFrEF meeting study criteria, 2823 (73.0%) had a WHF event in the prior 12 months. Compared with patients without a WHF event, those with a WHF event were more likely to be under‐represented racial and ethnic groups and had lower ejection fraction, a greater burden of comorbidities, and more echocardiographic evidence of cardiac dysfunction. Despite higher use of guideline‐directed therapies, patients with a WHF event had higher rates of death (hazard ratio, 2.30; 95% CI, 2.01–2.63), all‐cause hospitalization (hazard ratio, 1.56; 95% CI, 1.42–1.71), and heart failure hospitalization (hazard ratio, 1.59; 95% CI, 1.44–1.75) through 5 years compared with those without a recent WHF event. Conclusions WHF events are common in patients with HFrEF and are associated with more advanced disease. Patients with recent WHF have high rates of death and hospitalization, underscoring the need for novel therapies in this large subgroup of patients with HFrEF.

Author(s):  
Milton Packer ◽  
Stefan D. Anker ◽  
Javed Butler ◽  
Gerasimos S. Filippatos ◽  
João Pedro Ferreira ◽  
...  

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure. Methods: We randomly assigned 3730 patients with class II-IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite endpoints. Results: Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 vs 519 patients; empagliflozin vs placebo, respectively; hazard ratio 0.76, 95% CI: 0.67-0.87), P <0.0001. This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio 0.67, 95% CI 0.50-0.90, P=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (hazard ratio 0.64, 95% CI: 0.47-0.87, P=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 vs 414), hazard ratio 0.67, 95% CI: 0.56-0.78, P<0.0001. Additionally, patients assigned to empagliflozin were 20-40% more likely to experience an improvement in NYHA functional class and were 20-40% less likely to experience worsening of NYHA functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (hazard ratio 0.70, 95% CI: 0.63-0.78), P<0.0001. Conclusions: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03057977


Circulation ◽  
2020 ◽  
Vol 142 (11) ◽  
pp. 1040-1054 ◽  
Author(s):  
Alice M. Jackson ◽  
Pooja Dewan ◽  
Inder S. Anand ◽  
Jan Bělohlávek ◽  
Olof Bengtsson ◽  
...  

Background: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. Methods: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. Results: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36–0.92), 0.83 (95% CI, 0.63–1.10), 0.77 (95% CI, 0.60–0.99), and 0.78 (95% CI, 0.63–0.97), respectively ( P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68–0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. Conclusions: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anthony P CARNICELLI ◽  
Robert M Clare ◽  
Paul Hofmann ◽  
Karen Chiswell ◽  
Adam D Devore ◽  
...  

Background: Several recent heart failure trials enrolled patients with heart failure with reduced ejection fraction (HFrEF) who had a worsening heart failure (WHF) event. Aim: To describe the characteristics and outcomes of patients with HFrEF and a WHF event at a large tertiary medical center. Methods: We identified patients 18-85 years of age with chronic symptomatic HFrEF (EF ≤35% and ≥2 HF encounters in the prior 18 months) treated at Duke University between Jan 2009-Dec 2018 through the Duke Echo Lab Database. A WHF event was defined as either a hospitalization or ED visit for HF in the prior 12 mos. A set of exclusion criteria [e.g., renal dysfunction, left ventricular assist device (LVAD), heart transplant] were applied to patients with a WHF event to generate a patient cohort similar to those enrolled in contemporary HF trials. We did not restrict the cohort based on BP or BNP levels since these vary over time. Baseline characteristics and outcomes including death and hospitalization were assessed. Results: Of 4846 unique patients with HFrEF, 3668 (76%) had a WHF event in the year prior to index echo. Sequentially, patients with GFR <20 mL/min/1.73 m 2 (n=458), LVAD (n=291), or heart transplant (n=95) were excluded; 2824/4846 (58%) remained in the WHF study population. HFrEF patients with WHF were typically men (68%) with median age of 65 years (IQR 54, 73) and low EF (EF <25% in 57%). Coronary disease (71%), diabetes (44%), and elevated NT-proBNP (median 2405 pg/mL [698, 6841]) were common. Beta-blocker, ACEi/ARB, and MRA use were 88%, 79% and 44%, respectively. HFrEF patients with WHF had a high 30-day, 1-year, and 5-year cumulative incidence of all-cause mortality and HF hospitalization after index echo (FIGURE). Conclusions: In patients with chronic HFrEF at Duke University, 76% had a WHF event in the past year and 58% met several of the key eligibility criteria of contemporary HF trials. Patients with recent WHF had a high burden of comorbidities and very high event rates.


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