Digoxin is associated with worse outcomes in patients with heart failure with reduced ejection fraction.

AIMS: The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline-recommended treatments in the real world in China. METHODS AND RESULTS: Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN-HF) were enrolled to assess the all-cause mortality, HF mortality, all-cause re-hospitalization, and HF re-hospitalization associated with digoxin use. Eight hundred eighty-two eligible HFrEF patients in the CN-HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow-up of 28.6 months. Kaplan-Meier survival analysis showed that the all-cause mortality (P < 0.001) and all-cause re-hospitalization (P = 0.020) were significantly higher in digoxin group than non-digoxin group, while HF mortality (P = 0.232) and HF re-hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional-hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all-cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27-2.44; P = 0.001] and all-cause re-hospitalization (HR 1.27; 95% CI 1.03-1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all-cause mortality irrespective of rhythm or in combination with other guideline-recommended therapies. CONCLUSIONS: Digoxin use is independently associated with increased risk of all-cause mortality and all-cause re-hospitalization in HFrEF patients.

Outcomes of patients with anemia and renal dysfunction in hospitalized heart failure with preserved ejection fraction (from the CN-HF registry).

BACKGROUND: Although a large number of studies on heart failure with reduced ejection fraction (HFrEF) have found that anemia and renal dysfunction (RD) independently predicted poor outcomes, there are still few reports on patients with heart failure with preserved ejection fraction (HFpEF). METHODS: Clinical data of HFpEF patients registered in the China National Heart Failure Registration Study (CN-HF) were evaluated and the clinical features of patients with or without anemia/RD were compared to explore the impact of anemia and RD on all-cause mortality and all-cause re-hospitalization. RESULTS: 1604 patients with HFpEF were enrolled, the prevalence of anemia was 51.0%. Although anemia was associated with increased risk of all-cause mortality and all-cause re-hospitalization in univariate COX regression (p < 0.05), multivariate COX model confirmed that anemia was not independently associated with all-cause mortality [hazard ratio (HR) 1.14, 95% confidence interval (CI) 0.85-1.52, p = 0.386] and all-cause re-hospitalization (HR 1.13, 95% CI 0.96-1.33, p = 0.152). Similarly, RD was not an independent predictor of all-cause mortality (HR 1.18, 95% CI 0.88-1.57, p = 0.269) and all-cause re-hospitalization (HR 0.94, 95% CI 0.79-1.12, p = 0.488) as assessed in the adjusted COX regression model. The interaction between RD and anemia on end-points events was also not statistically significant. However, anemia was associated with increased all-cause re-hospitalization in patients with New York Heart Association (NYHA) class III-IV. CONCLUSIONS: In patients with HFpEF from CN-HF registry, anemia was common, but was not an independent predictor of all-cause mortality and all-cause re-hospitalization, except for the all-cause re-hospitalization in patients with NYHA class III-IV.Clinical Trial Registration: http://www.clinicaltrials.gov/ct2/home; ID: NCT02079428.

Candesartan versus imidapril in hypertension: a randomised study to assess effects of anti-AT1 receptor autoantibodies.

BACKGROUND: Anti-angiotensin II receptor subtype 1 (AT1 receptor) autoantibodies have previously been shown in sera of hypertensive patients. This study assessed whether anti-AT1-receptor autoantibody in serum is correlated with the efficacy of an AT1-receptor blocker (ARB; candesartan)-based regimen in hypertensive patients after 8 weeks of treatment. DESIGN: The Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies is a multicentre, randomised, blinded endpoint, open-label, parallel-group comparison clinical trial conducted in five centres in Wuhan, China. Treatment is designed as stepwise added-on therapy to reduce blood pressure (BP) < 140/90 mm Hg. 512 patients with moderate to severe primary hypertension were randomly assigned to an 8-week treatment with either ARB (candesartan)-based regimen (n=257) or ACE inhibitor (imidapril)-based regimen (n=255). RESULTS: Systolic and diastolic BP was reduced significantly in both treatment groups. The candesartan-based regimen achieved a significantly greater systolic BP reduction than imdapril (30.8 ± 10.3 vs 28.8 ± 10.3 mm Hg, p = 0.023). In those anti-AT1 receptor autoantibody-positive hypertensive patients, the mean systolic BP at baseline was higher than in the anti-AT1 receptor autoantibody-negative group (160.5 ± 16.5 vs 156.2 ± 17.7 mm Hg; p = 0.006). The mean BP reduction was greater in the candesartan-based regimen than the imidapril-based regimen (-35.4 ± 9.8/16.9 ± 6.9 vs -29.4 ± 9.8/14.2 ± 6.9 mm Hg; p = 0.000 and 0.002, respectively), and more patients on imidapril required add-on medications to achieve BP control (94% vs 86%; p=0.03). No correlation was observed between the titre of anti-AT1 receptor autoantibody and the efficacy of candesartan-based therapy. In those anti-AT1 receptor autoantibody-negative patients similar BP lowering was reached in the candesartan and the imidapril-based regimens. CONCLUSIONS: An ARB-based regimen is more effective in BP lowering than an ACE inhibitor-based regimen in the presence of anti-AT1 receptor autoantibodies. Trial registration number This trial has been registered at http://www.register.clinicaltrials.gov/ (identifier: NCT00360763).