ABSTRACT
BACKGROUND: In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF). MATERIALS AND METHODS: Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo. RESULTS: Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7±96.3m (Commencement), 317.0±126.1m (Week 12), 307.0±84.4m (Week 24); p=0.86), but almost reached statistical significance in the placebo group from 328.8±79.6m, to 361.6±98.2m and 384.0±74.9m (Week 24); p=0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3±16.7mmHg [Commencement], 45.3±13.9mmHg [Week 12], to 44.6±14.5mmHg [Week 24]; p=0.014) as did right atrial pressure (13.1±5.3 [Commencement], 10.0±3.8 [Week 12], to 9.4±3.2 [Week 24]; p=0.046). CONCLUSION: Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.
Subject(s)
Endothelin Receptor Antagonists/administration & dosage , Heart Failure, Diastolic/drug therapy , Hypertension, Pulmonary/drug therapy , Sulfonamides/administration & dosage , Aged , Bosentan , Endothelin Receptor Antagonists/adverse effects , Heart Failure, Diastolic/complications , Heart Failure, Diastolic/physiopathology , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Pilot Projects , Sulfonamides/adverse effectsABSTRACT
AIMS: Guidelines have been published for improving management of chronic heart failure (CHF). We examined the association between improved guideline adherence and risk for all-cause death in patients with stable systolic HF. METHODS: Data on ambulatory patients (2006-2010) with CHF and reduced ejection fraction (HF-REF) from the Austrian Heart Failure Registry (HIR Austria) were analysed. One-year clinical data and long-term follow-up data until all-cause death or data censoring were available for 1014 patients (age 65 [55-73], male 75%, NYHA class I 14%, NYHA II 56%, NYHA III/IV 30%). A guideline adherence indicator (GAI [0-100%]) was calculated for each patient at baseline and after 12 ± 3 months that considered indications and contraindications for ACE-I/ARB, beta blockers, and MRA. Patients were considered ΔGAI-positive if GAI improved to or remained at high levels (≥ 80%). ΔGAI50+ positivity was ascribed to patients achieving a dose of ≥ 50% of suggested target dose. RESULTS: Improvements in GAI and GAI50+ were associated with significant improvements in NYHA class and NT-proBNP (1728 [740-3636] to 970 [405-2348]) (p<0.001). Improvements in GAI50+, but not GAI, were independently predictive of lower mortality risk (HR 0.55 [95% CI 0.34-0.87; p=0.01]) after adjustment for a large variety of baseline parameters and hospitalisation for heart failure during follow-up. CONCLUSIONS: Improvement in guideline adherence with particular emphasis on dose escalation is associated with a decrease in long-term mortality in ambulatory HF-REF subjects surviving one year after registration.
