Ify R Mordi1, Wouter Ouwerkerk2,3, Stefan D Anker4, John G Cleland5, Kenneth Dickstein6,7, Marco Metra8, Leong L Ng9, Nilesh J Samani9, Dirk J van Veldhuisen10, Faiez Zannad11, Adriaan A Voors10, Chim C Lang1. 1. Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK. 2. National Heart Centre Singapore, Singapore. 3. Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Amsterdam, The Netherlands. 4. Department of Cardiology (CVK), Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin; Charité Universitätsmedizin Berlin, Berlin, Germany. 5. National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK. 6. University of Bergen, Bergen, Norway. 7. Stavanger University Hospital, Stavanger, Norway. 8. Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. 9. Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Leicester, UK. 10. University Medical Center Groningen, Department of Cardiology, University of Groningen, Groningen, The Netherlands. 11. Inserm CIC-P 1433, Université de Lorraine, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France.
Abstract
AIMS: Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up-titration of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta-blockers on outcome across the age spectrum in HFrEF patients. METHODS AND RESULTS: We analysed HFrEF patients on sub-optimal doses of ACEI/ARB and/or beta-blockers from the BIOSTAT-CHF study stratified by age. Patients underwent a 3-month up-titration period. We used inverse probability weighting to adjust for the likelihood of successful up-titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow-up of 21 months in 1720 HFrEF patients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta-blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI-ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91-0.94, P < 0.001; beta-blocker: HR 0.98, 95% CI 0.95-1.00, P = 0.046], with a significant interaction with age seen for beta-blockers but not ACEI/ARB (P = 0.034 and P = 0.22, respectively). CONCLUSIONS: Achieving higher doses of ACEI/ARB was associated with improved outcome regardless of age. However, achieving higher doses of beta-blockers was only associated with improved outcome in younger, but not in older patients.
AIMS: Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up-titration of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta-blockers on outcome across the age spectrum in HFrEFpatients. METHODS AND RESULTS: We analysed HFrEFpatients on sub-optimal doses of ACEI/ARB and/or beta-blockers from the BIOSTAT-CHF study stratified by age. Patients underwent a 3-month up-titration period. We used inverse probability weighting to adjust for the likelihood of successful up-titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow-up of 21 months in 1720 HFrEFpatients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta-blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI-ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91-0.94, P < 0.001; beta-blocker: HR 0.98, 95% CI 0.95-1.00, P = 0.046], with a significant interaction with age seen for beta-blockers but not ACEI/ARB (P = 0.034 and P = 0.22, respectively). CONCLUSIONS: Achieving higher doses of ACEI/ARB was associated with improved outcome regardless of age. However, achieving higher doses of beta-blockers was only associated with improved outcome in younger, but not in older patients.