Comparison of Bisoprolol and Carvedilol in elderly heart failure (HF) patients: a randomised, double-blind multicentre study

Conditions

Chronic heart failure Circulatory System Heart failure

Edelmann F, Musial-Bright L, Gelbrich G, Trippel T, Radenovic S, Wachter R, Inkrot S, Loncar G, Tahirovic E, Celic V, Veskovic J, Zdravkovic M, Lainscak M, Apostolović S, Neskovic AN, Pieske B, Düngen HD, CIBIS-ELD Investigators and Project Multicenter Trials in the Competence Network Heart Failure.

2015-12-0950 citations

10.1016/j.jchf.2015.10.008

Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.

Düngen HD, Apostolovic S, Inkrot S, Tahirovic E, Töpper A, Mehrhof F, Prettin C, Putnikovic B, Neskovic AN, Krotin M, Sakac D, Lainscak M, Edelmann F, Wachter R, Rau T, Eschenhagen T, Doehner W, Anker SD, Waagstein F, Herrmann-Lingen C, Gelbrich G, Dietz R, CIBIS-ELD investigators and Project Multicentre Trials in the Competence Network Heart Failure.

2011-03-23137 citations

10.1093/eurjhf/hfr020

Interventions

Current intervention as of 15/01/2008: Double-blind (bisoprolol versus carvedilol) tolerance-guided beta-blocker titration. Dosages of study drugs: The target dose for bisoprolol was set at 10 mg/d,

in the bisoprolol group the increment is only technically treated like a dose increase for blinding purposes. The highest tolerated dose increment is maintained until the primary endpoint is reached (

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Current inclusion criteria as of 15/01/2008: 1. Age greater than or equal to 65 years 2. Current diagnosis of chronic heart failure from New York Heart Association (NYHA) II - IV or ejection fraction (EF) less than 40% 3. Clinically stable heart failure for 2 weeks before inclusion 4. Informed consent Previous inclusion criteria: 1. Age greater than or equal to 65 years 2. Chronic heart failure New York Heart Association (NYHA) II - IV or ejection fraction (EF) less than 40% 3. Clinically stable heart failure for 2 weeks before inclusion 4. Informed consent given

Exclusion criteria

Exclusion criteria: Current exclusion criteria as of 15/01/2008: Most relevant exclusion criteria: 1. Acute/decompensated HF 2. Shock, pulmonary embolism 3. Obstructive/restrictive cardiomyopathy 4. Severe pulmonary disorders/asthma 5. Inflammatory heart diseases 6. Standard exclusion criteria (as listed in the protocol) 7. Contraindications against beta blockers (as listed in the protocol) 8. Restricted concomittant medication (as listed in the protocol) Previous exclusion criteria: Most relevant exclusion criteria: 1. Acute/decompensated HF 2. Shock, pulmonary embolism 3. Obstructive/restrictive cardiomyopathy 4. Severe pulmonary disorders/asthma 5. HTN not controlled 6. Inflammatory heart diseases 7. Standard exclusion criteria (as listed in the protocol) 8. Contraindications against beta blockers (as listed in the protocol) 9. Restricted concomittant medication (as listed in the protocol)

Design outcomes

Primary

Measure	Time frame
Current primary outcome measures as of 15/01/2008: Tolerance (yes/no) of the study medication target dose as per cardiology guidelines. Tolerance (= yes) is defined when: 1. Dose titration was possible up to the target dose 2. The study medication dose was not reduced. It is irrelevant whether unscheduled T-visits took place if the titration aim was not affected 3. The target dose is to be taken at the time of last visit. This dose has remained stable for at least 10 days. Tolerance is ascertained (i.e. there is no reason for dose reduction and the patient did not reduce it independently either) Previous primary outcome measures: Tolerability, measured as individually achieved dose at end of titration.	—

Measure

Time frame

Current primary outcome measures as of 15/01/2008: Tolerance (yes/no) of the study medication target dose as per cardiology guidelines. Tolerance (= yes) is defined when: 1. Dose titration was possible up to the target dose 2. The study medication dose was not reduced. It is irrelevant whether unscheduled T-visits took place if the titration aim was not affected 3. The target dose is to be taken at the time of last visit. This dose has remained stable for at least 10 days. Tolerance is ascertained (i.e. there is no reason for dose reduction and the patient did not reduce it independently either) Previous primary outcome measures: Tolerability, measured as individually achieved dose at end of titration.

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Secondary

Measure	Time frame
Current secondary outcome measures as of 15/01/2008: Correlation between the medication and the following secondary endpoints: 1. Time to treatment failure (TTF) 2. Dose increment attained (% of maximum) for long term treatment 3. Number of adverse events (AE) or serious adverse events (SAE) in total as well as itemised according to their relation to dose reduction/ discontinuation of treatment 4. Lung function (vital capacity [VC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF] and maximal mid-expiratory flow [MEF50]) 5. NYHA class 6. 6-minute walk test 7. Diastolic function (according to the American Society of Echocardiography [ASE]) and left ventricular function (fractional shortening and EF according to Simpson [looking at four chambers] from echocardiography before and after beta-blocker titration) 8. Quality of life, depression and physical well-being (measured with the following instruments: 36-item short form health survey [SF-36], Patient Health Questionnaire [PHQ-D] and KWB-16) 9. Heart rate at rest and under stress 10. Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and BNP concentration 11. Alteration of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides plasma concentration 12. Investigation of parameters for the current medical treatment of HF patients = 65 years old: 13. Frequency of beta-blocker, diuretic, angiotensin converting enzyme (ACE)-inhibitor or angiotensin receptor antagonist prescription 14. Qualitative and quantitative survey of other therapeutic actions 15. Hospitalisations 16. Days alive and days out of hospital Previous secondary outcome measures: 1. Survey on current drug therapy in heart failure patients greater than or equal to 65 years 2. Number of adverse events (AE's) 3. Changes during titration phase in: 3.1. Lung function parameters 3.2. NYHA class/EF 3.3. 6-minute walki	—

Measure

Time frame

Current secondary outcome measures as of 15/01/2008: Correlation between the medication and the following secondary endpoints: 1. Time to treatment failure (TTF) 2. Dose increment attained (% of maximum) for long term treatment 3. Number of adverse events (AE) or serious adverse events (SAE) in total as well as itemised according to their relation to dose reduction/ discontinuation of treatment 4. Lung function (vital capacity [VC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF] and maximal mid-expiratory flow [MEF50]) 5. NYHA class 6. 6-minute walk test 7. Diastolic function (according to the American Society of Echocardiography [ASE]) and left ventricular function (fractional shortening and EF according to Simpson [looking at four chambers] from echocardiography before and after beta-blocker titration) 8. Quality of life, depression and physical well-being (measured with the following instruments: 36-item short form health survey [SF-36], Patient Health Questionnaire [PHQ-D] and KWB-16) 9. Heart rate at rest and under stress 10. Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and BNP concentration 11. Alteration of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglycerides plasma concentration 12. Investigation of parameters for the current medical treatment of HF patients = 65 years old: 13. Frequency of beta-blocker, diuretic, angiotensin converting enzyme (ACE)-inhibitor or angiotensin receptor antagonist prescription 14. Qualitative and quantitative survey of other therapeutic actions 15. Hospitalisations 16. Days alive and days out of hospital Previous secondary outcome measures: 1. Survey on current drug therapy in heart failure patients greater than or equal to 65 years 2. Number of adverse events (AE's) 3. Changes during titration phase in: 3.1. Lung function parameters 3.2. NYHA class/EF 3.3. 6-minute walki

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Countries

Germany, Montenegro, Serbia, Slovenia

Outcome results

None listed