Short summary

DANBLOCK is a randomized controlled trial testing the benefits of long-term betablocker therapy in patients with myocardial infarction with preserved ejection fraction and no signs of heart failure. A total of 2760 patients will be randomized to betablocker therapy or no such therapy. The aim of the study is to determine whether betablocker therapy reduces a composite outcome of death, stroke, myocardial infarction, heart failure, revascularization, ventricular arrhytmia, or cardiac arrest.

Rationale

Betablockade has been a cornerstone in the treatment after acute myocardial infarction for decades. Most trials testing the effect of betablocker in myocardial infarction were conducted before reperfusion was standard treatment and before efficient secondary prevention with statins and antiplatelet agents reduced case-fatality. In contemporary post myocardial infarction patients, the ischemic substrate is small, risk of arrhythmias reduced and the outlook much improved. A meta-analysis of randomized trials that compared effect of betablocker treatment in pre- and reperfusion era concluded that the reduction in mortality with betablocker treatment was only documented in the pre-reperfusion era. In a meta-analysis of more recent trials and observational studies including only patients with acute myocardial infarction who underwent primary coronary intervention, all-cause mortality was not significantly reduced in patients with preserved pumping function of the heart. Long-term betablocker treatment has furthermore not been investigated in patients with non-ST-segment elevation myocardial infarction and preserved pumping function of the heart. A continued role of betablockers after myocardial infarction with preserved pumping function of the heart is therefore called into question.

Despite wide-spread use and tolerability, side-effects of betablockers are well-known and common. They include depressive symptoms, sexual dysfunction, vivid dreams, cold hands and feet, weight gain and fatigue. Betablockers also reduce maximal heart rate and recent evidence indicates that patients treated with betablockers have lower maximal exercise capacity, an indicator of daily function capacity and a strong prognostic marker. On the other hand, betablockertreatment reduces angina symptoms, which has profound effects on quality of life. Thus, the benefit of betablockertreatment on survival outlook needs to be weighed against the impact on side-effects as well as quality of life, which is a secondary endpoint to this study. 

Description of the cohort

A total of 2760 patients with a history of acute myocardial infarction within the past 14 days and preserved ejection fraction will be recruited and randomized 1:1 to betablocker treatment or no betablocker treatment. All departments of cardiology in Denmark are invited to participate. At study end data from DANBLOCK will be combined with a similar study from Norway called BETAMI and the main results will be published together. 

Data and biological material

The primary and safety endpoints will be obtained through individual-level linkage between data obtained at inclusion and nationwide administrative registries. Assessment of secondary registry-based study endpoints will be through administrative registries, clinical registries on cardiac rehabilitation and e-questionnaires for patient related outcomes. The following e-questionnaires will be used: 

• Measures for quality of life: EQ5D
• Measures of depression and anxiety: HADS (Hospital Anxiety and Depression Scale)

Measures of sexual dysfunction one year after MI: Short versions of IIEF (The International Index of Erectile Function) and FSFI (Female Sexual Function Index)

• Measures of sleeping disorder: Bergen Insomnia Scale
• Angina burden following MI: NYHA (New York Heart Association); CCS (Canadian Cardiovascular Society grading of angina pectoris); Seattle Angina questionnaire (SAQ). 

Collaborating researchers and departments

Department of Cardiology, Bispebjerg Hospital

• Professor and PI Eva Prescott, MD, DMSc
• Project manager Thomas Sehested, MD
• Ass Project manager Anna Meta Dyrvig Kristensen, Stud.med.
• Head of Department Ida Gustafsson, MD, PhD,

Department of Cardiology, Holbæk sygehus 

• Professor Michael Hecht Olesen, MD, PhD

Danish Centre for Rehabilitation and Palliative Care, Odense University Hospital and University of Southern Denmark 

• Professor Ann Dorthe Zwisler, MD, PhD, 

Department of Cardiology, Aalborg University Hospital 

• Ass Professor Svend Eggert Jensen
• Professor Mogens Lytken Larsen, MD, DMSc

Department of Cardiology, Esbjerg Hospital 

• Consultant Kristian Korsgaard Thomsen, MD, PhD

Department of Cardiology, Regional Hospital West Jutland

• Consultant Ann Bovin, MD, PhD

Department of Cardiology, Aarhus University Hospital 

• Professor Hans Erik Bøtker, MD, DMSc

Frederiksberg Heart Clinic

• Per Hildebrandt, MD, DMSc

Department of Cardiology, Odense University Hospital

• Consultant Karsten Veien, MD, PhD

Ålborg University Hospital, Department of Health Science and Technology 

• Professor Christian Torp-Pedersen, MD, DMSc

Hvidovre Amager Hospital, Representative of Cardiac Rehabilitation Nursing

• Nurse Sussie Foghmar

Department Manager, The regional clinical quality development program

• Charlotte Cerquira, MD, PhD

Department of Biostatistics, University of Copenhagen

• Theis Lange, biostatistician

Publications associated with the project

Design and rationale of the Danish trial of beta-blocker treatment after myocardial infarction without reduced ejection fraction: study protocol for a randomized controlled trial

The Danish-Norwegian randomized trial on beta-blocker therapy after myocardial infarction: Design, rationale, and baseline characteristics