Background
Randomized controlled trials evaluating beta-blocker therapy
Evidence from meta-analyses of observational studies
Guideline recommendations
Compliance and side effects
Objectives
Methods/design
Trial design
Eligibility criteria
Inclusion criteria | |
• Myocardial infarction within 14 days according to the Universal ESC definition of MI: Detection of a rise and/or fall of cardiac biomarker values with at least one value above the 99th percentile upper reference limit and with at least one of the following: | |
• Symptoms of ischemia | |
• New or presumed new significant ST-segment–T wave changes or new left bundle branch block | |
• Development of pathological Q waves in the ECG | |
• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality | |
• Age > 18 years | |
• LVEF > 40% by any imaging technique during hospitalization | |
Exclusion criteria | |
• Any condition that requires beta-blocker treatment according to the treating physician, including but not limited to: | |
• Beta-blocker-treated arrhythmias | |
• Beta-blocker-treated hypertension | |
• Reduced left ventricular ejection fraction | |
• Cardiomyopathies | |
• Any condition in which beta-blocker treatment is contraindicated according to the treating physician, including but not limited to: | |
• Hypotension | |
• Brady-arrhythmias | |
• Severe peripheral artery disease | |
• History of not able to tolerate beta-blocker therapy | |
• Severe chronic obstructive pulmonary disease or asthma | |
• Severe valvular heart disease | |
• Any condition (i.e., dementia) that could lead to increased risk for the patient when treated with beta-blockers | |
• Clinical evidence of heart failure at the time of randomization | |
• Lack of signed informed consent and expected cooperation during follow-up | |
• Pregnancy or of child bearing age not using safe contraception throughout the study period |
Medical treatment and adherence
Data collection and study endpoints
Primary endpoints and their rationale
Secondary endpoints and their rationale
Primary endpoints | |
• A composite of all-cause mortality and hospitalization for recurrent non-fatal myocardial infarction, unstable angina pectoris, stroke, or acute decompensated heart failure | |
Secondary endpoints | |
• Each of the components of the primary outcome | |
• Cardiovascular mortality | |
• Atrial fibrillation and atrial flutter | |
• Cardiac arrest | |
• Ventricular arrhythmias | |
• Stable angina pectoris | |
• Bradycardia, syncope, or need for pacemaker | |
• Hospitalization for asthma and chronic obstructive pulmonary disorder | |
• Hospitalization for diabetes (new onset and dysregulation) | |
• Hospitalization for dysregulated blood pressure | |
• Peripheral artery disease | |
• Blood pressure controla | |
• Exercise capacitya | |
Patient reported outcomes (PRO) regarding: | |
• Health-related quality of life, depression, sexual dysfunction, angina burden following MI, and sleep disorders |
Time and assessment | Enrolment | Treatment period following randomization | Study end | |||
---|---|---|---|---|---|---|
At randomization | Every 3 months | 3 months | 1 year | 2 year | ||
Eligibility screen, informed consent, allocation to treatment group, and collection of baseline dataa | x | |||||
Self-reported questionnaires on quality of life and symptom burdenb | x | x | x | x | ||
Risk factor control and benefit from cardiac rehabilitationc | x | |||||
Adherence to treatment groupd | x | x | ||||
Information on hospital admissionse | x | x | ||||
Endpoints from registry data | x |
Study organization, safety, and monitoring
Patient and public involvement
Ongoing beta-blocker trials
DANBLOCK | REDUCE-SWEDEHEART | BETAMI | |
---|---|---|---|
Inclusion criteria | |||
Age | ≥ 18 years | ≥ 18 years | ≥ 18 years |
MI definition | The universal definition of MI | The universal definition of MI (type 1) | The universal definition of MI (type 1) |
Randomized prior to | Day 14 after MI | Day 7 after MI | Not specified |
Revascularization | No criteria for revascularization | Obstructive coronary artery disease documented by coronary angiography | PCI or thrombolysis during hospitalization |
LVEF cutoff value | > 40% | ≥ 50% | ≥ 40% |
Exclusion criteria | Any medical condition where beta-blocker therapy is indicated or contraindicated according to the treating physician | Any medical condition where beta-blocker therapy is indicated or contraindicated according to the treating physician | Any medical condition where beta-blocker therapy is indicated or contraindicated according to the treating physician |
Primary endpoints | A composite of all-cause mortality and hospitalization for recurrent non-fatal MI, unstable angina pectoris, stroke, and acute decompensated heart failure | Time to the composite of death of any cause or MI | Time to the composite of all cause mortality or non-fatal MI |
Expected number of randomized patients | 3570 | 7000 | 10,000 |
Expected number of events | 900 | 944 | 794 |
Expected number of events to contribute to a pooled meta-analysis | 632 | 944 | 794 |
Individual study power if true HR was 1.2 | 0.619 | 0.797 | 0.732 |