Beta Blocker Interruption After Uncomplicated Myocardial Infarction

Study Overview
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Brief Summary
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ABYSS is a national, multicenter, randomised, open label trial using the PROBE study design, that will evaluate the non-inferiority of the interruption of ΒB therapy after an uncomplicated MI after six months or more of follow-up compared to the continuation of βB evaluated by the primary endpoint or death, MI, Stroke and rehospitalization for others cardiovascular reasons.

Detailed Description
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Despite the outstanding progress made in cardiac care over the last few years, cardiovascular diseases remain the leading cause of morbidity and mortality in developed countries. After the initial clinical event, patients are considered to have a chronic disease which combined with the increasing actual life expectancy patients with CAD are a major source of expenses due to their life-long treatment and follow-up. ΒB are prescribed during the initial hospitalisation for MI and in the post-MI phase. European (European Society of Cardiology, ESC) and American (ACC/AHA) guidelines initially gave βB therapy a class I recommendation for MI or acute coronary syndrome (ACS) for the first year of treatment and extended such recommendation without solid data up to 3 years after MI , . However, there has been no recent clinical trial to evaluate safety and efficacy of long term ΒB therapy in the contemporary therapeutic era. Taking such lack of evidence in account and acknowledging that clinical practice has changed, the latest ESC STEMI (2014) and NSTEMI (2015) Guidelines degraded the recommendation for the use of ΒB in post MI patients (Class IIa B) during the hospitalization period and they question the validity of its use after the initial stabilization phase. This was confirmed in the 2017 STEMI Guidelines. The primary objective of the ABYSS trial is to demonstrate the non-inferiority of the interruption of ΒB therapy after an uncomplicated MI after six months or more of follow-up compared to the continuation of βB evaluated by the primary endpoint. The primary endpoint of the study will be evaluated, with one-year minimum follow-up, and will be the composite of Major Adverse Cardiovascular Events (MACE) measured at the longest follow-up including: All-cause death Stroke Myocardial infarction Hospitalisation for other cardiovascular (CV) reason. It is expected that the interruption of βB therapy will not alter the prognosis of patients and improve safety and quality of life of patients and considerably reduce healthcare direct or indirect costs.

Official Title
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Assessment of βeta Blocker Interruption After Uncomplicated mYocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization: The AβYSS Study

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Beta-blockers withdrawal
* Drug: Continuation of the Betablockers (βB) treatment


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Subjects meeting all of the following criteria will be considered for enrolment into the study: Male or female +/=18 years of age Current treatment with βB whatever the drug or the dose used Prior acute myocardial infarction 6 months or more before randomisation defined either by: AβYSS protocol, version 3.0 of 25/05/2021 Page 32 / 65 An episode of ST elevation MI with ST segment elevation (STEMI) and/or the presence of Q wave (Type I MI) an episode of Non ST Elevation MI (NSTEMI) with preferably at least one of the followings: i) a documented hypokinetic or akinetic segment on echo or any other imaging technique ii) segmental hypoperfusion Thallium or any other imaging technique iii) segmental aspect of necrosis on MRI An episode of silent MI discovered on ECG or Cardiac Imaging. Importantly = The mention of an MI on a report is enough to be considered as a prior MI and it is not necessary to retrieve the source document and/or documentation of this prior MI . Patient affiliated to Social Security Informed consent obtained in writing at enrolment into the study Exclusion Criteria: Subjects presenting with any of the following will not be included in the study: Uncontrolled arterial hypertension according to investigator decision Prior episode of heart failure in the past two years of follow-up and/or low left ventricular ejection fraction <40% requiring the use of βB; New ACS (in the past 6 months) including UA/NSTEMI and STEMI; Persistent angina or ischemia (>10% viable myocardium) requiring the use of βB; Prior episode of ventricular or supraventricular arrhythmia in the past year of follow-up requiring the use of ΒB; Treatment with other investigational agents or devices within the previous 30 days, or previous enrolment in this trial. Pregnant Women or breast feeding women Patient under legal protection (protection of the court, or in curatorship or guardianship).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Discontinuation of the Betablockers (βB)<br>1850 post-MI patients treated with chronic βB treatment will undergo withdrawal of their βB treatment.. | Drug: Beta-blockers withdrawal<br>* withdrawal of all type of betablockers<br>|
| Active Comparator: Continuation of the Betablockers (βB)<br>1850 post-MI patients treated with chronic βB treatment will be continued under their usual βB treatment without modification. | Drug: Continuation of the Betablockers (βB) treatment<br>* Use Betablockers treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The composite of Major Adverse Cardiovascular Events (MACE) | Will be evaluated with one-year minimum follow-up and will be the composite of Major Adverse Cardiovascular Events (MACE) including: All-cause death Myocardial infarction (MI) Stroke Hospitalisation for any cardiovascular (CV) reason. | Through study completion, with a minimum of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life | will be evaluated by the questionnaire EQ5D-5L Score (0 to 1) and EQ5D-5L Scale (0 to 100) with higher scores indicating a better quality of Life. | Through study completion, with a minimum of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial Infarction, Beta-Blockers, Stable Coronary Artery Disease