Clinical trial NCT03498066: Beta Blocker Interruption After Uncomplicated Myocardial Infarction
Official title: Assessment of βeta Blocker Interruption After Uncomplicated mYocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization: The AβYSS Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: Myocardial Infarction
Beta-Blockers
Stable Coronary Artery Disease
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Groupe Hospitalier Pitie-Salpetriere
First posted: 2018-04-13
Enrollment: 3700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion criteria

Subjects meeting all of the following criteria will be considered for enrolment into the study:

1. Male or female +/=18 years of age
2. Current treatment with βB whatever the drug or the dose used
3. Prior acute myocardial infarction 6 months or more before randomisation defined either by:

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   * 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 .
4. Patient affiliated to Social Security
5. 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:

  1. Uncontrolled arterial hypertension according to investigator decision
  2. 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;
  3. New ACS (in the past 6 months) including UA/NSTEMI and STEMI;
  4. Persistent angina or ischemia (\>10% viable myocardium) requiring the use of βB;
  5. Prior episode of ventricular or supraventricular arrhythmia in the past year of follow-up requiring the use of ΒB;
  6. Treatment with other investigational agents or devices within the previous 30 days, or previous enrolment in this trial.
  7. Pregnant Women or breast feeding women
  8. Patient under legal protection (protection of the court, or in curatorship or guardianship).

Primary outcomes:
measure: The composite of Major Adverse Cardiovascular Events (MACE)
timeFrame: Through study completion, with a minimum of 1 year
Secondary outcomes:
measure: Quality of life
timeFrame: Through study completion, with a minimum of 1 year
Other outcomes:
measure: Anxiety and Depression
timeFrame: Through study completion, with a minimum of 1 year
measure: Erection Dysfunction
timeFrame: Through study completion, with a minimum of 1 year
measure: Libido
timeFrame: Through study completion, with a minimum of 1 year
measure: Exercise Capacity
timeFrame: Through study completion, with a minimum of 1 year
measure: Side effects
timeFrame: Through study completion, with a minimum of 1 year
Locations:
city: Paris
country: France
facility: Institut de Cardiologie - USIC - Hôpital Pitié-Salpêtrière
Study officials:
affiliation: APHP / Institut de Cardiologie, Pitié-Salpêtrière Hospital, Paris (APHP) / ACTION Study Group / Sorbonne Université Paris-France
name: Johanne SILVAIN, MD-PhD
role: STUDY_CHAIR
References:
citation: Silvain J, Cayla G, Ferrari E, Range G, Puymirat E, Delarche N, Collet JP, Dumaine R, Slama M, Payot L, Kasty ME, Aacha K, Vicaut E, Montalescot G; ABYSS investigators of the ACTION Study Group,. betaeta blocker interruption after uncomplicated myocardial infarction: rationale and design of the randomized ABYSS trial. Am Heart J. 2023 Apr;258:168-176. doi: 10.1016/j.ahj.2023.01.014. Epub 2023 Jan 20.