Beta Blocker Interruption After Uncomplicated Myocardial Infarction (AβYSS)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 4

Conditions: Myocardial Infarction

Treatments: Drug: Continuation of the Betablockers (βB) treatment; Drug: Beta-blockers withdrawal

Study type: Interventional

Funder types: Other

Identifiers

NCT03498066

P150946J

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3,700 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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:

   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 .

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,700 participants in 2 patient groups

Discontinuation of the Betablockers (βB)

Experimental group

Description:

1850 post-MI patients treated with chronic βB treatment will undergo withdrawal of their βB treatment..

Treatment:

Drug: Beta-blockers withdrawal

Continuation of the Betablockers (βB)

Active Comparator group

Description:

1850 post-MI patients treated with chronic βB treatment will be continued under their usual βB treatment without modification.

Treatment:

Drug: Continuation of the Betablockers (βB) treatment