Beta Blocker Interruption After Uncomplicated Myocardial Infarction (AβYSS)

• ClinicalTrials.gov Identifier: NCT03498066
• Recruitment Status: Completed
• First Posted: April 13, 2018
• Last Update Posted: December 6, 2023
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Groupe Hospitalier Pitie-Salpetriere
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Myocardial Infarction	Drug: Beta-blockers withdrawal; Drug: Continuation of the Betablockers (βB) treatment	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3700 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of βeta Blocker Interruption After Uncomplicated mYocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization: The AβYSS Study
• Actual Study Start Date: August 29, 2018
• Actual Primary Completion Date: October 31, 2023
• Actual Study Completion Date: October 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Discontinuation of the Betablockers (βB); 1850 post-MI patients treated with chronic βB treatment will undergo withdrawal of their βB treatment..	Drug: Beta-blockers withdrawal; withdrawal of all type of betablockers
Active Comparator: Continuation of the Betablockers (βB); 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; Use Betablockers treatment

Outcome Measures

Primary Outcome Measures :

1. The composite of Major Adverse Cardiovascular Events (MACE) [ Time Frame: Through study completion, with a minimum of 1 year ]

   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.

Secondary Outcome Measures :

1. Quality of life [ Time Frame: Through study completion, with a minimum of 1 year ]
   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.

Other Outcome Measures:

1. Anxiety and Depression [ Time Frame: Through study completion, with a minimum of 1 year ]
   will be evaluated by using the HADS questionnaire to detect the presence of depression and anxiety ( there is no score; this will be determined by the response selected by the patient with "no" = no discomfort to "a lot" = significant discomfort
2. Erection Dysfunction [ Time Frame: Through study completion, with a minimum of 1 year ]
   A precise evaluation of Erectile dysfunction will be proposed to male patients using an internationally validated questionnaire IIEF (International Index of Erectile Function) in French with 5 questions whose answer is graded from 0 to 5 per question
3. Libido [ Time Frame: Through study completion, with a minimum of 1 year ]
   An evaluation of lack of sex drive will be evaluated by answering the following questions about the sexuality of the patient The frequency and degree of sex drive (self evaluation)
4. Exercise Capacity [ Time Frame: Through study completion, with a minimum of 1 year ]

   will be evaluated by answering the following simple questions :

   • The weekly physical activity and the sport practiced
   • Participation in competitions or not additionally, the recording the results of stress tests when available
   • Pre- and post - inclusion stress/ Strain test data
5. Side effects [ Time Frame: Through study completion, with a minimum of 1 year ]
   will be evaluated by answering the following questions: Presence of Blury Vision, Sensation of cold hands and feets, Insomnia and palpitations

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

France

Institut de Cardiologie - USIC - Hôpital Pitié-Salpêtrière

Paris, France, 75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Groupe Hospitalier Pitie-Salpetriere

Investigators

• Study Chair: Johanne SILVAIN, MD-PhD; APHP / Institut de Cardiologie, Pitié-Salpêtrière Hospital, Paris (APHP) / ACTION Study Group / Sorbonne Université Paris-France

More Information

Publications of Results:

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.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT03498066
• Other Study ID Numbers: P150946J
• First Posted: April 13, 2018
• Last Update Posted: December 6, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: There is not a plan to make IPD available

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Myocardial Infarction; Beta-Blockers; Stable Coronary Artery Disease

Additional relevant MeSH terms:

Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs