![OUTCOMES
• primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption
group and 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8
percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16
(95% CI, 1.01 to 1.33; P = 0.44 for noninferiority](https://image.slidesharecdn.com/betablockerinterruptionorcontinuationaftermyocardialinfarction-12-240918083051-070f554f/85/BETA-BLOCKER-INTERRUPTION-OR-CONTINUATION-AFTER-MYOCARDIAL-INFARCTION-12-ppt-17-320.jpg)
BETA BLOCKER INTERRUPTION OR CONTINUATION AFTER MYOCARDIAL INFARCTION-12.ppt
- 1. BETA BLOCKER INTERRUPTION OR CONTINUATION AFTER MYOCARDIAL INFARCTION BY M4 UNIT CHIEF:DR.C.BABU ANAND M.D; ASSISTANT PROFESSOR :DR.S.SRIDHAR M.D; DR.P.NIVEDHA M.D; PRESENTOR ;DR.J.INDHUJA
- 2. BACKGROUND • The appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. • Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction.
- 3. ABOUT • This article was published on August 30, 2024, at NEJM.org.
- 4. METHODS (TRIAL DESIGN) • ABYSS was a multicenter, noninferiority trial conducted at 49 sites in France,according to PROBE DESIGN (PROSPECTIVE,RANDOMIZED,OPEN LABEL ,BLINDED END POINT) • Randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. • All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months.
- 5. • The primary end point was • A composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). • The main secondary end point was • change in quality of life as measured by the European Quality of Life–5 Dimensions questionnaire.
- 6. INCLUSION CRITERIA • Subjects meeting all the following criteria will be considered for enrolment into the study: • 1. Male or female ≥ 18 years of age • 2. Current treatment with betablockers whatever the drug or the dose used. • 3. Prior acute myocardial infarction 6 months or more before randomization defined either by: → • 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 o ii) segmental hypoperfusion Thallium or any other imaging technique
- 7. • 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.
- 8. 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 beta-blockers • 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 betablockers
- 9. • 5. Prior episode of ventricular or supraventricular arrhythmia in the past year of follow- up requiring the use of beta-blockers • 6.Treatment with other investigational agents or devices (randomization) 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
- 10. ABYSS TRIAL • ABYSS trial (Assessment of Beta-Blocker Interruption 1 Year after an Uncomplicated Myocardial Infarction on Safety and Symptomatic Cardiac Events Requiring Hospitalization) was conducted to evaluate beta-blocker continuation or interruption among patients with a history of myocardial infarction who had a left ventricular ejection fraction of at least 40%.
- 12. INTERVENTION AND MANAGEMENT • Patients were randomly assigned in a 1:1 ratio to a strategy of either interruption or continuation of beta-blocker therapy with the same agent at the same dose. • Randomization was performed with the use of a centralized system and stratification according to trial center. • Beta-blocker interruption could be tapered if the patient was receiving a high dose of the drug, according to the physician’s preference. • All the patients were evaluated at 6 months and 12 months and then annually after randomization until the last trial entrant had completed the 1-year minimum follow-up
- 13. STATISTICAL ANALYSIS • Enrollment of 3700 patients would provide the trial • 1846 to the interruption group and 1852 to the continuation group . • The mean (±SD) age of the patients was 63.5±11 years, and 17.2% were women.
- 15. • Median resting heart rate during the randomization visit was 63 beats per minute (interquartile range, 57 to 71). • Patients were followed for a median of 3.0 years
- 16. END POINTS • The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for any other cardiovascular reason. • The main secondary end point was the change in score from baseline to 6 months and 12 months on the European Quality of Life–5 Dimensions (EQ-5D) questionnaire • (with scores ranging from 0 to 1, and higher scores indicating better health status; minimal clinically important difference, 0.05 points).
- 17. OUTCOMES • primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P = 0.44 for noninferiority
- 19. SECONDARY END POINTS • The composite end point of death, myocardial infarction, or stroke occurred in 132 patients (7.2%) in the interruption group and 126 patients (6.8%) in the continuation group. • The composite end point of death, myocardial infarction, stroke, or hospitalization for heart failure occurred in 155 patients (8.4%) in the interruption group and 141 patients (7.6%) in the continuation group
- 20. KAPLAN MEYER CURVE risk of the primary cardiovascular end point was 21.8% in the interruption group and 19.3% in the continuation group
- 21. risk of death, myocardial infarction, or stroke was 9.0% and 8.4%, respectively
- 22. risk of death, myocardial infarction, stroke, or hospitalization for heart failure was 10.0% and 8.9%, respectively; and the risk of death from any cause was 6.1% and 5.9%,
- 23. • In our trial, we tested the hypothesis that the interruption of beta-blocker therapy would be noninferior to the continuation of such therapy over a 3-year follow-up period among patients with a history of myocardial infarction. • However, the noninferiority of this strategy was not shown with respect to the risk of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons (the composite primary outcome). • In addition, interruption of beta-blocker therapy did not result in an improvement in patient-reported quality of life.
- 24. • Beta-blocker interruption was associated with a numerical increase in the risk of recurrent angina and other coronary-related conditions leading to hospitalization and coronary procedures, although hypothesis testing was not performed for these end points
- 25. CONCLUSION • In our study Interruption of long-term beta-blocker treatment in patients with a history of myocardial infarction was not shown to be noninferior to a strategy of beta-blocker continuation with respect to a composite outcome of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons, nor did it seem to improve the patients’ quality of life.
- 26. LIMITATIONS • First, the trial was not blinded, which may have influenced several outcomes, including evaluation of quality of life. • Second, we anticipated that in daily practice patients who have a history of myocardial infarction would be treated with less-than-effective doses of beta-blockers, as suggested in previous reports, but the baseline heart rate of our patients seems to indicate appropriate use of beta blocker. • Third, the trial was conducted within a single country, so results may not be generalizable to other health care systems with different practices.
- 27. • However, the main difference with our results is that we found an increase in hospitalization for cardiovascular reasons with beta-blocker interruption, an end point that was not evaluated in REDUCE-AMI.(Randomized Evaluation of Decreased Usage of Beta blockers after acute MI) • Other trials that are evaluating the superiority of beta-blockers after an uncomplicated myocardial infarction with preserved left ventricular ejection fraction are ongoing.
- 28. BETA BLOCKERS Three types of Beta-receptors ( 1, 2, 3) β β β • 1 β receptors : Heart • 2 β receptors :Vascular and bronchial smooth muscle • 3 β receptors : Adipocytes
- 29. BETA RECEPTORS AND ITS EFFECT
- 31. • Vasodilation is due to • Direct vasodilation via nitric oxide (carvedilol,nebivolol) • receptor blockade (labetalol, carvedilol) α • Carvedilol is also antiproliferative, antioxidant and blocks the expression of several genes involved in myocardial damage
- 32. CLASSIFICATION OF BETA BLOCKERS • Depending on their level of affinity for B-receptors. • Selective -blockers : affinity -1> -2 : selectivity lost at higher doses β β β • Atenolol • Bisoprolol • Celiprolol • Metoprolol • Nebivolol • Non-selective -blockers : affinity 1 = 2- β β β • Carvedilol • Labetalol • Propranolol • Sotalol
- 33. BETA 1VS BETA 2 SELECTIVITY
- 34. SUMMARY OF USE OF BETA BLOCKERS IN CARDIOVASCULAR DISEASES
- 35. ACTIONS OF BETA BLOCKERS
- 38. MECHANISM OF BETA BLOCKERS IN HEART FAILURE • Upregulation of receptors and improved adrenergic signaling. β β • Reducing the hyperphosphorylation of calcium release channels of sarcoplasmic reticulum and normalizing their function • Bradycardia ( coronary blood flow and decreased myocardial oxygen demand). ↑ • Protection from catecholamine myocyte toxicity. • Suppression of ventricular arrhythmias. • Anti-apoptosis. 2 receptors, which are relatively increased, are coupled to inhibitory G protein & block β apoptosis. • Inhibition of RAAS.When added to prior ACE-I or ARB, metoprolol augments RAAS inhibitors
- 39. PHARMACOLOGY • Pharmacology • Bisoprolol is a highly potent ß1 adrenoceptor blocking agent • No ISA • No pronounced negative inotropic effects • Low affinity for ß2-receptors involved with metabolic regulation • does not influence airways resistance • no adverse changes in lipid profile • no adverse changes in blood glucose levels • Maximal antihypertensive effect reached in 2 weeks
- 40. ELIMINATION ROUTES OFVARIOUS BETA BLOCKERS FROM BODY
- 41. THANKYOU
- 42. • Other secondary end points were a composite of death, nonfatal myocardial infarction, or nonfatal stroke and a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.