BETA BLOCKERS

DR. VIKAS MEDEP

DEPT.OF CARDIOLOGY

NIMS

TOPIC LAYOUT

INTRODUCTIONINTRODUCTION PHYSIOLOGYPHYSIOLOGY CLASSIFICATIONCLASSIFICATION MECHANISM OF ACTIONMECHANISM OF ACTION INDICATIONSINDICATIONS HEART DISEASESHEART DISEASES CONTRA-INDICATIONS.CONTRA-INDICATIONS.

HISTORY AND IMPORTANCE

Beta-blockers were first developed by Sir James black in Beta-blockers were first developed by Sir James black in the UK in 1962 was awarded the Nobel prize in 1988.the UK in 1962 was awarded the Nobel prize in 1988.

Beta-blockers are one of the 4 oral medications proven Beta-blockers are one of the 4 oral medications proven to decrease CV morbidity and mortality. to decrease CV morbidity and mortality.

The other three agents being AcE-inhibitors, antiplatelets The other three agents being AcE-inhibitors, antiplatelets and statins.and statins.

The approximate life-saving potential of these agentsThe approximate life-saving potential of these agents Beta-blockers 33%, Aspirin 23%, AcE inhibitors 20% and Beta-blockers 33%, Aspirin 23%, AcE inhibitors 20% and

Statins 15%.Statins 15%. More than 100 beta-blockers have been developed, only More than 100 beta-blockers have been developed, only

about 30 are available for clinical useabout 30 are available for clinical use

SOLUABILITY Water-soluble beta-blockers (Atenolol, Nadolol) tend to Water-soluble beta-blockers (Atenolol, Nadolol) tend to

have longer half-lives and are eliminated via the kidney. have longer half-lives and are eliminated via the kidney. Lipid-soluble beta-blockers (metoprolol, propranolol) are Lipid-soluble beta-blockers (metoprolol, propranolol) are

metabolized mainly in the liver and have shorter half-metabolized mainly in the liver and have shorter half-lives.lives.

DURATION OF ACTION Short action – eg EsmololShort action – eg Esmolol Long acting – eg PropranololLong acting – eg Propranolol

GENERATIONS

INDICATIONS

HEART FAILURE

Beta-blockers are now the cornerstone of systolic heart Beta-blockers are now the cornerstone of systolic heart failure therapy.failure therapy.

Beta-blocker use is associated with a 30% reduction in Beta-blocker use is associated with a 30% reduction in mortality, 40% reduction in hospitalizations and 38% mortality, 40% reduction in hospitalizations and 38% reduction in sudden death in patients with chronic heart reduction in sudden death in patients with chronic heart failure.*failure.*

Carvedilol, Metoprolol succinate XL, Bisoprolol and Nebivolol.Carvedilol, Metoprolol succinate XL, Bisoprolol and Nebivolol.

Brophy JM, Joseph L, Rouleau JL. Beta-blockers in congestive heart failure. A Bayesian meta-analysis. Ann Intern Med 2001; 134:550.

EuropeanHeartJournal(1996 )1 7(SupplementB),17-20

ACUTE MYOCARDIAL INFARCTION

Beta blockers significantly reduce morbidity and mortality Beta blockers significantly reduce morbidity and mortality in patients with acute MIin patients with acute MI

Upto 40% reduction in mortality, beta-blockers reduce Upto 40% reduction in mortality, beta-blockers reduce the odds of death by 23%.*the odds of death by 23%.*

Current recommendations are to avoid early (<24 hr) Current recommendations are to avoid early (<24 hr) beta-blocker use in patients with hemodynamic beta-blocker use in patients with hemodynamic instability, or risk of cardiogenic shock (age > 70 yrs, instability, or risk of cardiogenic shock (age > 70 yrs, systolic blood pressure <120 mmHg, heart rate >110 systolic blood pressure <120 mmHg, heart rate >110 bpm, killip class III on presentation). bpm, killip class III on presentation).

*( Yusuf S et al, 1985 & ISIS-1 TRIAL 1986)*( Yusuf S et al, 1985 & ISIS-1 TRIAL 1986)

MECHANISM Decreased oxygen demand due to the reductions in Decreased oxygen demand due to the reductions in

heart rate, blood pressure, and contractility, and the heart rate, blood pressure, and contractility, and the consequent relief of ischemic chest pain.consequent relief of ischemic chest pain.

Decreased risk of VF ,a relative risk reduction in sudden Decreased risk of VF ,a relative risk reduction in sudden cardiac deathcardiac death

Decreased automaticity, increased electrophysiologic Decreased automaticity, increased electrophysiologic

threshold for activation, and slowing of conductionthreshold for activation, and slowing of conduction..

Bradycardia prolongs diastole and therefore improves Bradycardia prolongs diastole and therefore improves coronary diastolic perfusion and reduces coronary diastolic perfusion and reduces afterdepolarizations and triggered activity.afterdepolarizations and triggered activity.

Reduction in remodeling and improvement in left Reduction in remodeling and improvement in left

ventricular hemodynamic functionventricular hemodynamic function,,

POST MYOCARDIAL INFARCTION PROTECTION

Beta-blocker use in Post MI patients reduces CV events Beta-blocker use in Post MI patients reduces CV events by 23% in prospective studies and upto 40% in by 23% in prospective studies and upto 40% in observational studies.*observational studies.*

The benefits are greatest in patients at high risk The benefits are greatest in patients at high risk (advanced age, LV dysfunction, large anterior infarction, (advanced age, LV dysfunction, large anterior infarction, complex ventricular ectopy). complex ventricular ectopy).

In fact, the only medications proven to reduce SCD in In fact, the only medications proven to reduce SCD in

Post MI patients are beta blockers.Post MI patients are beta blockers.

*( Freemantle et al 1999; Worcester Heart Attack Study 2003)*( Freemantle et al 1999; Worcester Heart Attack Study 2003)

β-Blockers in the Post−Myocardial Infarction Patient, Mihai Gheorghiade and Sidney Goldstein, Circulation. 2002;106:394-398

Anti-arrhythmic Effects

Mechanisms: beta-blockers negate the arrhythmogenic : beta-blockers negate the arrhythmogenic influence of excessive catecholamine states. influence of excessive catecholamine states.

I cal and I f ionic currents are inhibited at the level of I cal and I f ionic currents are inhibited at the level of action potentials. (class II effect). action potentials. (class II effect).

Sotalol, specifically, prolongs APd (class III anti-Sotalol, specifically, prolongs APd (class III anti-arrhythmic effect). arrhythmic effect).

Membrane stabilization effect (class I effect) is usually Membrane stabilization effect (class I effect) is usually not seen at the therapeutic dosages of beta blockers not seen at the therapeutic dosages of beta blockers employedemployed

Efficacy & clinical use: : In post-MI patients, beta-blockers are superior to

other anti-arrhythmics for ventricular tachyarrhythmias and reduce arrhythmic cardiac deaths..

The ESVEM study showed that sotalol was more The ESVEM study showed that sotalol was more effective than a variety of class I anti-arrhythmics for effective than a variety of class I anti-arrhythmics for ventricular tachyarrhythmias in post MI patients. ventricular tachyarrhythmias in post MI patients.

Beta-blockers can slow, terminate or prevent Beta-blockers can slow, terminate or prevent supraventricular tachycardias (SVTs)supraventricular tachycardias (SVTs)

Inherited Arrhythmogenic disorders

Beta-blockers are recommended for patients with a Beta-blockers are recommended for patients with a clinical diagnosis of Long QT syndrome 1 (LQTS 1). clinical diagnosis of Long QT syndrome 1 (LQTS 1).

ICD+ beta blockers are recommended for patients with ICD+ beta blockers are recommended for patients with LQTS and h/o resuscitated cardiac arrest LQTS and h/o resuscitated cardiac arrest

Beta-blockers are also the drugs of choice for patients Beta-blockers are also the drugs of choice for patients with catecholaminergic Polymorphic VT (CPVT ). with catecholaminergic Polymorphic VT (CPVT ).

Mutation carriers of CPVT should also receive beta Mutation carriers of CPVT should also receive beta blockers even in the absence of documented VTblockers even in the absence of documented VT

SUDDEN CARDIAC DEATH

TAKE HOME POINTS

1.1. BB are strongly indicated in BB are strongly indicated in 2.2. HEART FAILURE, HEART FAILURE,

3.3. ACUTE MYOCARDIAL INFARCTION, ACUTE MYOCARDIAL INFARCTION,

4.4. POST MI CARDIAC PROTECTION, POST MI CARDIAC PROTECTION,

5.5. PREVENTION OF SCD,PREVENTION OF SCD, . .