1.BETA BLOCKER USE IN CARDIOVASCULAR DISEASES Dr. dr. Hendro Darmawan, SpJP, FIHA PIT VI IDI Kota Bogor, 9 Nopember 2013

2. CVD (focused on) : 3. Classification of -blockers Table 6: Classification of -blockers1st GenerationNon-selectivePropranolol2nd Generation1-selectiveAtenolol Metoprolol Betaxolol Bisoprolol3rd GenerationAdditional properties, for example vasodilationCarvedilol Nebivolol 4. 1-selectivity of various blockers Bisoprolol 1:75AtenololBetaxolol1:351:35Metoprololincreasing 1-selectivity1:20no selectivity1.8:1 Propranololincreasing 2-selectivity300:1 ICI 118.551Ratio of constants of inhibitionWellstein A et al. J Cardiovasc Pharmacol 1986; 8 (Suppl. 11): 36-40 Wellstein A et al. Eur Heart J 1987; 8 (Suppl. M): 38 5. Beta 1 VS Beta 2 Selectivity 6. Elimination routes of various beta blockers from body 7. MECHANISM OF BETA BLOCKERS IN HEART FAILURE Upregulation of receptors and improved adrenergic signaling. 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 apoptosis. 8. Mechanism of -blocker benefits in ischemic heart disease Reduction in myocardial oxygen requirements via a decrease in heart rate, blood pressure and ventricular contractility. Slowing of the heart rate prolongs coronary diastolic filling period. Redistribution of coronary 9. Mechanism of -blocker benefits in ischemic heart disease Increases threshold to ventricular fibrillation. Reduction in infarct size and reduction in the risk of cardiac rupture. Reduction in the rate of reinfarction. Regression of the atheromatous 10. Summary of Trials of Beta-Blocker Therapy Phase of TreatmentTotal No. PatientsRR (95% CI)Acute treatment28,9700.87 (0.77-0.98)Secondary prevention24,2980.77 (0.70-0.84)Overall53,2680.81 (0.75-0.87)2 1 0.5 Relative risk (RR) of death Placebo Beta blocker better betterAntman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A textbook of Cardiovascular Medicine, 6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168. 11. MAINTATEUsefulness of beta-blocker therapy in patients with diabetes mellitus and CAD (BIP)1.000.90 0.85Mortality 42%With-blockers Without-blockers0.80 P = 0.00010.75 114.417 pts23Year45Jonas et al. Am J Cardiol 1996; 77: 1273 et seqq.Survival rate0.95 12. BP and -BLOCKERSCentral effects Baroreceptor reflexesCarotid sinus ?Stellate ganglionNE EReninSinus rate Stroke volume Cardiac outputTerminal neuroneAngio I Angio IISystemic vascular resistanceNE Initial rise then fall 13. BisoDIASEndgltig28Bisoprolol: Long-term treatment of hypertension140SBP(mm Hg)100DBP(mm Hg) HR(beats/min)600 n = 102121518212427303336 months10297102101102102102100102Giesecke HG et al. J Cardiovasc Pharmacol 1990; 16 (Suppl 5): 175180 14. This is how braunwalds textbook summarizes the use of betablockers in hypertension Beta blockers are specifically recommended forhypertensive patients with concomitant coronary disease, particularly after a myocardial infarction, congestive heart failure, or tachyarrhythmias. If a beta blocker is chosen, the agents that are more cardioselective offer the likelihood of fewer perturbations of lipid and carbohydrate metabolism and, because of fewer side effects (except for bradycardia), better adherence to therapy. Long-acting formulations are better for once-daily dosing. Page 945 braunwalds textbook of medicine 9th edition 15. From: Cardiovascular Protection Using Beta-Blockers: A Critical Review of the EvidenceJ Am Coll Cardiol. 2007;50(7):563-572. doi:10.1016/j.jacc.2007.04.060Figure Legend: Proposed Use of Beta-Blockers for HypertensionIn patients with uncomplicated hypertension, beta-blockers should not be used as first-line agents. However, in patients with uncontrolled hypertension on various other antihypertensive agents and in those with complicated hypertension, betablockers should be considered in the armamentarium of treatment. CHF = chronic heart failure; MI = myocardial infarction. College of Cardiology. Copyright The American All rights reserved. 16. Bisoprolol experience in Indian patients Mar 2012 17. Bisoprolol in hypertension Objectives:This study was aimed to evaluate the efficacy and tolerability of bisoprolol, in Indian patients diagnosed with stage I essential hypertension as first line drug. Primary and secondary outcomes measures:The primary outcome measure was percentage of patients achieving blood pressure (BP)