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Vasodilating Beta Blockers The New Frontier. Abdul H Sankari, MD FACC FCCP. Disclosure. No major Holdings or Financial Assets in Pharmaceutical Co. Speakers Bureau for Abott Astra-Zeneca Forest Novartis Schering. OBJECTIVES. Identify the scope of Hypertensive Heart Disease.
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Vasodilating Beta BlockersThe New Frontier Abdul H Sankari, MD FACC FCCP
Disclosure • No major Holdings or Financial Assets in Pharmaceutical Co. • Speakers Bureau for • Abott • Astra-Zeneca • Forest • Novartis • Schering
OBJECTIVES • Identify the scope of Hypertensive Heart Disease. • Identify the shortcomings of traditional (non-vasodialating Beta Blockers). • Identify the advantages of the Vasodialating Beta Blockers.
Beta Blockers • The legacy
Beta Blockers • INDICATIONS • CAD • CHF • HTN • ATRIAL AND VENTRICULAR ARRHYTHEMIAS
Beta Receptors • B1 • Heart • Kidneys • Fat cells • B2 • Lungs • Skeletal Muscles • Liver/Pancreas
Vasodilating Beta blockers • Better side effect profile • Better Tolerability • Better efficacy
Side Effects of Traditional Beta Blockers • Fatigue • Sexual Dysfunction • Depression • Cold extremities • Decrease Exercise Tolerance • Metabolic side effects
But WHY? • Fatigue / Decrease Exercise Tolerance • Reduced CO & SV • Increased PVR (at least in the beginning of therapy)
Sexual Dysfunction • Decreased blood flow in the Corpora Cavernosa due to Vasoconstriction
Metabolic Changes • Increased insulin resistance • Lipid Metabolisem
Increased Insulin Resistance • Vasoconstriction causes decrease in micro-vascular surface area in skeletal muscle causing reduction in the insulin-mediated glucose entry and metabolism.
GEMINI: Relative to metoprolol, treatment with carvedilol stabilized hemoglobin A1c (HbA1c), a measure of glycemic control; improved insulin resistance; and slowed the development of microalbuminuria . Bakris GL. American Heart Association Scientific Sessions 2004. Nov 7-10, 2004; New Orleans, LA.
GEMINI: Progression to microalbuminuria Bakris GL. American Heart Association Scientific Sessions 2004. Nov 7-10, 2004; New Orleans, LA.
Lipid Metabolisem • Decreased Lipoprotein Lipase activity results in Increased LDL and Triglyceride levels, and decreased HDL.
Vasodilating Beta Blockers Improved Efficacy in CHF in Elderly and Obese Patients
COMET Trial Results Poole-Wilson P. European Heart Failure 2003 meeting; June 21-24, 2003; Strasbourg, France.
Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure (SENIORS) European Society of Cardiology Congress 2004
Main results of SENIORS trial Coats A. European Society of Cardiology Congress 2004; August 28-September 1, 2004; Munich, Germany.
SIGNIFICANT NOTE • around one third of heart-failure patients are actually receiving BB in clinical practice, because clinical trials have generally included younger patients (average age 61), whereas the average age of heart-failure patients in the real world was 76.
Elderly Patients • Decreased density of Beta receptors results in decreased efficacy in the elderly. • Vasodilating BB do not just work by blocking the Beta Receptors.
Obese patients • Traditional Beta Blockers results in 1.2 Kg/Yr weight gain due to reduced resting energy expenditure, and thermogenesis (by as much as 10% in some trials).