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.
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)
Increased Insulin Resistance
• Vasoconstriction causes decrease in micro-vascular surface area in skeletal muscle causing reduction in the insulin-mediated glucose entry and metabolism.
Bakris GL. American Heart Association Scientific Sessions 2004. Nov 7-10, 2004; New Orleans, LA.
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 .
End point Metoprolol p Carvedilol p
Mean HbA1c change with treatment, % (SD)
0.15 (0.04) <0.001 0.02 (0.04) 0.65
Insulin sensitivity (%)
-2.0 0.48 -9.1 0.004
GEMINI: Progression to microalbuminuria
Bakris GL. American Heart Association Scientific Sessions 2004. Nov 7-10, 2004; New Orleans, LA.
End point Metoprolol Carvedilol
Odds ratio (95% CI)
p
Progression to microalbuminuria (%)
10.3 6.4 0.60 0.04
Lipid Metabolisem
• Decreased Lipoprotein Lipase activity results in Increased LDL and Triglyceride levels, and decreased HDL.
COMET Trial Results
End point Carvedilol (n=1511) (%)
Metoprolol (n=1518) (%)
HR(95% CI)
p
All-cause mortality
33.9 39.5 0.83(0.74-0.93)
0.0017
All-cause mortality or all-cause hospitalization
73.9 76.4 0.93(0.86-1.10)
0.1222
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.
End point Nebivolol, n (%)
Placebo, n (%)
Hazard ratio (95% CI)
p
All-cause mortality/cardiovascular hospitalizations
332 (31.1) 375 (35.3)
0.86(0.73-0.99)
0.039
All-cause mortality
169 (15.8) 192 (18.1)
0.88(0.71-1.08)
0.214
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.