Personalized Cardiology - Applications of Biotechnology in Cardiovascular Therapeutics - page 323

b-blocker titration and thus may require more frequent follow-up during titration
(Terra et al. 2005 ).
Bucindolol
Bucindolol's unique pharmacodynamics in advanced heart failure patients produce
either a hyper-response (a beta1 receptor polymorphism) or avoid an adverse effect
(an alpha2c receptor polymorphism). These dual gene loci create a set of diplotypes
characterizing the population. By identifying important genetic factors underlying
heart failure and the response to bucindolol, Arca Discovery Inc has identified those
patients who will benefit most from bucindolol treatment. A polymorphism within
a conserved beta(1)-adrenergic receptor motif alters cardiac function and b-blocker
response in human heart failure. A study concluded that beta(1)AR-389 variation
alters signaling in multiple models and affects the b-blocker therapeutic response
in heart failure and, thus, might be used to individualize treatment of the syndrome
(Liggett et al. 2006 ).
When prescribed genetically, bucindolol will be the state of the art in heart fail-
ure treatment for a majority of the of the US heart failure population. Bucindolol's
unique pharmacology gives it other advantages as well, such as superior myocardial
infarction clinical endpoints and tolerability.
BiDil
Enalapril therapy is associated with a significant reduction in the risk of hospitaliza-
tion for heart failure among white patients with left ventricular dysfunction, but not
among similar black patients. This finding underscores the need for additional
research on the efficacy of therapies for heart failure in black patients. This analysis,
combined with other recent data from clinical trials, suggests that the overall popu-
lation of black patients with heart failure may be underserved by current therapeutic
recommendations. The fact that large-scale trials of therapy for heart failure have
been performed in preponderantly white populations has limited the ability of the
medical community to assess the efficacy of current therapies in black patients.
The relatively high level of heart failure in the black population has been attrib-
uted, in part, to a lack of nitric oxide (NO). BiDil (NitroMed), made of isosorbide
dinitrate and hydralazine, is thought to reduce mortality in this population by
restoring depleted NO levels, and by protecting NO that is formed naturally in
vascular endothelial cells. A randomized trial has examined whether a fixed dose
of Bidil provides additional benefit in blacks with advanced heart failure, a sub-
group previously noted to have a favorable response to this therapy (Taylor et al.
2004 ). Hydralazine is an antioxidant and vasodilator, which means that it protects
NO formed by isosorbide dinitrate and dilates blood vessels. Neither drug is indicated