Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 51

Iloprost is indicated for the treatment of patients with PAH (WHO Group 1) with
NHYA Class III or IV symptoms. It significantly increases patient improvement
after 12 weeks of treatment compared to baseline on a composite endpoint of
improved exercise capacity 30 min after dosing, improvement of at least one
NHYA class and no clinical deterioration. It significantly improves 6 min walk
distance at week 12 with a 10% or greater increase in individual walk distance.
Although inhaled iloprost has been approved for the treatment of adults with PAH,
a study showed that it caused sustained functional improvement in some children
with PAH, although it occasionally induced bronchoconstriction (Ivy et al. 2008 ).
Most patients tolerated the transition from intravenous to inhaled prostanoid
therapy.
Endothelin Receptor Antagonist Treatment of PAH
Bosentan (Actelion's Tracleer ® ), the first oral dual endothelin receptor antagonist,
is approved for the treatment of PAH and made available by subsidiaries in the
USA, the EU, Japan, Australia, Canada, Switzerland, and other markets worldwide.
Tracleer ® has a label extension in the USA for the treatment of patients with mildly
symptomatic WHO Functional Class II PAH. Results of a randomized study dem-
onstrate that the addition of inhaled iloprost in patients with PAH with reduced
exercise capacity on bosentan monotherapy is safe and efficacious (McLaughlin
et al. 2006 ).
Anticoagulation in Cardiovascular Disease
Anticoagulation is used for the prophylaxis and treatment of vascular thrombosis.
Many cardiovascular disorders are characterized by thromboembolism. Deep venous
thrombosis may occur from prolonged immobilization or inactivity. Heparin, one of
the most potent anticoagulants widely used for the treatment and prevention of deep
vein thrombosis and pulmonary embolism, is currently available to patients only by
parental administration.
Oral Heparin
Currently, the most common indication for heparin therapy is the prevention of
blood clot formation following major surgical procedures lasting longer than
30 min, such as angioplasty or heart surgery. Emisphere is developing an oral for-
mulation of heparin. Unfractionated heparin and warfarin have been the most commonly
prescribed anticoagulant agents to prevent thrombus formation. Generally, physicians
prefer heparin over warfarin because heparin has a rapid onset of anticoagulant
activity, a short physiological half-life and significantly fewer incidences of drug-
drug interactions. These pharmacological properties facilitate dose adjustment and
contribute to heparin's relatively large margin of safety.