Q. Please review some new cardiac drugs that can be used in clinical practice today.
A. Dr. Bonnie K. Lefbom at the 2005 American College of Veterinary Internal Medicine Forum in Baltimore gave a lecture on sildenafil
and novel cardiovascular therapies. Some relevant points in this lecture and current information about ramipril are provided
New treatment modalities often arise in cardiac therapy. Sildenafil was initially disregarded in its development as a useful
tool for coronary heart disease. However, the discovery that sildenafil was effective to combat impotence transformed into
a breakthrough therapy for individuals suffering from debilitating pulmonary hypertension. Pimobendan, a drug initially discounted
because former drugs in its class were shown to predispose to life-threatening arrhythmias, has combined vasodilator and positive
inotropic effects via phosphodiesterase inhibition. Pimobendan is emerging as therapy for dogs with late-stage contractile
failure. Nutraceutical therapy always has been under scrutiny. B-vitamin complex therapy, however, has been shown to decrease
circulating levels of homocysteine. High homocysteine levels increase risk for thrombotic events.
Sildenafil was introduced in 1998 under the trademark of Viagra and received intense media coverage of any newly approved
drug. The mechanism of action is via inhibition of cGMP degradation via specific phosphodiesterase-5 (PDE-5) inhibition. PDE-5
is plentiful in vascular, tracheal and visceral smooth muscle. Nitric oxide (NO) and cGMP act synergistically to reduce calcium
release from intracellular stores and serve to improve smooth-muscle relaxation allowing arterial dilation in several clinical
examples. Clinically, there are few alternatives to treat individuals with debilitating pulmonary hypertension (PHT). Sildenafil
recently has been demonstrated in human cardiology to decrease the severity of PHT in both primary (unknown cause) and secondary
disease, including left-sided congestive heart failure (CHF). In fact, a single dose of sildenafil has been shown to be a
selective pulmonary vasodilator and may even be superior to inhaled NO based on its increase in cardiac output with no increase
in capillary wedge pressure. Veterinary cardiologists now are adding this drug as an adjunct to traditional pulmonary hypertension
therapy. Initial clinical results using a dose of 1-3 mg/kg two to four times daily have been promising.
Pimobendan is a benzimidazole derivative that exerts its positive inotropic and vasodilatory actions through both calcium
sensitization and phosphodiesterase inhibition. Initial reports in human medicine from Europe and Japan suggested beneficial
effects of pimobendan on the neurohumoral factors when added to standard therapy for individuals with moderate (NYHA functional
class II-III) heart failure. Subsequent larger-scale trials in human patients on pimobendan demonstrated decreases in morbidity
(not mortality) and increases in physical activity of human patients with mild to moderate CHF. Initial small-scale trials
with English Cocker Spaniels (ECS) and Doberman Pinschers (DP) demonstrated significant improvement in heart failure class
for both the ECS and DP groups when pimobendan was added to standard triple therapy for heart failure (furosemide, digoxin
and enalapril). Also, a marked improvement in survival times was demonstrated in the DP group on pimobendan compared to DP
dogs on standard triple therapy and placebo. No significant change in survival times for ECS dogs was noted. A second small-scale
study confirmed the positive effects on both quality and duration of life in DP dogs when given pimobendan as adjunct therapy
for congestive heart failure. The two larger trials attempted to compare the effects of ACE inhibition with pimobendan. The
clinical status of dogs on pimobendan was improved compared with ACE inhibitors. However, no statistical differences were
found in hospitalization rates or maximum diuretic doses required to maintain dogs out of heart failure. Pimobendan was shown
to have fewer adverse outcome reports when compared to ramipril and does appear to be safe in congestive heart failure in
dogs. The currently accepted dose is 0.2 to 0.3 mg/kg twice daily.
As with all newly released pharmaceuticals, caution with the use of pimobendan is warranted until larger-scale trials are
completely analyzed, true benefits are outlined and potential side effects disclosed.