Pharmacological Treatment of Peripheral Vascular Disease
Warren W. McMurry, MD, FACS

Peripheral Vascular Disease (PVD) is very prevalent in the U.S. Incidence increases in association with risk factors such as smoking, hyperlipidemia, positive family history, diabetes, male gender, and increasing age. One of the most debilitating symptoms of PVD in terms of interference with lifestyle and/or ability to work is claudication (fatigue or discomfort in the musculature of the lower extremities with exercise or increasing workload). It is estimated that over four million people in the U.S. have claudication symptoms. Many of these patients can benefit from carefully performed open vascular or endovascular surgical procedures. However, some patients are not candidates for open surgical procedures due to underlying co-morbid factors. This is occasionally true for endovascular procedures as well although there is not doubt that the advent of endovascular techniques has opened interventional doors not previously available to frail individuals. Other patients are not candidates for surgical procedures due to the nature and/or extent of their PVD (i.e., problem can't be corrected surgically). These patients are left with medical management as their only recourse.

Medical management of PVD-related claudication symptoms includes smoking cessation, exercise, weight loss, control of hypertension, control of hyperlipidemia, and pharamacological therapy. A platelet inhibitor such as aspirin is generally felt to be beneficial to help slow progression of disease but tends to have little or no effect on claudication symptoms. Otherwise, pharmacological choices for beneficial management of claudication are limited. One of these medications, pentoxifylline (Trental®), has been available for several years. A new arrival on the scene is cilostrazol (Pletal®).

Trental® was approved for use in the U.S. for claudication sometime in the mid-1980's. Within the past couple of years, the patent has expired and generic preparations are now available. This drug is primarily a hemorrheologic medication. Its benefits in claudication are thought to be due to improved blood flow characteristic in capillary beds (microcirculation). This is brought about by multiple effects including increased cell membrane deformability of both red blood cells and white blood cells and decreased aggregation of RBCs, WBCs, and platelets, among others. The usual dose of this medication is 400 mg TID given with food so as to decrease gastrointestinal upset. GI irritability is one of the main side effects and is seen in up to 10% of patients. It can sometimes be corrected by dose reduction, but some patients simply cannot tolerate the medication. Beneficial effects on claudication symptoms may not be seen for 6-8 weeks so the medications should generally be tried for up to 3 months before giving up on it Typical cost of this medication at the TID dosing schedule is around $65.00 per month. Generic formulations of this medication are available for around $40.00 for a month's supply.

In the past 4-6 months, Pletal® has received FDA approval for use in claudication and has become commercially available in the U.S. Its primary actions are those of platelet aggregation suppression and arterial vasodilatation. It is thought to be 10-30 times more potent than aspirin in platelet aggregation inhibition. The drug also has been shown to enhance endothelial derived prostacyclin activity. Additional beneficial effects which have been noted in some studies, but which bear further investigation, include decreases in triglyceride levels and increase in HDL cholesterol levels. The usual dose for this medication is 100 mg BID taken on an empty stomach. Some patients have noted benefit in claudication symptoms in as little as 2-4 weeks. However, the medicine should generally be tried for 8-12 weeks before giving up on it. The most common side effect is headache, but this usually can be treated with nonnarcotic analgesics and tends to be self-limited. The next two most common side effects are gastrointestinal disturbance (diarrhea usually) and dizziness. The drug is contraindicated in moderate to severe congestive heart failure, and doses should be reduced in patients taking medications metabolized by the cytochrome oxidase pathway in the liver such as erythromycin, diltiazem, and omeprazole, to name a few. The approximate cost of this medication for the 100 mg BID dosing is around $92.00 per month. As Pletal® is a new medication, it may not be covered under some managed care plans.

Both of the above drugs have been shown to be beneficial in medical management of claudication. Results of head-to-head comparisons between the two are not routinely available as yet. What is more, since the mechanisms of action are different, there will be the questions of whether or not the medications can, or should, be used concurrently. Health care providers should not substitute pharmacological management when patients are appropriate candidates for surgical management as the long-term physical and financial benefits favor open vascular or endovascular surgical intervention.