Adjunctive Therapy for Ischemic Wounds Using Cilostazol
Adjunctive Therapy for Ischemic Wounds Using Cilostazol
Twenty-five patients were identified as having lower-extremity wounds and ischemia, defined as an ankle-brachial index of 0.7 or less and an abnormal duplex scan combined with a clinical exam showing ischemia. All patients had corrective surgery for ischemia where indicated and, when the patients would allow it, had risk factors for nonhealing corrected as much as possible. All wounds had been in consistent, moist wound care for at least six weeks (6-52 weeks, average 12.5 weeks) without progress before beginning cilostazol. After beginning cilostazol (while maintaining standard wound care), 60 percent of the patients progressed to healing in 60 days with findings of progressive wound healing beginning as early as 10 days after instituting cilostazol. Of the remaining (40%), half (20%) did not heal until other interventions were performed and half (20%) deteriorated. Cilostazol appears to offer adjunctive wound healing benefits in ischemic wounds of the lower extremities.
Cilostazol (Pletal, Otsuka Pharmaceutical Co., Rockville, Maryland) has been available in the United States as an oral medication for the treatment of intermittent vascular claudication since 1999. Claudication is the current Food and Drug Administration indication for use of the drug, and improvement in claudication on cilostazol directly correlates with an increase in blood flow in the affected limb.
Cilostazol belongs to a group of drugs that are cyclic adenosine monophosphate phosphodiesterase inhibitors. As such, the drug shows activities leading to inhibition of platelet aggregation, vasodilatation, improvement of dyslipidemia, inhibition of smooth muscle proliferation, and increase in blood flow in limbs with stenotic or occluded arteries. At this time, the authors are reporting an apparent beneficial effect on wound healing in ischemic limbs using cilostazol.
Symptoms of chronic arterial occlusion, leg claudication, and pain frequently precede ischemic ulceration in the lower extremities. In 42 percent of lower-extremity ulcers in nondiabetic patients and 67 percent of lower-extremity ulcers in diabetic patients, compromise of arterial blood flow makes a significant contribution to the healing problems of these wounds.
In the diabetic patient, concomitant neuropathy may prevent the patient from adequately appreciating their ischemic pain. Although injuries to the legs and feet of patients with arterial disease may not occur because of ischemia, they often fail to heal because of arterial disease. Thus, a diabetic patient who usually acquires a foot ulcer from repeat trauma, unrecognized in the presence of neuropathy, may not heal primarily because of underlying arterial disease. This has also been seen in the authors' experience in neuropathic patients with other injuries, including venous ulcer patients and patients with blunt trauma.
Therapeutic interventions for ischemic lower-extremity ulcers usually consist of topical wound care and interventions that improve arterial supply. If arterial circulation is severely compromised, revascularization of the ischemic area by angioplasty, bypass surgery, or both is usually done. Control and correction of nutrition and metabolic problems are also addressed.
Topical wound care in the authors' area consists of debridement and maintenance debridement, moist wound care with nontoxic agents, occasional use of modalities of electrical stimulation, and ultrasound with control of bacterial involvement in the wound. Reconstructive techniques, such as skin graft and myocutaneous flaps, may be necessary to expedite closure of the ulcers after bacterial colonization has been controlled and healing has begun.
Multiple clinical trials have been performed using cilostazol for intermittent claudication with a great deal of success. In a placebo-controlled, randomized trial, Dawson, et al., demonstrated on treadmill testing a 35-percent increase in initial claudication distance and a 41-percent increase in maximal walking distance in patients treated with cilostazol. Other indices of improvement with cilostazol in claudicants include improved ankle-brachial index. Investigators have also demonstrated an increase in blood flow and cross-sectional area in the dorsalis pedis artery with cilostazol in an open trial.
There have been reported experiences with cilostazol in the treatment of skin wounds. Kondo treated 24 patients with ulcers from collagen diseases in an open-label study and found a significant decrease in the size of the ulcer. Arakawa and Arada evaluated the efficacy of cilostazol 100mg twice daily in patients with poorly healing skin ulcers and other dermatologic problems associated with vascular disorders. Twenty-one subjects were treated for a minimum of six weeks. Improvement was demonstrated by a decrease in pain, numbness, rest pain, and erythema. Subjects with diabetes showed the greatest improvement. Overall, 48 percent showed marked improvement of symptoms and 24 percent showed some improvement. Arakawa and Arada concluded that cilostazol could be useful in the treatment of skin ulcers associated with vascular disorders.
Early on in the course of the authors' use of cilostazol in ischemic disease of the lower extremities, the authors noted an obvious trend towards healing of wounds in the legs and feet of most of these patients. All of these patients were given cilostazol based on the indication of claudication-type ischemia of the legs confirmed by physical exam and duplex Doppler exam.
Twenty-five patients were identified as having lower-extremity wounds and ischemia, defined as an ankle-brachial index of 0.7 or less and an abnormal duplex scan combined with a clinical exam showing ischemia. All patients had corrective surgery for ischemia where indicated and, when the patients would allow it, had risk factors for nonhealing corrected as much as possible. All wounds had been in consistent, moist wound care for at least six weeks (6-52 weeks, average 12.5 weeks) without progress before beginning cilostazol. After beginning cilostazol (while maintaining standard wound care), 60 percent of the patients progressed to healing in 60 days with findings of progressive wound healing beginning as early as 10 days after instituting cilostazol. Of the remaining (40%), half (20%) did not heal until other interventions were performed and half (20%) deteriorated. Cilostazol appears to offer adjunctive wound healing benefits in ischemic wounds of the lower extremities.
Cilostazol (Pletal, Otsuka Pharmaceutical Co., Rockville, Maryland) has been available in the United States as an oral medication for the treatment of intermittent vascular claudication since 1999. Claudication is the current Food and Drug Administration indication for use of the drug, and improvement in claudication on cilostazol directly correlates with an increase in blood flow in the affected limb.
Cilostazol belongs to a group of drugs that are cyclic adenosine monophosphate phosphodiesterase inhibitors. As such, the drug shows activities leading to inhibition of platelet aggregation, vasodilatation, improvement of dyslipidemia, inhibition of smooth muscle proliferation, and increase in blood flow in limbs with stenotic or occluded arteries. At this time, the authors are reporting an apparent beneficial effect on wound healing in ischemic limbs using cilostazol.
Symptoms of chronic arterial occlusion, leg claudication, and pain frequently precede ischemic ulceration in the lower extremities. In 42 percent of lower-extremity ulcers in nondiabetic patients and 67 percent of lower-extremity ulcers in diabetic patients, compromise of arterial blood flow makes a significant contribution to the healing problems of these wounds.
In the diabetic patient, concomitant neuropathy may prevent the patient from adequately appreciating their ischemic pain. Although injuries to the legs and feet of patients with arterial disease may not occur because of ischemia, they often fail to heal because of arterial disease. Thus, a diabetic patient who usually acquires a foot ulcer from repeat trauma, unrecognized in the presence of neuropathy, may not heal primarily because of underlying arterial disease. This has also been seen in the authors' experience in neuropathic patients with other injuries, including venous ulcer patients and patients with blunt trauma.
Therapeutic interventions for ischemic lower-extremity ulcers usually consist of topical wound care and interventions that improve arterial supply. If arterial circulation is severely compromised, revascularization of the ischemic area by angioplasty, bypass surgery, or both is usually done. Control and correction of nutrition and metabolic problems are also addressed.
Topical wound care in the authors' area consists of debridement and maintenance debridement, moist wound care with nontoxic agents, occasional use of modalities of electrical stimulation, and ultrasound with control of bacterial involvement in the wound. Reconstructive techniques, such as skin graft and myocutaneous flaps, may be necessary to expedite closure of the ulcers after bacterial colonization has been controlled and healing has begun.
Multiple clinical trials have been performed using cilostazol for intermittent claudication with a great deal of success. In a placebo-controlled, randomized trial, Dawson, et al., demonstrated on treadmill testing a 35-percent increase in initial claudication distance and a 41-percent increase in maximal walking distance in patients treated with cilostazol. Other indices of improvement with cilostazol in claudicants include improved ankle-brachial index. Investigators have also demonstrated an increase in blood flow and cross-sectional area in the dorsalis pedis artery with cilostazol in an open trial.
There have been reported experiences with cilostazol in the treatment of skin wounds. Kondo treated 24 patients with ulcers from collagen diseases in an open-label study and found a significant decrease in the size of the ulcer. Arakawa and Arada evaluated the efficacy of cilostazol 100mg twice daily in patients with poorly healing skin ulcers and other dermatologic problems associated with vascular disorders. Twenty-one subjects were treated for a minimum of six weeks. Improvement was demonstrated by a decrease in pain, numbness, rest pain, and erythema. Subjects with diabetes showed the greatest improvement. Overall, 48 percent showed marked improvement of symptoms and 24 percent showed some improvement. Arakawa and Arada concluded that cilostazol could be useful in the treatment of skin ulcers associated with vascular disorders.
Early on in the course of the authors' use of cilostazol in ischemic disease of the lower extremities, the authors noted an obvious trend towards healing of wounds in the legs and feet of most of these patients. All of these patients were given cilostazol based on the indication of claudication-type ischemia of the legs confirmed by physical exam and duplex Doppler exam.
