title: Effects of cilostazol on arterial wound healing: a retrospective analysis.
abstract: BACKGROUND
  The vasodilator cilostazol (Pletal(®)), a phosphodiesterase-3 inhibitor, is approved in the United States for treatment of intermittent claudication. This study was aimed at evaluating its efficacy as an adjunct in the management of arterial ulceration.
  
  
  METHODS
  The clinical records of patients treated with cilostazol from 2000 to 2010 at one institution were obtained. Of the 561 patients treated with cilostazol, we identified 82 (101 limbs) who started on therapy only after wounds were present and whose records were sufficient to assess healing. Only if all wounds in a limb completely healed without intervening arterial reconstruction, amputation, primary closure, or skin grafting, the limb was deemed healed with the assistance of cilostazol. With bilateral involvement, both limbs had to heal for the patient to be judged healed. Subjects who were lost to follow-up, died, or underwent surgical interventions other than debridement were deemed failures. Age, weight, height, body mass index (BMI), creatinine, diabetes, insulin therapy, hemodialysis, smoking history, congestive heart failure, cilostazol dose, and length of therapy were compared, as well as, the number of wounds, size of largest wound, chronicity, ankle-brachial index, the presence of exposed bone/tendon/joint, or the presence of gangrene.
  
  
  RESULTS
  Overall 30 of 82 patients (36.6%) and 41 of 101 (40.6%) limbs were deemed healed without surgical intervention or revascularization (open or endovascular). When 9 limbs that healed after skin grafts (n = 2) or foot-sparing amputations (n = 7) but without revascularization were considered, the overall rate of lower extremity limb salvage was 50.5%. Demographic characteristics were similar in the 2 groups except healed patients tended to be taller and weigh more but had similar BMI. The incidence of diabetes was higher in nonhealed limbs (73.3% vs. 50.0%, P = 0.0587). Gangrene was less common in healed patients (22.6% vs. 49.1%, P = 0.059) and healed limbs (22.0% vs. 48.3%, P = 0.027). Most subjects received 200 mg of cilostazol daily (healed:177 ± 53 mg vs. nonhealed: 172 ± 47 mg). Mean length of therapy in healed patients was 278 ± 302 days compared with 108 ± 129 days in nonhealed subjects before discontinuation of drug therapy or surgery, death, or loss to follow-up intervened.
  
  
  CONCLUSIONS
  The observed limb healing rate with cilostazol compares favorably to the ~20% rate observed in subjects treated with placebo in multicenter trials of another vasodilator, iloprost. Although gangrene and diabetes correlate with lower prospects for healing, our data suggest that cilostazol helps promote healing of wounds when arterial insufficiency is present.
authors.affiliation: Long Beach Veterans Administration Health Care System, Long Beach, CA; Department of Surgery, University of California Irvine, Irvine, CA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Resnick
authors.affiliation: Long Beach Veterans Administration Health Care System, Long Beach, CA; Department of Surgery, University of California Irvine, Irvine, CA. Electronic address: ian.gordon@va.gov.
authors.forename: Ian L
authors.initials: IL
authors.lastname: Gordon
mesh_terms: D000368:Aged; D000077407:Cilostazol; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007871:Leg Ulcer / Q000175:diagnosis / Q000188:drug therapy*; D023821:Limb Salvage; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000188:drug therapy*; D058987:Phosphodiesterase 3 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D034941:Upper Extremity / Q000098:blood supply*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D000077407:Cilostazol