Journal Reading Effects of Cilostazol on Arterial Wound Healing: A Retrospective Analysis

Journal ReadingEffects of Cilostazol on Arterial WoundHealing: A Retrospective AnalysisTaufan H Dewangga,dr131621130506Introduction1980s in Japan a drug for the treatment of critical limb ischemiaA phosphodiesterase-3 inhibitor to increased intracellular levels of cAMP, by promoting activation of protein kinase vascular smooth muscle relaxation and vasodilation of the peripheral arterial circulation.Induce dilation of the pedal arteries and increase limb blood flow in humans with peripheral arterial disease (PAD)Increases in ankle pressures and more rapid recovery of ankle pressures after exerciseThermographic studies show that cilostazol therapy increases lower extremity skin temperature in subjects with PADOther effects include : inhibition of platelet aggregation, reduction of risk for thrombotic stroke, andinhibition of myointimal hyperplasia after coronary artery stenting

IntroductionCilostazol was approved by the United States Food and Drug Administration (FDA) in 1999 for treating intermittent claudication secondary to PAD,And in managing critical limb ischemia including ulcers and wounds induced by arterial insufficiencyIntroductionOver the last decade, cilostazol treated >500 subjects with PAD, of which 20% had tissue loss or ulcers.Dramatic improvements and healing in wounds of both the upper and lower extremities To figure out efficacy of cilostazol in promoting arterial wound healing, we have retrospectively analyzed the clinical records of patients with wounds who received cilostazolIntroduction

(A) A 60 y.o Caucasian male in August 2001 with a 4-month history of a nonhealing ulcer on the medial aspect of the right ankle.(B) Three years earlier, he undergone suprageniculate femoropopliteal bypass with a polytetrafluorethylene conduit that was thrombosed. The ABI was 0.61.

Physical examination venous insufficiencyStarted on compression therapy with multiple-layer dry bandages and topical silvadene. The wound showed no change in size after 2 months, and he was scheduled for repeat lower extremity bypass. He was started on cilostazol. Marked wound healing was evident at follow-up a week later,Surgery was subsequently deferred as complete wound healing was achieved within 4 weeks with continued compressionA list of all patients for whom cilostazol was dispensed between August 2000 and September 2010 was provided by the pharmacy service, and their charts were reviewedIn each case, we confirmed that the medication had been dispensed and that with prolonged therapy refills had been provided based on pharmacy records. Subjects were started on 50-mg cilostazol twice daily for 2 to 4 weeks Increased to 100 mg twice daily unless significant adverse effects were observed (e.g., diarrhea and tachycardia).

MATERIALS AND METHODSInclusion:Only patients with full-thickness wounds or ulcers Subjects with failed revascularization before cilostazol initiation Nonhealing incisions after previous surgery or amputation (wound dehiscence) Nonhealing wounds after thrombosis of previously patent arterial reconstructionsExclusion:If refills should have been provided but were not documented, or if we could not confirm that cilostazol had been taken by a patientSubjects who had undergone successful revascularization within 6 months of starting cilostazol or immediately after starting cilostazolMATERIALS AND METHODSHeal :Operative surgical debridement without amputation was not a marker of therapeutic failureWounds completely healed without arterial reconstruction, primary closure, or amputation, In patients with bilateral limb involvement, both limbs had to experience complete healing Not HealPatients who were lost to follow-up or died without evidence for healing,Who underwent revascularization, primary closure, or skin grafting, Who underwent amputation of the wounded portion of a limbMATERIALS AND METHODS

561 subjects had prescriptions for cilostazole8 never took medication435 didnt have significant extremity wounds29 had extremity wound develop after commencing cilostazole not included

89 started cilostazol therapy7 CR not sufficiently CR sufficient

MATERIALS AND METHODS110 limbs cilostazole therapy6 upper ext104 lower ext9 not adequate to determine a response101 efficacyMATERIALS AND METHODSDemographic parameter analized :- Age- Weight- Height- Body mass index- Diabetes- Tobacco use- Renal failure requiring hemodialysis- Congestive heart failure- Albumin- Creatinin- Duration of theraphyMATERIALS AND METHODSLimb and wound characters analyzed :ankle-brachial index (ABI), largest wound size per extremity, number of wounds per extremity, Chronicity of the wound before starting cilostazol, Presence of gangrene, and presence of exposed bone, tendon, or jointIn the analysis by patient, if both limbs were wounded, the lower ABI was used.MATERIALS AND METHODS101 limbs 41 (40,6%) healed60 did not healupper ext (6)2 wounded (33%) healed4 did not healLower ext (95)39 (41.1%) healed56 (58.9%) did not heal82 patients amenable to analysis :30 (36.6%) complete healing52 non healedRESULTS

101 limbs with ischemic tissue loss or ulceration41 limbs (40.6%) complete healing30 (36.6%) from82 patients complete healing of all extremity woundsHealing was less likely in subjects with gangrene, diabetes and active smokers at the time therapy was initiatedSubjects who were treated with cilostazol tended to have long courses of therapy before complete healing (mean: 9.7 months).

DISCUSSIONWeakness :Review of small number of patients and limbs and is underpowered to detect significant differences between the healed and nonhealed limbsIdeally should have a control group of patients, who are managed without cilostazol, with comparable ischemiawe did not directly confirm compliance with the prescribed cilostazol regimen by counting tablets or using diaries

DISCUSSIONNonetheless despite these methodological problems, in several cases, we saw dramatic healing soon after starting cilostazolDISCUSSION

The Healing of Ischemic Foot Ulcers with Cilostazol Trial (HEAL-IT) : multicenter, prospective, placebo-controlled, double-blind, randomized trial to evaluate cilostazols effect on marginally ischemic ulcersDesigned to select subjects with borderline arterial perfusionThe goal to assess the efficacy of cilostazol in promoting healing in wounds where perfusion was likely to be borderline

DISCUSSIONTranscutaneous PO2 measurements at the foot or toe pressures had to be between 20 and 40 mm HgPressures >40 mmHg, healing rates are >90% Pressures