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Home > Vascular Annual Meeting > odonnell_randomized_controlled

Randomized Controlled Trial Assessing the Effects of Cilostazol on Exercise-Induced Ischaemia-Reperfusion in Patients with Peripheral Arterial Disease

Mark E. O'Donnell¹, Stephen A. Badger¹, Mohammed A. Sharif¹, Ragai R. Makar¹, Jane McEneny², Ian S. Young², Louis L. Lau¹, Bernard Lee¹, Raymond J. Hannon¹, Chee V. Soong.^1
1Belfast City Hospital, Belfast, United Kingdom;²Department of Medicine, Queens University Belfast, Belfast, United Kingdom.

OBJECTIVES: The phosphodiesterase-3 inhibitor cilostazol improves walking distance in peripheral arterial disease (PAD) patients through an increase in cyclic AMP levels. The study objectives were to assess the effects of cilostazol on exercise-induced ischemia reperfusion in such patients.

METHODS: PAD patients were prospectively recruited to a randomized double-blinded, placebo-controlled trial. Baseline clinical data were recorded following medical optimization. Initial (IWD) and absolute (AWD) walking distances were measured on a validated treadmill protocol. Inflammatory response was assessed pre and 30-minutes post-exercise by serum lipid hydroperoxide, interleukins 6 and 10, 11-dehydro thromboxane B2 (TXB2), cell-adhesion-molecules (I-CAM & V-CAM), P-selectin, α-tocopherol and highly-selective C-reactive protein (hsCRP) measurements, and by plasma ascorbate and urinary p75TNF receptor analyses. All tests were at baseline, 6 weeks and 24 weeks.

RESULTS: 106 PAD patients (72 males) were recruited from 2004 to 2006 (overall median age: 66.5, range 37-86). 26 patients were diabetic. Treatment limbs were demographically and medically matched. Patients who received cilostazol, compared to placebo, demonstrated a mean improvement from baseline in AWD (77.2% vs. 26.6% and 161.7% vs. 79.0% at 6 and 24 weeks, p<0.05, MWU-test). There was a reduction from baseline lipid hydroperoxide levels in the cilostazol group compared to an increase in the placebo group pre and post exercise (6-weeks: pre: - 11.8% vs. + 5.8% and post: - 12.3% vs. + 13.9%) (24-weeks: pre: - 15.5% vs. + 12.0% and post: - 9.2% vs. + 1.9%) (p<0.03, MWU). Cilostazol significantly reduced TXB2, I-CAM, V-CAM, and P-selectin levels at 24 weeks compared to baseline levels (p<0.05, WSR-test). Mean percentage change from baseline for &alpha;-tocopherol levels were also reduced in the active treatment group pre and post exercise at 24 weeks (pre: - 8.4% vs. + 3.2% and post: - 9.7% vs. + 4.7%) (p<0.01, MWU). Although there were trends for improvements in ascorbate and hsCRP levels, these were not significant. There was no difference between groups for interleukins and p75TNF levels.

CONCLUSIONS: Cilostazol attenuates an exercise-induced ischaemia-reperfusion effect in PAD patients in combination with significant improvements in claudication distance.

AUTHOR DISCLOSURES: M.E. O'Donnell, Insulin Dependant Diabetes Trust.; Royal College of Surgeons Edinburgh, Scotland; Belfast City Hospital Vascular Research Fund; Otsuka Pharmaceuticals Provided the Placebo for the Study.; Attendance at the Vascular Society Meeting 2007 in England; S.A. Badger, None; M.A. Sharif, None; R.R. Makar, None; J. McEneny, None; I.S. Young, None; L.L. Lau, None; B. Lee, None; R.J. Hannon, None; C.V. Soong, None.