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Safety and efficacy of cilostazol in the management of intermittent claudication.

Chi YW, Lavie CJ, Milani RV, White CJ - Vasc Health Risk Manag (2008)

Bottom Line: Besides surgical and endovascular interventions to improve limb-specific outcomes, pharmacotherapy is an effective tool in the treatment of IC.Cilostazol, a Federal Drug Administration-approved medication for the treatment of IC, has demonstrated consistent efficacy in improving exercise capacity and overall health-related QoL.This manuscript will review the pharmacokinetics, safety, and efficacy of cilostazol in the treatment of patients with IC as well as compare this agent with other proven non-invasive therapies for PAD.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Section of Vascular Medicine, Ochsner Health System, 2005 Veterans Blvd., Metairie, LA 70002, USA. ychi@ochsner.org

ABSTRACT
Peripheral arterial disease (PAD) is a major health problem affecting millions of patients worldwide. Many will suffer from intermittent claudication (IC), which leads to marked impairment of quality of life (QoL). Besides surgical and endovascular interventions to improve limb-specific outcomes, pharmacotherapy is an effective tool in the treatment of IC. Cilostazol, a Federal Drug Administration-approved medication for the treatment of IC, has demonstrated consistent efficacy in improving exercise capacity and overall health-related QoL. This manuscript will review the pharmacokinetics, safety, and efficacy of cilostazol in the treatment of patients with IC as well as compare this agent with other proven non-invasive therapies for PAD.

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Related in: MedlinePlus

Mean percent change in maximal walking distance (MWD) among intermittent claudication patients receiving cilostazol 100 mg 2×/day (n = 140), cilostazol 50 mg 2×/day (n = 139), or placebo (n = 140) for 24 weeks. Reprinted from Beebe, HG, Dawson DL, Cutler BS, et al 1999. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med, 159:2041–50. Copyright © 1999 with permission from American Medical Association.
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f3-vhrm-4-1197: Mean percent change in maximal walking distance (MWD) among intermittent claudication patients receiving cilostazol 100 mg 2×/day (n = 140), cilostazol 50 mg 2×/day (n = 139), or placebo (n = 140) for 24 weeks. Reprinted from Beebe, HG, Dawson DL, Cutler BS, et al 1999. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med, 159:2041–50. Copyright © 1999 with permission from American Medical Association.

Mentions: Once the goals of risk factor modification for patients with PAD have been met, the focus of PAD management shifts from general cardio-protection to treatment strategies specific for the clinical manifestations of PAD such as IC. There are consistent data supporting the efficacy of cilostazol for IC. In one the of most important studies included in the agent’s New Drug Application, 698 patients with moderate to severe IC were randomized to a standard dose of cilostazol 100 mg 2×/day, a standard dose of pentoxifylline (400 mg 3×/day), or placebo (3×/day) for a period of 24 weeks. By the end of the study, patients included in the cilostazol group had shown a 54% improvement in maximal walking distance from the baseline compared with increases of 30% in the pentoxifylline group (p < 0.05) and 34% in the placebo group (p < 0.05) (Figure 2) (Dawson et al 2000). Earlier trials have demonstrated a dose-response relationship with cilostazol. In one study (Beebe et al 1999), IC patients who received cilostazol 100 mg 2×/day for 24 weeks increased their maximal walking distance by 51% over the baseline, whereas those who received a 50 mg 2×/day dose showed an increase of only 38% compared to baseline values (p < 0.001 for both doses versus placebo) (Figure 3). In a second trial, the net improvement in maximal walking distance over placebo was 21% with cilostazol 100 mg 2×/day compared to 7% for cilostazol 50 mg 2×/day. Notably, patients in both the 50 mg and 100 mg cilostazol groups showed improvements in global measures of physical functioning compared to placebo-treated patients (p < 0.05) (Strandness et al 1998). Collectively, more than 2,700 IC patients were investigated in eight clinical trials with variable results, but there was a consistent trend toward improvement with cilostazol over placebo. Dawson et al (1998) and Money et al (1998) have shown a significant improvement in maximal walking distance in those who received cilostazol 100 mg 2×/day compared with those who received placebo. Recently, a meta-analysis from six phase III cilostazol trials (Regensteiner et al 2002) with study durations of 12 to 24 weeks found a net benefit of the drug in both the constant workload treadmill and graded treadmill tests. Among the 749 patients who had been evaluated with a constant workload treadmill test, cilostazol 100 mg 2×/day was associated with a 76% improvement in maximal walking distance from the baseline compared with a 20% improvement for placebo (p < 0.0001). Similarly, 895 patients evaluated with a graded treadmill test showed a 40% maximal walking distance improvement with cilostazol 100 mg 2×/day compared with a 20% increase with placebo (p < 0.05) (Figure 4). When data for both types of treadmill protocols were combined, cilostazol 100 mg 2×/day demonstrated superiority over placebo in both maximal walking distance (p < 0.05) and pain-free walking distance values (p < 0.05). Furthermore, cilostazol demonstrated efficacy on several pain and physical dimensions on the Short Form-36 physical functioning scores and Walking Impairment Questionnaire, indicating that the drug’s beneficial effects on exercise capacity are indeed accompanied by meaningful improvements in QoL. The beneficial effects of cilostazol were statistically superior to placebo as early as 4 weeks following treatment onset. However, the therapeutic effects of cilostazol were seen to improve progressively as study duration increased. In clinical practice, 12 to 24 weeks should be expected as a typical waiting period for improvement to occur.


Safety and efficacy of cilostazol in the management of intermittent claudication.

Chi YW, Lavie CJ, Milani RV, White CJ - Vasc Health Risk Manag (2008)

Mean percent change in maximal walking distance (MWD) among intermittent claudication patients receiving cilostazol 100 mg 2×/day (n = 140), cilostazol 50 mg 2×/day (n = 139), or placebo (n = 140) for 24 weeks. Reprinted from Beebe, HG, Dawson DL, Cutler BS, et al 1999. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med, 159:2041–50. Copyright © 1999 with permission from American Medical Association.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2663440&req=5

f3-vhrm-4-1197: Mean percent change in maximal walking distance (MWD) among intermittent claudication patients receiving cilostazol 100 mg 2×/day (n = 140), cilostazol 50 mg 2×/day (n = 139), or placebo (n = 140) for 24 weeks. Reprinted from Beebe, HG, Dawson DL, Cutler BS, et al 1999. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med, 159:2041–50. Copyright © 1999 with permission from American Medical Association.
Mentions: Once the goals of risk factor modification for patients with PAD have been met, the focus of PAD management shifts from general cardio-protection to treatment strategies specific for the clinical manifestations of PAD such as IC. There are consistent data supporting the efficacy of cilostazol for IC. In one the of most important studies included in the agent’s New Drug Application, 698 patients with moderate to severe IC were randomized to a standard dose of cilostazol 100 mg 2×/day, a standard dose of pentoxifylline (400 mg 3×/day), or placebo (3×/day) for a period of 24 weeks. By the end of the study, patients included in the cilostazol group had shown a 54% improvement in maximal walking distance from the baseline compared with increases of 30% in the pentoxifylline group (p < 0.05) and 34% in the placebo group (p < 0.05) (Figure 2) (Dawson et al 2000). Earlier trials have demonstrated a dose-response relationship with cilostazol. In one study (Beebe et al 1999), IC patients who received cilostazol 100 mg 2×/day for 24 weeks increased their maximal walking distance by 51% over the baseline, whereas those who received a 50 mg 2×/day dose showed an increase of only 38% compared to baseline values (p < 0.001 for both doses versus placebo) (Figure 3). In a second trial, the net improvement in maximal walking distance over placebo was 21% with cilostazol 100 mg 2×/day compared to 7% for cilostazol 50 mg 2×/day. Notably, patients in both the 50 mg and 100 mg cilostazol groups showed improvements in global measures of physical functioning compared to placebo-treated patients (p < 0.05) (Strandness et al 1998). Collectively, more than 2,700 IC patients were investigated in eight clinical trials with variable results, but there was a consistent trend toward improvement with cilostazol over placebo. Dawson et al (1998) and Money et al (1998) have shown a significant improvement in maximal walking distance in those who received cilostazol 100 mg 2×/day compared with those who received placebo. Recently, a meta-analysis from six phase III cilostazol trials (Regensteiner et al 2002) with study durations of 12 to 24 weeks found a net benefit of the drug in both the constant workload treadmill and graded treadmill tests. Among the 749 patients who had been evaluated with a constant workload treadmill test, cilostazol 100 mg 2×/day was associated with a 76% improvement in maximal walking distance from the baseline compared with a 20% improvement for placebo (p < 0.0001). Similarly, 895 patients evaluated with a graded treadmill test showed a 40% maximal walking distance improvement with cilostazol 100 mg 2×/day compared with a 20% increase with placebo (p < 0.05) (Figure 4). When data for both types of treadmill protocols were combined, cilostazol 100 mg 2×/day demonstrated superiority over placebo in both maximal walking distance (p < 0.05) and pain-free walking distance values (p < 0.05). Furthermore, cilostazol demonstrated efficacy on several pain and physical dimensions on the Short Form-36 physical functioning scores and Walking Impairment Questionnaire, indicating that the drug’s beneficial effects on exercise capacity are indeed accompanied by meaningful improvements in QoL. The beneficial effects of cilostazol were statistically superior to placebo as early as 4 weeks following treatment onset. However, the therapeutic effects of cilostazol were seen to improve progressively as study duration increased. In clinical practice, 12 to 24 weeks should be expected as a typical waiting period for improvement to occur.

Bottom Line: Besides surgical and endovascular interventions to improve limb-specific outcomes, pharmacotherapy is an effective tool in the treatment of IC.Cilostazol, a Federal Drug Administration-approved medication for the treatment of IC, has demonstrated consistent efficacy in improving exercise capacity and overall health-related QoL.This manuscript will review the pharmacokinetics, safety, and efficacy of cilostazol in the treatment of patients with IC as well as compare this agent with other proven non-invasive therapies for PAD.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Section of Vascular Medicine, Ochsner Health System, 2005 Veterans Blvd., Metairie, LA 70002, USA. ychi@ochsner.org

ABSTRACT
Peripheral arterial disease (PAD) is a major health problem affecting millions of patients worldwide. Many will suffer from intermittent claudication (IC), which leads to marked impairment of quality of life (QoL). Besides surgical and endovascular interventions to improve limb-specific outcomes, pharmacotherapy is an effective tool in the treatment of IC. Cilostazol, a Federal Drug Administration-approved medication for the treatment of IC, has demonstrated consistent efficacy in improving exercise capacity and overall health-related QoL. This manuscript will review the pharmacokinetics, safety, and efficacy of cilostazol in the treatment of patients with IC as well as compare this agent with other proven non-invasive therapies for PAD.

Show MeSH
Related in: MedlinePlus