Cilostazol, a type III phosphodiesterase inhibitor, enhances vasodilation and reduces platelet aggregation. Since 1999 when cilostazol was approved for the treatment of intermittent claudication, multiple randomly controlled trials have been done to review its efficacy and safety. Thompson and associates performed a meta-analysis of data from eight multicenter, randomized, double-blind, placebo-controlled trials looking at the safety and efficacy of cilostazol.
All trials included patients 40 years or older with moderate to severe intermittent claudication for at least six months and used exercise treadmill testing to measure patient response to treatment. The pain from claudication had to cause participants to slow the speed of their walking or to stop walking. Patients were excluded from participation if they had ischemic pain at rest or another medical condition that prevented their participation in all phases of the study, or if they were taking more than 81 mg per day of aspirin or more than 1,200 mg per day of ibuprofen, or taking an anticoagulant. Patients in the studies received cilostazol, pentoxifylline, or placebo. The primary end point was maximal walking distance.
In six of the eight trials, cilostazol improved maximal walking distance significantly more than placebo. Pentoxifylline was used in two studies and was not associated with a significant improvement in maximal walking distance. Plasma levels of high-density lipoprotein cholesterol increased by 12.8 percent, and triglyceride levels decreased by 15.8 percent. The physical function subscale of the SF-36 quality-of-life scale revealed significant improvement of perceived physical functioning with cilostazol treatment. The most frequent adverse events noted with cilostazol treatment included headache, diarrhea, abnormal stools, rhinitis, and peripheral edema.
The authors conclude that cilostazol, in a dosage of 50 or 100 mg taken twice daily, significantly increases maximal walking distance and pain-free walking distance when compared with placebo or pentoxifylline. Use of quality-of-life subscales appears to demonstrate improvements in some quality-of-life measures with treatment. There is some advantage to the 100-mg, twice-daily cilostazol dose compared with the 50-mg dose. Both dosages are generally well tolerated. Cessation of cilostazol treatment results in a decline in benefits within several weeks.