Oral Beraprost Sodium, a Prostaglandin I 2 Analogue, for Intermittent Claudication : A Double-Blind, Randomized, Multicenter Controlled Trial

Intermittent claudication has been studied in cardiovascular surveys but limited information is available on asymptomatic peripheral arterial disease. The purpose of this paper is to describe the prevalence of both asymptomatic and symptomatic disease and relation to ischaemic heart disease in the Edinburgh Artery Study. A cross-sectional survey was conducted on an age-stratified sample of men and women aged 55 to 74 years selected from age-sex registers in ten general practices in the city. Arterial disease was assessed in 1592 participants by means of the WHO questionnaire on intermittent claudication and measurement of the ankle brachial systolic pressure index (ABPI) and change in ankle systolic pressure during reactive hyperaemia. The prevalence of intermittent claudication was 4.5% (95% confidence interval (CI): 3.5%-5.5%). Major asymptomatic disease causing a significant impairment of blood flow occurred in 8.0% (95% CI: 6.6%-9.4%). A further 16.6% (95% CI: 14.6%-18.5%) had criteria considered abnormal in clinical practice: 9.0% had ABPI less than 0.9 and 7.6% had reactive hyperaemia pressure reduction greater than 20%. Intermittent claudication was equally common in both sexes. The ABPI and reactive hyperaemia results suggested a slight preponderance of asymptomatic disease in males and were consistent with an increasing prevalence with age and lower social class. Mean ABPI was higher in normal men than women, and was lower in the left leg than the right suggesting a unilateral predisposition to disease. Subjects with major asymptomatic disease had more evidence of ischaemic heart disease than in the normal population (relative risk (RR) 1.6; 95% CI: 1.3-1.9).(ABSTRACT TRUNCATED AT 250 WORDS)

This study evaluated the effects of cilostazol on walking distances in patients with intermittent claudication (IC) caused by peripheral arterial occlusive disease. The study was a multicenter, randomized, double-blind, placebo-controlled trial. Two hundred thirty-nine patients with IC were randomly assigned to receive cilostazol (100 mg b.i.d.) or a placebo for 16 weeks. All patients underwent serial, variable-grade, constant-speed treadmill testing. Absolute claudication distance (ACD), assessed at the end of the 12-hour dosing interval (trough), was the primary end point. Secondary end points included ACD assessed 3 to 4 hours after dosing (peak) and initial claudication distances (trough and peak). Functional status measures, including the Medical Outcomes Scale (SF-36) and Walking Impairment Questionnaire, were used to assess subjective changes over the 16-week treatment period. Ankle-brachial indexes were calculated from Doppler-measured systolic pressures at every visit with treadmill testing. Patients treated with cilostazol demonstrated significant improvements over the placebo patients in ACD at all three time points tested after baseline (weeks 8, 12, and 16). Peak treadmill testing at weeks 8 and 12 also showed significant improvement in walking distances for cilostazol-treated patients over placebo-treated patients. At week 16, patients in the cilostazol group had a 96.4-meter (47%) increase in ACD compared with 31.4 meters (12.9%) for the placebo group (p < 0.001). In the SF-36, significant improvement was observed in the physical component subscale and the composite physical component score. In the Walking Impairment Questionnaire, improvements were significant in patient reports of walking speed and specific measures of walking difficulty. Ankle-brachial indexes improved in the cilostazol group (0.64 +/- 0.02 to 0.70 +/- 0.02) compared with the placebo group (0.68 +/- 0.02 to 0.69 +/- 0.02) (p < 0.0125). The most frequent adverse events were headache, abnormal stools (e.g. loose stools), diarrhea, and dizziness. Cilostazol significantly increased ACD at all measured time points and initial claudication distances at most time points. This agent may represent a new treatment option for patients with intermittent claudication.

To review the evidence for efficacy of three contemporary treatments for intermittent claudication: pentoxifylline, exercise programs, and smoking cessation. English-language literature search using MEDLINE, Index Medicus, and bibliographic reviews of major texts and all pertinent articles. For pentoxifylline, randomized, double-blind controlled trials were selected. For exercise, all controlled trials were selected, because few randomized trials have been done. For smoking cessation, 26 pertinent studies were selected after an exhaustive search. Study quality was evaluated; therapeutic efficacy was estimated for pentoxifylline and exercise using meta-analytic techniques. For smoking cessation, all outcomes were determined and described. For pentoxifylline, insufficiently reported data led to marked disparity in effect sizes, preventing a meaningful pooled estimate of effectiveness. The results for exercise therapy suggested that dynamic exercise is beneficial (pooled effect size for pain-free walking distance = 1.03; 95% CI, 0.6 to 1.5; P less than 0.0001). Finally, smoking cessation was associated with a reduced frequency of complications due to progressive disease and improved postoperative graft patency rates. The limited amount and quality of reported data precluded an overall, reliable estimate of pentoxifylline's efficacy. Structured exercise programs increased pain-free walking distance, and smoking cessation improved postoperative graft patency rates and reduced the complications of peripheral arterial disease.