Impact of a 4-Week Treatment with Prostaglandin E1 on Health-Related Quality of Life of Patients with Intermittent Claudication

Abstract

Intermittent claudication impairs functional status and quality of life in many patients by limiting walking capacity. The aim of this study was to evaluate the effects of a 4-week treatment with prostaglandin E1 (PGE1), a drug inducing vasodilation and inhibiting platelet aggregation, on improving functional status and health-related quality of life in patients with disabling intermittent claudication. Forty-two untrained outpatients (37 men and five women, mean age 64 +/- 8 years) with intermittent claudication,and maximum walking distance (MWD) of at least 50 and no more than 200 m on treadmill test (5% slope, 3 km/hr) were randomized to 4 weeks of double-blind treatment either with 60 mcg PGE1 daily given IV in 250 mL saline over a period of 2 hours (21 patients) or placebo (250 mL saline, 21 patients). Treatment-free follow-up was completed 8 weeks after the final infusion. Pain free walking distance (PFWD), MWD, and questionnaire evaluation were determined at baseline, after the 4-week treatment period, and at the end of the 8 weeks of the treatment-free follow-up period. After 4 weeks of treatment with PGE1 PFWD and MWD increased from 72 +/- 16 m to 135 +/- 33 m (+87%, p<0.001)and from 140 +/- 30 m to 266 +/- 62 m (+90%, p<0.001), respectively. Analysis of the Walking Impairment Questionnaire responses in the PGE1 group at 4 weeks demonstrated significant improvements in the walking impairment score (+19 percentage points, p<0.001), in the distance score (+25 percentage points, p<0.001), in the speed score (+24 percentage points, p<0.001), in the stair climbing score (+20 percentage points, p<0.001). The RAND survey responses showed improvements in physical function and bodily pain scores (+14 percentage points, p<0.001, and +15 percentage points, p<0.01, respectively). After the treatment-free follow-up period of 8 weeks, increases in PFWD and MWD were maintained (113 +/- 26 m, +57%, p<0.001, and 229 +/- 55 m, +63%, p<0.001, respectively). Similarly, at the end of the treatment-free follow-up, the walking impairment score (+16 percentage points, p<0.001), the distance score (+23 percentage points, p<0.001), the speed score (+22 percentage points, p<0.001), the stair climbing score (+18 percentage points, p<0.001) as well as the RAND physical function and bodily pain scores (+10 percentage points, p<0.001, and +13 percentage points, p<0.01, respectively) were still increased compared with baseline. No change from baseline was found in all the target parameters in the placebo group after 4 weeks of treatment and at the end of the treatment-free follow-up period. These data show that a 4-week treatment with PGE1 improves functional status and quality of life as well as treadmill performance in patients with disabling intermittent claudication as compared with placebo-treated patients. The improvements are also maintained for a period of 8 weeks beyond the end of the treatment. Additional studies are needed to determine the duration of functional benefits after the end of treatment.

ACC/AHA 2005 Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,⁎Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients

“…Vasodilator prostaglandins are considered investigational for this indication, and none have been approved by the FDA for use in patients with PAD. Intravenous administration of PGE-1 and a PGE-1 prodrug once or twice daily for 4 to 8 weeks has been reported to increase pain-free and maximal walking distance in placebo-controlled trials (384)(385)(386)(387). Daily intravenous administrawalking distance by 40% to 60% compared with placebo after 12 to 24 weeks of therapy (161,337,338,369,370).…”

Intravenous alprostadil treatment compared to oral pentoxifylline treatment in outpatients with intermittent claudication – results of a randomised clinical trial

“…Studies in patients with intermittent claudication demonstrated promising increases in walking distance and quality of life with alprostadil, a synthetic form of prostanoid prostaglandin E 1 (PGE 1 ), vs. control treatment [1][2][3][4]. The aim of the present prospective, randomised, active-controlled, multicentre, double-blind study (NCT01263925) was to determine, if alprostadil is superior to pentoxifylline, a common treatment for intermittent claudication at the time of the inception of the study.…”

Quality of life in patients with intermittent claudication

“…Translated versions of the SF-36 were used in Serbian [28], Dutch [16], French [36], Italian [29] and Chinese [39]. Of the 23 studies 5 utilised the RAND-36 tool [1, 4, 5, 30, 33], which contains the same question set as the SF-36 but is analysed differently [18]. The second most common questionnaire used was the Walking Impairment Questionnaire (WIQ) used in 8 out of 31 studies (total 749 patients) [12–14, 19, 30, 33, 38, 42], including a direct comparison by Nicolai et al.…”