Clin Orthop Surg.  2013 Jun;5(2):145-151. 10.4055/cios.2013.5.2.145.

Effects of Beraprost Sodium on Subjective Symptoms in Diabetic Patients with Peripheral Arterial Disease

• Yoon HS
• Choi WJ
• Sung IH
• Lee HS
• Chung HJ
• Lee JW

• KMID: 1705537
• DOI: http://doi.org/10.4055/cios.2013.5.2.145

Abstract

BACKGROUND
This study evaluated the effects of Beraprost sodium (Berasil) on subjective leg symptoms in patients with peripheral arterial disease caused by diabetes mellitus.
METHODS
Ninety-four diabetic patients with peripheral arterial disease were treated with Beraprost in a fixed-dose, prospective, multicenter, cohort study. Beraprost (40 microg) was administered orally 3 times daily (120 microg/day) for 12 weeks. We developed a new disease-specific symptom questionnaire, which evaluated the effect of peripheral arterial disease on leg discomfort in daily life and assessed therapeutic responses to treatment. Patients were asked for their subjective assessment of symptoms on a written questionnaire before treatment and after 12 weeks of therapy.
RESULTS
There was significant improvement in all estimated subjective symptoms (burning, coldness, edema, exertional pain, stabbing, and paresthesias) in the lower extremities at 12 weeks (p < 0.001). There were 18 patients with neuropathy in whom significant improvement was noted for 6 subjective symptoms at 12 weeks (p < 0.05). Adverse events considered to be drug-related were observed in 4 patients (4.3%), all of which were mild and resolved with discontinuation of the medication.
CONCLUSIONS
Beraprost is effective as a treatment for improving various subjective symptoms in the lower extremities, such as burning, coldness, edema, exertional pain, stabbing, and paresthesias, in diabetic patients with peripheral arterial disease.

Keyword

Peripheral arterial disease; Intermittent claudication; Diabetes mellitus; Beraprost sodium; Prostaglandin I2

MeSH Terms

Adult
Aged
Aged, 80 and over
Cohort Studies
Diabetes Complications/*drug therapy/physiopathology
Epoprostenol/*analogs & derivatives/therapeutic use
Female
Humans
Male
Middle Aged
Peripheral Arterial Disease/complications/*drug therapy
Platelet Aggregation Inhibitors/*therapeutic use
Prospective Studies
Statistics, Nonparametric
Epoprostenol
Platelet Aggregation Inhibitors

Reference

1. American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003. 26(12):3333–3341.

2. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc. 1985. 33(1):13–18.

3. Jude EB, Oyibo SO, Chalmers N, Boulton AJ. Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome. Diabetes Care. 2001. 24(8):1433–1437.

4. Vane JR, Botting RM. Pharmacodynamic profile of prostacyclin. Am J Cardiol. 1995. 75(3):3A–10A.

5. Friedman R, Mears JG, Barst RJ. Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. Circulation. 1997. 96(9):2782–2784.

6. Willis AL, Smith DL, Vigo C, Kluge AF. Effects of prostacyclin and orally active stable mimetic agent RS-93427-007 on basic mechanisms of atherogenesis. Lancet. 1986. 2(8508):682–683.

7. Demolis JL, Robert A, Mouren M, Funck-Brentano C, Jaillon P. Pharmacokinetics and platelet antiaggregating effects of beraprost, an oral stable prostacyclin analogue, in healthy volunteers. J Cardiovasc Pharmacol. 1993. 22(5):711–716.

8. Nony P, Ffrench P, Girard P, et al. Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: a study in healthy male subjects. Can J Physiol Pharmacol. 1996. 74(8):887–893.

9. Lièvre M, Morand S, Besse B, Fiessinger JN, Boissel JP. Beraprost et Claudication Intermittente (BERCI) Research Group. Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Circulation. 2000. 102(4):426–431.

10. Mohler ER 3rd, Hiatt WR, Olin JW, Wade M, Jeffs R, Hirsch AT. Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: a double-blinded, randomized, controlled trial. J Am Coll Cardiol. 2003. 41(10):1679–1686.

11. Toyota T, Oikawa S. Beraprost Sodium Study Group. Effects of beraprost sodium (Dorner) in patients with diabetes mellitus complicated by chronic arterial obstruction. Angiology. 2002. 53(1):7–13.

12. Rose GA. The diagnosis of ischaemic heart pain and intermittent claudication in field surveys. Bull World Health Organ. 1962. 27(6):645–658.

13. Taylor LM, Porter JM. Proposed design for a double blinded trial to evaluate medications for treatment of intermittent claudication. J Vasc Surg. 1992. 15(5):882–884.

14. Newman AB, Siscovick DS, Manolio TA, et al. Cardiovascular Heart Study (CHS) Collaborative Research Group. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Circulation. 1993. 88(3):837–845.

15. Criqui MH, Fronek A, Klauber MR, Barrett-Connor E, Gabriel S. The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from noninvasive testing in a defined population. Circulation. 1985. 71(3):516–522.

16. Vogt MT, Cauley JA, Newman AB, Kuller LH, Hulley SB. Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA. 1993. 270(4):465–469.

17. Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975. 1(3):277–299.

18. Krause SJ, Backonja MM. Development of a neuropathic pain questionnaire. Clin J Pain. 2003. 19(5):306–314.

19. Marso SP, Hiatt WR. Peripheral arterial disease in patients with diabetes. J Am Coll Cardiol. 2006. 47(5):921–929.

20. Dawson DL, Cutler BS, Hiatt WR, et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med. 2000. 109(7):523–530.

21. Dawson DL, Cutler BS, Meissner MH, Strandness DE Jr. Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. Circulation. 1998. 98(7):678–686.

22. Beebe HG, Dawson DL, Cutler BS, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med. 1999. 159(17):2041–2050.

23. Belch JJ, Bell PR, Creissen D, et al. Randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent claudication. Circulation. 1997. 95(9):2298–2302.

24. Müller-Bühl U, Diehm C, Krais T, Zimmermann R, Morl H, Eckstein HH. Clinical effects of intravenous iloprost in patients with intermittent claudication. Eur J Clin Pharmacol. 1987. 33(2):127–131.

25. Daousi C, Benbow SJ, Woodward A, MacFarlane IA. The natural history of chronic painful peripheral neuropathy in a community diabetes population. Diabet Med. 2006. 23(9):1021–1024.

26. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006. 29(7):1518–1522.

27. Ziegler D, Rathmann W, Dickhaus T, Meisinger C, Mielck A. KORA Study Group. Prevalence of polyneuropathy in pre-diabetes and diabetes is associated with abdominal obesity and macroangiopathy: the MONICA/KORA Augsburg Surveys S2 and S3. Diabetes Care. 2008. 31(3):464–469.

28. Ziegler D, Rathmann W, Dickhaus T, Meisinger C, Mielck A. KORA Study Group. Neuropathic pain in diabetes, prediabetes and normal glucose tolerance: the MONICA/KORA Augsburg Surveys S2 and S3. Pain Med. 2009. 10(2):393–400.

29. Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract. 2000. 47(2):123–128.

30. Aso Y, Tayama K, Takanashi K, Inukai T, Takemura Y. Changes in skin blood flow in type 2 diabetes induced by prostacyclin: association with ankle brachial index and plasma thrombomodulin levels. Metabolism. 2001. 50(5):568–572.