Effectiveness and Safety of Sarpogrelate Hydrochloride for Peripheral Arterial Disease: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

GAO Wei ¹ , WANG Fang ¹ , LIU Guanjian ² ,  RAN Xingwu ¹

1. Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China;2. Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

RAN Xingwu, Email: ranxingwu@yahoo.com.cn

Keywords：

Peripheral arterial disease; Limb ischemia; Ulcer; Sarpogrelate hydrochloride; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.20120055

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective　 To evaluate the effectiveness and safety of sarpogrelate hydrochloride for patients with peripheral arterial disease (PAD).
Methods　 The randomized controlled trials (RCTs) on PAD treated by sarpogrelate hydrochloride were identified from CBM (1978 to September 2011), CNKI (1979 to May 2011), PubMed (1950 to May 2011), EMbase (1970 to May 2011) and The Cochrane Library (Issue 3, 2011). According to the criteria of the Cochrane Handbook, two reviewers independently screened the studies, extracted and cross-checked the data, and assessed the methodological quality. Then meta-analysis was conducted by using RevMan 5.0 software.
Results　 Nine RCTs involving 522 patients and 532 limbs were included, with low methodological quality in most trials. The results of meta-analyses indicated that compared with the conventional treatment, sarpogrelate hydrochloride could reduce the area of ulcers (MD= –3.22, 95%CI –3.99 to –2.45), and it could increase the ankle-brachial index (SMD=0.49, 95%CI 0.07 to 0.91), blood flow of dorsalis pedis artery (MD=0.16, 95%CI 0.09 to 0.23) and pain-free walking distance (MD=200.87, 95%CI 3.39 to 398.36). Five trials reported the adverse effects of sarpogrelate hydrochloride, most of which were mild gastrointestinal symptoms.
Conclusion　 Based on the review, sarpogrelate hydrochloride may have positive effect on patients with PAD. However, the evidence is not b enough due to the general low methodological quality, so the reliable conclusion has to be drawn with more high quality studies in future.

Citation： GAO Wei,WANG Fang,LIU Guanjian,RAN Xingwu. Effectiveness and Safety of Sarpogrelate Hydrochloride for Peripheral Arterial Disease: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2012, 12(3): 341-346. doi: 10.7507/1672-2531.20120055 Copy

1.	Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation, 2004, 110(6): 738-743.
2.	Guan H, Li YJ, Xu ZR, et al. Prevalence and risk factors of peripheral arterial disease in diabetic patients over 50 years old in China. Chin Med Sci J, 2007, 22(2): 83-88.
3.	王椿, 余婷婷, 王艳, 等. 糖尿病患者下肢动脉病变筛查及危险因素分析. 中国糖尿病杂志, 2007, 15(11): 643-646.
4.	Leng GC, Lee AJ, Fowkes FG, et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. Int J Epidemiol, 1996, 25(6): 1172-1181.
5.	Steg PG, Bhatt DL, Wilson PW, et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA, 2007, 297(11): 1197-1206.
6.	Heald CL, Fowkes FG, Murray GD, et al. Risk of mortality and cardiovascular disease associated with the ankle-brachial index: Systematic review. Atherosclerosis, 2006, 189(1): 61-69.
7.	Barradas MA, Gill DS, Fonseca VA, et al. Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease. Eur J Clin Invest, 1988, 18(4): 399-404.
8.	Hoyer D, Clarke DE, Fozard JR, et al. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev, 1999, 46(2): 157-201.
9.	Nagatomo T, Rashid M, Muntasir HA, et al. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system. Pharmacol Ther, 2004, 104(1): 59-81.
10.	Golino P, Piscione F, Willerson JT, et al. Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med, 1991, 324: 64-68.
11.	Saxena PR, Villalon CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol, 1990, 15 Suppl 7: S17-S34.
12.	Roth BL, Willins DL, Kristiansen K, et al. 5-hydroxytryptamine 2 family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function. Pharmacol Ther, 1998, 79(3): 231-257.
13.	Banes A, Florian JA, Watts SW. Mechanisms of 5-hydroxytryptamine (2A) receptor activation of the mitogen-activated protein kinase pathway in vascular smooth muscle. J Pharmacol Exp Ther, 1999, 291(3): 1179-1187.
14.	Keegan A, Morecroft I, Smillie D, et al. Contribution of the 5-HT(1B) receptor to hypoxia-induced pulmonary hypertension: converging evidence using 5-HT(1B)-receptor knockout mice and the 5-HT(1B/1D)-receptor antagonist GR127935. Circ Res, 2001, 89(12): 1231–1239.
15.	Hara H, Kitajima A, Shimada H, et al. Antithrombic effect of MCI-9042, a new antiplatelet agent on experimental thrombosis models. Thromb Haemost, 1991, 66(4): 484-488.
16.	Yamashita T, Kitamori K, Hashimoto M, et al. Conjunctive effects of 5HT2 receptor antagonist, sarpogrelate, on thrombolysis with modified tissue plasminogen activator in different laser-induced thrombosis models. Haemostasis, 2000, 30(6): 321-332.
17.	Hara H, Osakabe M, Kitajima A, et al. MCI-9042, a new antiplatelet agent is a selective S2-serotonergic receptor antagonist. Thromb Haemost, 1991, 65(4): 415-420.
18.	Nakamura K, Kariyazono H, Moriyama Y, et al. Effects of sarpogrelate hydrochloride on platelet aggregation, and its relation to the release of serotonin and P-selectin. Blood Coagul Fibrinolysis, 1999, 10(8): 513-519.
19.	Sharma SK, Zahradka P, Chapman D, et al. Inhibition of serotonin-induced vascular smooth muscle cell proliferation by sarpogrelate. J Pharmacol Exp Ther, 1999, 290(3): 1475-1481.
20.	Miyazaki M, Higashi Y, Goto C, et al. Sarpogrelate Hydrochloride, a Selective 5-HT2A Antagonist, Improves Vascular Function in Patients With Peripheral Arterial Disease. J Cardiovasc Pharmacol, 2007, 49(4): 221-227.
21.	Higashi Y, Miyazaki M, Goto C, et al. Sarpogrelate Hydrochloride, a Selective Sarpogrelate hydrochloride, a selective 5-hydroxytryptamine (2A) antagonist, augments autologous bone marrow mononuclear cell implantation-induced improvement in endothelium-dependent vasodilation in patients with critical limb ischemia. J Cardiovasc Pharmacol, 2010, 55(1): 56-61.
22.	古川欽一(Furukawa K), 中島光好, 田辺達三ら. 塩酸サルポグレラート(MCI-9042)の慢性動脈閉塞症に対する臨床効果. 臨床医薬, 1991, 7(6): 1206-1226.
23.	宋晓华, 庄舜玖, 戚韶红, 等. 盐酸沙格雷酯治疗下肢动脉硬化性闭塞症的疗效. 药学服务与研究, 2002, 2(2): 97-98.
24.	吴谊青, 初韦江. 盐酸沙格雷酯治疗2型糖尿病下肢血管病变的临床观察. 临床荟萃, 2003, 18(16): 941.
25.	Norgren L, Jawien A, Matyas L, et al. European MCI-9042 Study Group. Sarpogrelate, a 5-hT2A receptor antagonist in intermittent claudication. A phase II European study. Vasc Med, 2006, 11(2): 75-83.
26.	李波, 房泽慧, 张瑛琦. 盐酸沙格雷酯治疗糖尿病足表浅性溃疡30例临床分析. 哈尔滨医药, 2008, 28(5) : 15.
27.	王玉珍, 李翔, 许樟荣, 等. 沙格雷酯与阿司匹林治疗糖尿病下肢血管病变的随机、对照临床研究. 中华内分泌代谢杂志, 2009, 6: 595-597.
28.	吴心池, 施广德, 黄文龙, 等. 沙格雷酯与西洛他唑治疗2型糖尿病下肢血管病变的临床对照研究. 中国糖尿病杂志, 2010, 18(8): 607-610.
29.	Ito K, Notsu T. Effect of sarpogrelate hydrochloride (MCI-9042) on peripheral circulation of chronic arterial occlusive disease. J Clin Ther Med, 1991, 7: 1243-1251.
30.	Nakamura K, Kariyazono H, Masuda H, et al. Effects of sarpogrelate hydrochloride on adenosine diphosphate- or collagen-induced platelet responses in arteriosclerosis obliterans. Blood Coagul Fibrinolysis, 2001, 12(5): 391–397.
31.	许樟荣, 敬华. 糖尿病足国际临床指南. 北京: 人民军医出版社, 2003: 45-47.
32.	Higgins TPT, Altman DG (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins IPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 (updated February 2008). The Cochrane Collaboration, 2008. Available from: www.cochrane-handbook.org.
33.	王晓军, 刘文星, 徐丽梅. 沙格雷酯治疗糖尿病下肢动脉硬化性闭塞症的疗效观察—附58例临床报告. 新医学, 2006, 37(4): 225-227.
34.	Hotta N, Nakamura J, SumitaY, et al. Effects of Anplag, a Selective 5-HT2A Antagonist in diabetic complications. Clin Drug Invest, 1999, 18(3): 199-207.
35.	Shinohara Y, Nishimaru K, Sawada T. Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A Randomized, Double-Blind, Aspirin-Controlled Trial. Strok, 2008, 39(6): 1827-1833.

1. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation, 2004, 110(6): 738-743.
2. Guan H, Li YJ, Xu ZR, et al. Prevalence and risk factors of peripheral arterial disease in diabetic patients over 50 years old in China. Chin Med Sci J, 2007, 22(2): 83-88.
3. 王椿, 余婷婷, 王艳, 等. 糖尿病患者下肢动脉病变筛查及危险因素分析. 中国糖尿病杂志, 2007, 15(11): 643-646.
4. Leng GC, Lee AJ, Fowkes FG, et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. Int J Epidemiol, 1996, 25(6): 1172-1181.
5. Steg PG, Bhatt DL, Wilson PW, et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA, 2007, 297(11): 1197-1206.
6. Heald CL, Fowkes FG, Murray GD, et al. Risk of mortality and cardiovascular disease associated with the ankle-brachial index: Systematic review. Atherosclerosis, 2006, 189(1): 61-69.
7. Barradas MA, Gill DS, Fonseca VA, et al. Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease. Eur J Clin Invest, 1988, 18(4): 399-404.
8. Hoyer D, Clarke DE, Fozard JR, et al. International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev, 1999, 46(2): 157-201.
9. Nagatomo T, Rashid M, Muntasir HA, et al. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system. Pharmacol Ther, 2004, 104(1): 59-81.
10. Golino P, Piscione F, Willerson JT, et al. Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med, 1991, 324: 64-68.
11. Saxena PR, Villalon CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol, 1990, 15 Suppl 7: S17-S34.
12. Roth BL, Willins DL, Kristiansen K, et al. 5-hydroxytryptamine 2 family receptors (5-hydroxytryptamine2A, 5-hydroxytryptamine2B, 5-hydroxytryptamine2C): where structure meets function. Pharmacol Ther, 1998, 79(3): 231-257.
13. Banes A, Florian JA, Watts SW. Mechanisms of 5-hydroxytryptamine (2A) receptor activation of the mitogen-activated protein kinase pathway in vascular smooth muscle. J Pharmacol Exp Ther, 1999, 291(3): 1179-1187.
14. Keegan A, Morecroft I, Smillie D, et al. Contribution of the 5-HT(1B) receptor to hypoxia-induced pulmonary hypertension: converging evidence using 5-HT(1B)-receptor knockout mice and the 5-HT(1B/1D)-receptor antagonist GR127935. Circ Res, 2001, 89(12): 1231–1239.
15. Hara H, Kitajima A, Shimada H, et al. Antithrombic effect of MCI-9042, a new antiplatelet agent on experimental thrombosis models. Thromb Haemost, 1991, 66(4): 484-488.
16. Yamashita T, Kitamori K, Hashimoto M, et al. Conjunctive effects of 5HT2 receptor antagonist, sarpogrelate, on thrombolysis with modified tissue plasminogen activator in different laser-induced thrombosis models. Haemostasis, 2000, 30(6): 321-332.
17. Hara H, Osakabe M, Kitajima A, et al. MCI-9042, a new antiplatelet agent is a selective S2-serotonergic receptor antagonist. Thromb Haemost, 1991, 65(4): 415-420.
18. Nakamura K, Kariyazono H, Moriyama Y, et al. Effects of sarpogrelate hydrochloride on platelet aggregation, and its relation to the release of serotonin and P-selectin. Blood Coagul Fibrinolysis, 1999, 10(8): 513-519.
19. Sharma SK, Zahradka P, Chapman D, et al. Inhibition of serotonin-induced vascular smooth muscle cell proliferation by sarpogrelate. J Pharmacol Exp Ther, 1999, 290(3): 1475-1481.
20. Miyazaki M, Higashi Y, Goto C, et al. Sarpogrelate Hydrochloride, a Selective 5-HT2A Antagonist, Improves Vascular Function in Patients With Peripheral Arterial Disease. J Cardiovasc Pharmacol, 2007, 49(4): 221-227.
21. Higashi Y, Miyazaki M, Goto C, et al. Sarpogrelate Hydrochloride, a Selective Sarpogrelate hydrochloride, a selective 5-hydroxytryptamine (2A) antagonist, augments autologous bone marrow mononuclear cell implantation-induced improvement in endothelium-dependent vasodilation in patients with critical limb ischemia. J Cardiovasc Pharmacol, 2010, 55(1): 56-61.
22. 古川欽一(Furukawa K), 中島光好, 田辺達三ら. 塩酸サルポグレラート(MCI-9042)の慢性動脈閉塞症に対する臨床効果. 臨床医薬, 1991, 7(6): 1206-1226.
23. 宋晓华, 庄舜玖, 戚韶红, 等. 盐酸沙格雷酯治疗下肢动脉硬化性闭塞症的疗效. 药学服务与研究, 2002, 2(2): 97-98.
24. 吴谊青, 初韦江. 盐酸沙格雷酯治疗2型糖尿病下肢血管病变的临床观察. 临床荟萃, 2003, 18(16): 941.
25. Norgren L, Jawien A, Matyas L, et al. European MCI-9042 Study Group. Sarpogrelate, a 5-hT2A receptor antagonist in intermittent claudication. A phase II European study. Vasc Med, 2006, 11(2): 75-83.
26. 李波, 房泽慧, 张瑛琦. 盐酸沙格雷酯治疗糖尿病足表浅性溃疡30例临床分析. 哈尔滨医药, 2008, 28(5) : 15.
27. 王玉珍, 李翔, 许樟荣, 等. 沙格雷酯与阿司匹林治疗糖尿病下肢血管病变的随机、对照临床研究. 中华内分泌代谢杂志, 2009, 6: 595-597.
28. 吴心池, 施广德, 黄文龙, 等. 沙格雷酯与西洛他唑治疗2型糖尿病下肢血管病变的临床对照研究. 中国糖尿病杂志, 2010, 18(8): 607-610.
29. Ito K, Notsu T. Effect of sarpogrelate hydrochloride (MCI-9042) on peripheral circulation of chronic arterial occlusive disease. J Clin Ther Med, 1991, 7: 1243-1251.
30. Nakamura K, Kariyazono H, Masuda H, et al. Effects of sarpogrelate hydrochloride on adenosine diphosphate- or collagen-induced platelet responses in arteriosclerosis obliterans. Blood Coagul Fibrinolysis, 2001, 12(5): 391–397.
31. 许樟荣, 敬华. 糖尿病足国际临床指南. 北京: 人民军医出版社, 2003: 45-47.
32. Higgins TPT, Altman DG (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins IPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 (updated February 2008). The Cochrane Collaboration, 2008. Available from: www.cochrane-handbook.org.
33. 王晓军, 刘文星, 徐丽梅. 沙格雷酯治疗糖尿病下肢动脉硬化性闭塞症的疗效观察—附58例临床报告. 新医学, 2006, 37(4): 225-227.
34. Hotta N, Nakamura J, SumitaY, et al. Effects of Anplag, a Selective 5-HT2A Antagonist in diabetic complications. Clin Drug Invest, 1999, 18(3): 199-207.
35. Shinohara Y, Nishimaru K, Sawada T. Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A Randomized, Double-Blind, Aspirin-Controlled Trial. Strok, 2008, 39(6): 1827-1833.

Chinese Journal of Evidence-Based Medicine

Effectiveness and Safety of Sarpogrelate Hydrochloride for Peripheral Arterial Disease: A Systematic Review

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content