症状性下肢动脉疾病抗栓治疗分析

doi:10.3969/j.issn.1004-583X.2021.10.014

摘要/Abstract

摘要：

目的探讨小剂量利伐沙班联合抗血小板药对症状性下肢动脉疾病患者的治疗效果。结论回顾性分析167例下肢动脉粥样硬化病变患者,分为观察组和对照组,观察组为利伐沙班(2.5 mg, 2次/d)联合抗血小板药物西洛他唑(100 mg, 2次/d),对照组单联抗血小板西洛他唑(100 mg, 2次/d)。2组治疗并随访18个月,观察主要肢体不良事件、主要心脑血管事件以及主要出血事件。结果观察组主要心脑血管事件、肢体主要不良事件较对照组明显下降(P<0.05),主要出血事件在两组比较差异无统计学意义(P>0.05)。方法小剂量利伐沙班联合抗血小板药物西洛他唑可明显减少症状性下肢动脉疾病的心脑血管和肢体主要不良事件,改善预后,且具有安全性。

关键词: 动脉粥样硬化, 下肢, 栓塞,胆固醇, 血小板聚集抑制剂

Abstract:

Objective To explore the curative effects of low-dose rivaroxaban combined with ant-platelet drugs for symptomatic lower extremity atherosclerosis disease(LEASD).Methods The data of 167 LEASD patients were retrospectively analyzed and divided into observation group and control group. Patients in observation group were treated with antithrombotic therapy using rivaroxaban (2.5 mg, bid) combined with anti-platelet drug namely cilostazol (100 mg, bid), and those in control group with the same dose of cilostazol alone (100 mg, bid). A 18-month follow-up was performed. The key observation was major adverse limb events(MALEs), major adverse cardiovascular events(MACEs) and adverse bleeding events(MBEs).Results MACEs and MALEs were significantly lower in observation group than in control group (P<0.05). No differences were statistically significant in MBEs between groups (P>0.05).Conclusion For LEASD patient, low-dose rivaroxaban combined with anti-platelet drug namely cilostazol can significantly reduce MACEs and MALEs, and improve prognosis with safety.

Key words: atherosclerosis, lower extremity, embolism,cholesterol, platelet aggregation inhibitors

中图分类号:

R543.5

陈隽, 周一薇, 李秀娟. 症状性下肢动脉疾病抗栓治疗分析[J]. 临床荟萃, 2021, 36(10): 937-941.

Chen Jun, Zhou Yiwei, Li Xiujuan. Analysis of antithrombotic therapy for symptomatic lower extremity atherosclerosis disease[J]. Clinical Focus, 2021, 36(10): 937-941.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2021.10.014

https://huicui.hebmu.edu.cn/CN/Y2021/V36/I10/937

图/表 2

参考文献 32

[1]	Criqui MH, Matsushita K, Aboyans V, et al. Lower extremity peripheral artery disease: Contemporary epidemiology, management gaps, and future directions: A Scientific Statement from the American Heart Association[J]. Circulation, 2021,144(9):171-191.
[2]	Signorelli SS, Marino E, Scuto S, et al. Pathophysiology of peripheral arterial disease (PAD): A review on oxidative disorders[J]. Int J Mol Sci, 2020,21(12):4393. doi: 10.3390/ijms21124393 URL
[3]	Firnhaber JM, Powell CS. Lower extremity peripheral artery disease: Diagnosis and treatment[J]. Am Fam Physician, 2019,99(6):362-369. pmid: 30874413
[4]	Kersting J, Kamper L, Das M, et al. Guideline-oriented therapy of lower extremity peripheral artery disease(PAD)-current data and perspectives[J]. RoFo, 2019,191(4):311-322. doi: 10.1055/a-0690-9365 pmid: 30665251
[5]	Frank U, Nikol S, Belch J, et al. ESVM guideline on peripheral arterial disease[J]. VASA, 2019,48(Suppl 102):1-79.
[6]	Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization[J]. N Engl J Med, 2020,382(21):1994-2004. doi: 10.1056/NEJMoa2000052 URL
[7]	Bartholomew J, Bishop GJ. New treatments for peripheral artery disease[J]. Cleve Clin J Med, 2020,87(5 suppl 1):21-25. doi: 10.3949/ccjm.87.s1.03 URL
[8]	Bhatt DL, Eagle KA, Ohman EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis[J]. JAMA, 2010,304(12):1350-1357. doi: 10.1001/jama.2010.1322 URL
[9]	Le Hello C, Fouillet L, Boulon C, et al. Lower-limb peripheral arterial disease[J]. Rev Med Interne, 2020,41(10):667-672. doi: 10.1016/j.revmed.2020.03.009 URL
[10]	Pradhan AD, Aday AW, Beckman JA. The Big MAC Attack on Peripheral Artery Disease[J]. Circulation, 2020,141(15):1211-1213. doi: 10.1161/CIRCULATIONAHA.120.045627 pmid: 32282252
[11]	Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients[J]. J Thromb Haemost, 2005,3(4):692-694. pmid: 15842354
[12]	Steg PG, Bhatt DL, Wilson PWF, et al. One-year cardiovascular event rates in outpatients with atherothrombosis[J]. JAMA, 2007,297(11):1197-1206. doi: 10.1001/jama.297.11.1197 URL
[13]	Schoenefeld E, Donas K, Radicke A, et al. Perioperative use of aspirin for patients undergoing carotid endarterectomy[J]. Vasa, 2012,41(4):282-287. doi: 10.1024/0301-1526/a000204 pmid: 22825862
[14]	Essa H, Torella F, Lip GYH. Current and emerging drug treatment strategies for peripheral arterial disease[J]. Expert Opin Pharmacother, 2020,21(13):1603-1616. doi: 10.1080/14656566.2020.1774556 URL
[15]	Koksch M, Zeiger F, Wittig K, et al. Coagulation, fibrinolysis and platelet P-selectin expression in peripheral vascular disease[J]. Eur J Vasc Endovasc Surg, 2001,21(2):147-154. doi: 10.1053/ejvs.2000.1294 URL
[16]	Robless PA, Okonko D, Lintott P, et al. Increased platelet aggregation and activation in peripheral arterial disease[J]. Eur J Vasc Endovasc Surg, 2003,25(1):16-22. doi: 10.1053/ejvs.2002.1794 URL
[17]	Cacoub PP, Bhatt DL, Steg PG, et al. Patients with peripheral arterial disease in the CHARISMA trial[J]. Eur Heart J, 2009,30(2):192-201. doi: 10.1093/eurheartj/ehn534 URL
[18]	Liu Y, Shakur Y, Yoshitake M, et al. Cilostazol (pletal): A dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake[J]. Cardiovasc Drug Rev, 2001,19(4):369-386. pmid: 11830753
[19]	Brown T, Forster RB, Cleanthis M, et al. Cilostazol for intermittent claudication[J]. Cochrane Database Syst Rev, 2021, 6(6):CD003748.
[20]	Burleva EP, Korelin SV. Prospects of clinical application of cilostazol for peripheral artery disease[J]. Angiol Sosud Khir, 2020,26(3):28-36. doi: 10.33529/ANGIQ2020304 URL
[21]	Gotoh F, Tohgi H, Hirai S, et al. Cilostazol stroke prevention study: A placebo-controlled double-blind trial for secondary prevention of cerebral infarction[J]. J Stroke Cerebrovasc Dis, 2000,9(4):147-57. doi: 10.1053/jscd.2000.7216 pmid: 24192020
[22]	Shinohara Y, Katayama Y, Uchiyama S, et al. Cilostazol for prevention of secondary stroke(CSPS 2): An aspirin-controlled, double-blind, randomised non-inferiority trial[J]. Lancet Neurol, 2010,9(10):959-968. doi: 10.1016/S1474-4422(10)70198-8 pmid: 20833591
[23]	Katakami N, Kim YS, Kawamori R, et al. The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in subjects with type 2 diabetes mellitus: Principal results of the diabetic atherosclerosis prevention by cilostazol (DAPC) study: A randomized trial[J]. Circulation, 2010,121(23):2584-2591. doi: 10.1161/CIRCULATIONAHA.109.892414 pmid: 20516379
[24]	Lee WH, Chu CY, Hsu PC, et al. Cilostazol for primary prevention of stroke in peripheral artery disease: A population-based longitudinal study in Taiwan[J]. Thromb Res, 2013,132(2) : 190-195. doi: 10.1016/j.thromres.2013.01.036 URL
[25]	EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism[J]. N Engl J Med, 2010,363(26):2499-2510. doi: 10.1056/NEJMoa1007903 URL
[26]	Anand SS, Bosch J, COMPASS Investigators, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: An international, randomised, double-blind, placebo-controlled trial[J]. Lancet, 2018,391(10117):219-229. doi: 10.1016/S0140-6736(17)32409-1 URL
[27]	Anand SS, Caron F, Eikelboom JW, et al. Major adverse limb events and mortality in patients with peripheral artery disease: the COMPASS trial[J]. J Am Coll Cardiol, 2018,71(20):2306-2315. doi: 10.1016/j.jacc.2018.03.008 URL
[28]	Eikelboom JW, Connolly SJ, COMPASS Investigators, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease[J]. N Engl Med, 2017,377(14):1319-1330. doi: 10.1056/NEJMoa1709118 URL
[29]	Bredikhin RA, Krepkogorskiǐ NV, Khaǐrullin RN. Are there alternatives to dual antiplatelet therapy after stenting of peripheral arteries?[J]. Angiol Sosud Khir, 2021,27(3):22-27. Russian. doi: 10.33529/ANGID2021313 URL
[30]	Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome[J]. N Engl J Med, 2012,366(1):9-19. doi: 10.1056/NEJMoa1112277 URL
[31]	Martini R, Andreozzi GM, Deri A, et al. Amputation rate and mortality in elderly patients with critical limb ischemia not suitable for revascularization[J]. Aging Clin Exp Res, 2012,24(3 Suppl):24-27. pmid: 23160502
[32]	Hess CN, Norgren L, Ansel GM, et al. A structured review of antithrombotic therapy in peripheral artery disease with a focus on revascularization: A TASC(InterSociety consensus for the management of peripheral artery disease) initiative[J]. Circulation, 2017,135(25):2534-2555. doi: 10.1161/CIRCULATIONAHA.117.024469 URL

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临床特征	观察组(n=89)	对照组(n=78)	统计值	P值
性别(男/女,例)	65/24	58/20	χ²=0.036	0.850
年龄( $x -$ ±s,岁)	69.3±6.8	68.5±7.2	t=0.738	0.462
BMI(kg/m²)	25.8±5.6	26.1±6.1	t=0.331	0.741
吸烟史(例)	41	33	χ²=0.110	0.740
D-二聚体(mg/L)	2.3±0.3	0.8±0.4	t=20.249	<0.01
ABI	0.6±0.3	0.5±0.4	t=1.841	0.067
高血压病(例)	75	65	χ²=0.002	0.963
SBP(mmHg)	139.31±15.61	143.57±12.91	t=-1.744	0.083
DBP(mmHg)	82.31±7.30	83.06±8.09	t=-0.580	0.563
糖尿病(例)	72	65	χ²=0.043	0.836
空腹血糖(mmol/L)	9.18±1.66	9.41±1.72	t=-0.766	0.445
餐后2小时血糖(mmol/L)	15.10±2.58	15.28±2.71	t=-0.411	0.681
糖化血红蛋白(%)	9.58±2.05	9.48±1.44	t=0.329	0.743
高脂血症(例)	53	51	χ²=0.380	0.538
甘油三酯(mmol/L)	1.91±0.66	2.00±0.57	t=-0.699	0.486
LDL-C(mmol/L)	3.75±1.00	3.67±1.07	t=0.349	0.728
冠心病(例)	35	29	χ²=0.016	0.900
心绞痛发作次数(次/周)	6.26±1.67	5.45±1.55	t=1.994	0.051
心绞痛持续时长(min/次)	2.20±0.96	2.48±1.12	t=-1.085	0.282
慢性心功能衰竭(例)	21	16	χ²=0.085	0.770
NT-proBNP(pg/ml)	2580.13±295.85	2644.21±491.17	t=-0.493	0.625
LVEF(%)	48.62±4.24	50.44±3.08	t=-1.449	0.156
心房颤动(例)	18	12	χ²=0.373	0.541
左心房内径(cm)	4.16±0.37	4.12±0.48	t=0.284	0.779
合并用药
他汀类(例)	49	48	χ²=0.476	0.490
ACEI(例)	73	64	χ²=0.039	0.847
贝前列素(例)	35	28	χ²=0.088	0.767

临床特征	观察组(n=89)	对照组(n=78)	统计值	P值
性别(男/女,例)	65/24	58/20	χ²=0.036	0.850
年龄( $x -$ ±s,岁)	69.3±6.8	68.5±7.2	t=0.738	0.462
BMI(kg/m²)	25.8±5.6	26.1±6.1	t=0.331	0.741
吸烟史(例)	41	33	χ²=0.110	0.740
D-二聚体(mg/L)	2.3±0.3	0.8±0.4	t=20.249	<0.01
ABI	0.6±0.3	0.5±0.4	t=1.841	0.067
高血压病(例)	75	65	χ²=0.002	0.963
SBP(mmHg)	139.31±15.61	143.57±12.91	t=-1.744	0.083
DBP(mmHg)	82.31±7.30	83.06±8.09	t=-0.580	0.563
糖尿病(例)	72	65	χ²=0.043	0.836
空腹血糖(mmol/L)	9.18±1.66	9.41±1.72	t=-0.766	0.445
餐后2小时血糖(mmol/L)	15.10±2.58	15.28±2.71	t=-0.411	0.681
糖化血红蛋白(%)	9.58±2.05	9.48±1.44	t=0.329	0.743
高脂血症(例)	53	51	χ²=0.380	0.538
甘油三酯(mmol/L)	1.91±0.66	2.00±0.57	t=-0.699	0.486
LDL-C(mmol/L)	3.75±1.00	3.67±1.07	t=0.349	0.728
冠心病(例)	35	29	χ²=0.016	0.900
心绞痛发作次数(次/周)	6.26±1.67	5.45±1.55	t=1.994	0.051
心绞痛持续时长(min/次)	2.20±0.96	2.48±1.12	t=-1.085	0.282
慢性心功能衰竭(例)	21	16	χ²=0.085	0.770
NT-proBNP(pg/ml)	2580.13±295.85	2644.21±491.17	t=-0.493	0.625
LVEF(%)	48.62±4.24	50.44±3.08	t=-1.449	0.156
心房颤动(例)	18	12	χ²=0.373	0.541
左心房内径(cm)	4.16±0.37	4.12±0.48	t=0.284	0.779
合并用药
他汀类(例)	49	48	χ²=0.476	0.490
ACEI(例)	73	64	χ²=0.039	0.847
贝前列素(例)	35	28	χ²=0.088	0.767

事件	观察组 (n=89)	对照组 (n=78)	χ²值	P值
心血管死亡	3	6	0.793	0.373
心肌梗死	2	6	1.640	0.200
卒中	2	5	0.907	0.341
主要心血管事件	5	9	4.190	0.041
主要心脑血管事件	6	14	4.953	0.026
血管性截肢	1	7	4.028	0.045
肢体主要不良事件	2	9	4.420	0.036
致死性出血	1	1	0.383	0.536
症状性涉及关键器官的出血	1	1	0.383	0.536
导致住院的出血	2	1	0.013	0.908
主要出血	5	4	0.041	0.839

事件	观察组 (n=89)	对照组 (n=78)	χ²值	P值
心血管死亡	3	6	0.793	0.373
心肌梗死	2	6	1.640	0.200
卒中	2	5	0.907	0.341
主要心血管事件	5	9	4.190	0.041
主要心脑血管事件	6	14	4.953	0.026
血管性截肢	1	7	4.028	0.045
肢体主要不良事件	2	9	4.420	0.036
致死性出血	1	1	0.383	0.536
症状性涉及关键器官的出血	1	1	0.383	0.536
导致住院的出血	2	1	0.013	0.908
主要出血	5	4	0.041	0.839