Analysis of antithrombotic therapy for symptomatic lower extremity atherosclerosis disease

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

Abstract

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

CLC Number:

R543.5

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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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2021.10.014

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

Figures/Tables 2

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

References 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