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Abstract

Background

The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) combined with antiplatelet drugs in patients with peripheral artery disease remain largely unknown.

Objective

The aim of this meta-analysis was to explore the effects of NOACs combined with antiplatelet drugs versus antiplatelet drugs alone in this population.

Methods

A comprehensive search of randomized controlled trials published in PubMed, EMBASE, Web of Science, and the Cochrane Library in 30 September 2020 and before. According to the I² statistic, a random or fixed-effect model was used to analyze the safety and effectiveness of NOACs combined with antiplatelet drugs in peripheral artery disease patients.

Results

Three RCTs met the inclusion criteria, with a total sample size of 11,761 participants. Compared with antiplatelet drugs alone, NOACs combined with antiplatelet drugs resulted in lower risk of ischemic stroke events (OR = 0.75, 95%CI 0.57–0.98, p = 0.03), while other treatment effects were not worse than those of single antiplatelet drugs (p ≥ 0.05). In addition, although compared with single antiplatelet drugs alone, NOACs combined with antiplatelet drugs had a higher risk of major bleeding and clinically related nonmajor bleeding, their risk was not higher for intracranial hemorrhage, which may endanger the life of patients, or for fatal bleeding.

Conclusions

In summary, for peripheral artery disease patients, a combination of NOACs plus antiplatelet drugs may offer additional benefit in reducing ischemic stroke outcome, yet it may increase the risk of bleeding.

Keywords

Anticoagulation therapy antiplatelet therapy atherosclerosis peripheral artery disease

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References

Fowkes

Rudan

, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013; 382: 1329–1340.

Aboyans

Ricco

Bartelink

, et al. ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Endorsed by: the European stroke organization (ESO) the Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J 2017; 39: 763–816.

Welten

Schouten

Hoeks

, et al. Long-term prognosis of patients with peripheral arterial disease: a comparison in patients with coronary artery disease. J Am Coll Cardiol 2008; 51: 1588–1596.

Criqui

Aboyans

Epidemiology of peripheral artery disease. Circ Res 2015; 116: 1509–1526.

Soga

Iida

Takahara

, et al. Two-year life expectancy in patients with critical limb ischemia. JACC Cardiovasc Interv 2014; 7: 1444–1449.

Mahoney

Wang

Keo

, et al. Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States. Circ Cardiovasc Qual Outcomes 2010; 3: 642–651.

Spoorendonk

Krol

Alleman

, et al. The burden of amputation in patients with peripheral arterial disease in the Netherlands. J Cardiovasc Surg 2020; 61: 435–444.

Hirsch

Hartman

Town

, et al. National health care costs of peripheral arterial disease in the Medicare population. Vasc Med 2008; 13: 209–215.

Abola

MTB

Golledge

Miyata

, et al. Asia-Pacific consensus statement on the management of peripheral artery disease: a report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee. J Atheroscler Thromb 2020; 27: 809–907.

10.

Wallentin

Becker

Budaj

, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–1057.

11.

Bonaca

Bhatt

Cohen

, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791–1800.

12.

Gurbel

Tantry

US.

Combination antithrombotic therapies. Circulation 2010; 121: 569–583.

13.

Wiviott

Braunwald

McCabe

, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001–2015.

14.

Sarich

Seltzer

Berkowitz

, et al. Novel oral anticoagulants and reversal agents: considerations for clinical development. Am Heart J 2015; 169: 751–757.

15.

Gurbel

Fox

KAA

Tantry

, et al. Combination antiplatelet and oral anticoagulant therapy in patients with coronary and peripheral artery disease. Circulation 2019; 139: 2170–2185.

16.

McClure

Kaplovitch

Narula

, et al. Rivaroxaban and aspirin in peripheral vascular disease: a review of implementation strategies and management of common clinical scenarios. Curr Cardiol Rep 2019; 21: 115.

17.

Nagy

Kim

Jeong

, et al. Non-vitamin K oral anticoagulants for coronary or peripheral artery disease: a systematic review and meta-analysis of mortality and major bleeding. Minerva Cardioangiol 2019; 67: 477–486.

18.

Bauersachs

Briere

, et al. Antithrombotic treatments in patients with chronic coronary artery disease or peripheral artery disease: a systematic review of randomised controlled trials. Cardiovasc Ther 2020; 2020: 3057168.

19.

Kannel

Dawber

Kagan

, et al. Factors of risk in the development of coronary heart disease – six year follow-up experience. The Framingham Study. Ann Intern Med 1961; 55: 33–50.

20.

Selvin

Erlinger

, et al. 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: 738–743.

21.

Murabito

D’Agostino

Silbershatz

, et al. Intermittent claudication. A risk profile from the Framingham Heart Study. Circulation 1997; 96: 44–49.

22.

Tsai

Vega

GL.

Coronary and peripheral artery plaques: do differences in plaque characteristics translate to differences in lipid management?

J Investig Med 2020; 68: 1141–1151.

23.

Moher

Liberati

Tetzlaff

, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535.

24.

Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.

25.

Anand

Bosch

Eikelboom

, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2018; 391: 219–229.

26.

Bonaca

Bauersachs

Anand

, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med 2020; 382: 1994–2004.

27.

Moll

Baumgartner

Jaff

, et al. Edoxaban plus aspirin vs dual antiplatelet therapy in endovascular treatment of patients with peripheral artery disease: results of the ePAD Trial. J Endovasc Ther 2018; 25: 158–168.

28.

Capell

Bonaca

Nehler

, et al. Rationale and design for the vascular outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD). Am Heart J 2018 May; 199: 83–91.

29.

Schulman

Kearon

, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692–694.

30.

Kaatz

Ahmad

Spyropoulos

, et al. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13: 2119–2126.

31.

Fralick

Colacci

Schneeweiss

, et al. Effectiveness and safety of apixaban compared with rivaroxaban for patients with atrial fibrillation in routine practice: a cohort study. Ann Intern Med 2020; 172: 463–473.

32.

Noseworthy

Yao

Abraham

, et al. Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in nonvalvular atrial fibrillation. Chest 2016; 150: 1302–1312.

33.

Lip

GYH

Keshishian

, et al. Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients. Stroke 2018; 49: 2933–2944.

34.

Rome

Gagne

Avorn

, et al. Non-warfarin oral anticoagulant copayments and adherence in atrial fibrillation: a population-based cohort study. Am Heart J 2021; 233: 109–121.

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Efficacy and safety of non-vitamin K antagonist oral anticoagulants combined with antiplatelet drugs for patients with peripheral artery disease: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background

Objective

Methods

Results

Conclusions

Keywords

Get full access to this article

References

Supplementary Material