Expert Recommendations on Antithrombotic Management of Peripheral Artery Disease: Perspectives from Indian Interventional Radiologists

Abstract

Peripheral artery disease (PAD) imposes a heavy burden of major adverse cardiovascular events (MACE) that are associated with considerable mortality and morbidity and major adverse limb events (MALE) (e.g., thrombectomy, revascularization, amputation) that can substantially impact patients' daily functioning and quality of life. Epidemiological studies have indicated that PAD is an underdiagnosed disease in India, and its associated risk factors remain inadequately controlled. Antithrombotic therapy for PAD is underutilized in India. Revascularization procedures are done in acute or advanced stages. While such invasive strategies are effective in some patients with PAD, these strategies are costly and carry risks, and many patients are not amenable to invasive therapy, especially in low-resource settings like in India. In recent years, dual pathway inhibition (DPI) has emerged as a promising approach to improve the treatment of coronary artery diseases and represented a long-awaited major advancement for the medical treatment of PAD, as demonstrated by the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) and Vascular Outcomes Study of ASA (acetylsalicylic acid) Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER-PAD) trials. DPI with rivaroxaban 2.5 mg twice daily + aspirin 100 mg once daily can be used to decrease the risk of MACE or cerebrovascular events and MALE, in PAD patients without high bleeding risk. Clinical evidence, clinical expertise, and real-world practice were integrated to form expert opinions and a clinical algorithm for using DPI as antithrombotic management in patients with PAD. The expert opinions and algorithms can be adopted not only by interventional radiologists in India involved in the clinical management of patients with PAD but also by vascular surgeons and general practitioners in rural areas, aiming to improve the totality of PAD patient care in India.

Keywords

dual pathway inhibition - revascularization - peripheral artery disease - rivaroxaban - antithrombotic therapy - major adverse limb events

Publikationsverlauf

Artikel online veröffentlicht:
22. Mai 2025

• References

• 1 Krishnan MN, Geevar Z, Mohanan PP, Venugopal K, Devika S. Prevalence of peripheral artery disease and risk factors in the elderly: a community based cross-sectional study from northern Kerala, India. Indian Heart J 2018; 70 (06) 808-815
• 2 Eshcol J, Jebarani S, Anjana RM, Mohan V, Pradeepa R. Prevalence, incidence and progression of peripheral arterial disease in Asian Indian type 2 diabetic patients. J Diabetes Complications 2014; 28 (05) 627-631
• 3 Abola MTB, Golledge J, Miyata T. 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 (08) 809-907
• 4 Song P, Rudan D, Zhu Y. et al. Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis. Lancet Glob Health 2019; 7 (08) e1020-e1030
• 5 Bethel M, Annex BH. Peripheral arterial disease: a small and large vessel problem. Am Heart J Plus 2023; 28: 100291
• 6 Lee J-K, Hsieh I-C, Su C-H. et al. Referral, diagnosis, and pharmacological management of peripheral artery disease: perspectives from Taiwan. Zhonghua Minguo Xinzangxue Hui Zazhi 2023; 39 (01) 97-108
• 7 Bevan GH, White Solaru KT. Evidence-based medical management of peripheral artery disease. Arterioscler Thromb Vasc Biol 2020; 40 (03) 541-553
• 8 Vartanian SM, Conte MS. Surgical intervention for peripheral arterial disease. Circ Res 2015; 116 (09) 1614-1628
• 9 Pai P, Bedi VS, Kamerkar DR. et al. Clinical practice recommendations for antithrombotic management of peripheral artery disease: an Indian perspective. Indian J Vasc Endovasc Surg. 2024; 11: 4
• 10 Khanna NN, Krishna V, Manjunath CN. et al. The Indian consensus statement for the management of lower extremity peripheral artery disease. J Indian Coll Cardiol 2023; 13: S1
• 11 Beckman JA, Schneider PA, Conte MS. Advances in revascularization for peripheral artery disease: revascularization in PAD. Circ Res 2021; 128 (12) 1885-1912
• 12 Espinola-Klein C, Weißer G, Schmitt V, Schwaderlapp M, Munzel T. Antithrombotic therapy in peripheral arterial disease. Front Cardiovasc Med 2022; 9: 927645
• 13 Frank U, Nikol S, Belch J. et al. ESVM Guideline on peripheral arterial disease. Vasa 2019; 48 (Suppl. 102) 1-79
• 14 Gheini A, Shakarami A, Namdari P, Namdari M, Pooria A. Frequency of recurrence of peripheral artery disease among angioplasty and stenting patients. Ann Med Surg (Lond) 2021; 72: 103146
• 15 Gerhard-Herman MD, Gornik HL, Barrett C. et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2017; 135 (12) e686-e725
• 16 Arora E, Regan R, Surendra VU, Arumugam A. Prevalence of peripheral arterial disease among individuals with type 2 diabetes mellitus in India - a systematic review and meta-analysis. Diabetes Metab Syndr 2024; 18 (09) 103124
• 17 Khanna AK, Khanna D, Verma H, Singh T, Tiwary S, Gupta P. A hospital-based population screening for peripheral arterial diseases in a north-east university hospital of India. Indian J Surg 2021; •••: 85
• 18 Gornik HL, Aronow HD, Goodney PP. et al; Writing Committee Members. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2024; 83 (24) 2497-2604
• 19 Diehm C, Allenberg JR, Pittrow D. et al; German Epidemiological Trial on Ankle Brachial Index Study Group. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation 2009; 120 (21) 2053-2061
• 20 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. Circulation 2017; 135 (25) 2534-2555
• 21 Hess CN, Wang TY, Weleski Fu J. et al. Long-term outcomes and associations with major adverse limb events after peripheral artery revascularization. J Am Coll Cardiol 2020; 75 (05) 498-508
• 22 Bonaca MP, Bauersachs RM, Anand SS. et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med 2020; 382 (21) 1994-2004
• 23 Aboyans V, Bauersachs R, Mazzolai L. et al. Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy. Eur Heart J 2021; 42 (39) 4013-4024
• 24 Anand SS, Bosch J, Eikelboom JW. et al; COMPASS Investigators. 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 (10117): 219-229
• 25 Anand SS, Hiatt W, Dyal L. et al. Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials. Eur J Prev Cardiol 2022; 29 (05) e181-e189
• 26 Eikelboom JW, Connolly SJ, Bosch J. et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377 (14) 1319-1330
• 27 Conte MS, Bradbury AW, Kolh P. et al; GVG Writing Group for the Joint Guidelines of the Society for Vascular Surgery (SVS), European Society for Vascular Surgery (ESVS), and World Federation of Vascular Societies (WFVS). Global vascular guidelines on the management of chronic limb-threatening ischemia. Eur J Vasc Endovasc Surg 2019; 58 (1S): S1-S109 , 109.e33
• 28 Hsia JA, Anand S, Nehler MR. et al. Abstract 13474: rivaroxaban reduces major cardiovascular and limb events in patients with the high-risk triad of chronic kidney disease, peripheral artery disease and recent lower extremity revascularization: insights from VOYAGER PAD. Circulation 2020; 142: A13474-A13474
• 29 Krantz M, Hiatt W, Anand S. et al. Efficacy and safety of rivaroxaban in elderly patients with symptomatic pad undergoing revascularization: insights from voyager pad. J Am Coll Cardiol 2021; 77: 1783-1783
• 30 Bhandari N, Newman JD, Berger JS, Smilowitz NR. Diabetes mellitus and outcomes of lower extremity revascularization for peripheral artery disease. Eur Heart J Qual Care Clin Outcomes 2022; 8 (03) 298-306
• 31 American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47 (Suppl. 01) S179-S218
• 32 VOYAGER PAD. Rivaroxaban in PAD with & without Comorbid Diabetes [Internet]. Accessed March 29, 2024 at: https://www.radcliffecardiology.com/video-index/voyager-pad-rivaroxaban-symptomatic-pad-without-comorbid-diabetes
• 33 Bhatt DL, Eikelboom JW, Connolly SJ. et al; COMPASS Steering Committee and Investigators. Role of combination antiplatelet and anticoagulation therapy in diabetes mellitus and cardiovascular disease: insights from the COMPASS trial. Circulation 2020; 141 (23) 1841-1854
• 34 Zhu W, He W, Guo L, Wang X, Hong K. The HAS-BLED score for predicting major bleeding risk in anticoagulated patients with atrial fibrillation: a systematic review and meta-analysis. Clin Cardiol 2015; 38 (09) 555-561
• 35 Visonà A, Zurlo C, Panzavolta C, Gobbo A, Zalunardo B. Bleeding risk in patients with peripheral arterial disease. Life (Basel) 2022; 13 (01) 47
• 36 Basili S, Romiti GF, Cangemi R, Corica B. Lesson learned from the COMPASS and VOYAGER PAD trials: dual pathway inhibition as a new antithrombotic paradigm?. Eur J Prev Cardiol 2022; 29 (05) e178-e180
• 37 Russo V, Fabiani D, Leonardi S. et al. Dual pathway inhibition with rivaroxaban and aspirin reduces inflammatory biomarkers in atherosclerosis. J Cardiovasc Pharmacol 2023; 81 (02) 129-133