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Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial
Open accessAbstract
Background Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.Methods This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.Findings Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).Interpretation Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.Funding Bayer AG.
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“A study shared that low-dose rivaroxaban with aspirin reduced major adverse cardiovascular and limb events compared with aspirin alone without significantly increasing major bleeding [82].”
From Revascularization Strategies for Acute and Chronic Mesenteric Ischemia: A Narrative Review (2024) · cites this paper as [82]
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“There was an associated increased risk of bleeding with rivaroxaban, although no significant excess in fatal bleeding was noted.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [58]
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“a review of 56 studies including patients with diabetes suggested higher limbsalvage rates after revascularization (78-85% at 1 year) compared with conservative management.768”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [768]
In the citing paper
“The risk of major adverse cardiovascular events (MACEs) was significantly lower with the combination of rivaroxaban plus aspirin compared with either aspirin alone or rivaroxaban alone.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [58]
In the citing paper
“The ischemic benefits of rivaroxaban were consistent in the subgroup with diabetes mellitus, suggesting that low-dose anticoagulation added to antiplatelet therapy may be another option for secondary prevention in patients with T2DM and stable CAD.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [58]
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Self-citationCirculating Biomarkers in Lower Extremity Artery Disease
Ziegler, L., Hedin, U., & Gottsäter, A. (2022) · European Cardiology Review · doi:10.15420/ecr.2021.58 · Cited by 16
Current Management of Peripheral Artery Disease: Focus on Pharmacotherapy
Golledge, J., Fernando, M. E., & Armstrong, D. G. (2022) · Drugs · doi:10.1007/s40265-022-01755-7 · Cited by 15
“80) in 7470 patients with PAD or carotid artery disease (Table 3) [67].”
BackgroundSelf-citationComparative Effectiveness and Safety of Direct Oral Anticoagulants: Overview of Systematic Reviews
Raschi, E., Bianchin, M., Gatti, M., Squizzato, A., & Ponti, F. D. (2019) · Drug Safety · doi:10.1007/s40264-019-00866-7 · Cited by 14
Petersohn, S., Pouwels, X., Ramaekers, B. L. T., ten Cate‐Hoek, A. J., & Joore, M. A. (2020) · European Journal of Preventive Cardiology · doi:10.1177/2047487320913380 · Cited by 14
“Rivaroxaban is a selective oral factor Xa inhibitor that can be taken in combination with aspirin for cardiovascular risk reduction in patients with a history of cardiovascular disease.(1) The COMPASS trial assessed the effectiveness of dual pathway inhibition (DPI) with rivaroxaban 2.”
BackgroundMethodInfluentialPeripheral Artery Disease in the Legs
McDermott, M. M. (2026) · New England Journal of Medicine · doi:10.1056/nejmcp2501200 · Cited by 15
Verdoia, M., Kedhi, E., Suryapranata, H., & Luca, G. D. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.02.011 · Cited by 13
Atherosclerosis and Atrial Fibrillation: Double Trouble
Abolbashari, M. (2022) · Current Cardiology Reports · doi:10.1007/s11886-021-01625-w · Cited by 13
The role of long non-coding RNA in abdominal aortic aneurysm
Xu, Y., Yang, S., & Xue, G. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1153899 · Cited by 13
“In addition to these effects, ROS directly activates MMPs (Anand et al., 2018) and inhibits the MMP inhibitor plasminogen activator inhibitor type 1 (PAI-1) (Bobadilla et al.”
BackgroundInfluentialArmario, P., Brotons, C., Elosúa, R., de Leciñana, M. A., Castro, A., Clarà, A. B. I., Cortés, O., Rodríguez, Á. D., Herranz, M., Justo, S., et al. (2020) · Hipertensión y Riesgo Vascular · doi:10.1016/j.hipert.2020.07.004 · Cited by 13
Normahani, P., Epstein, D. M., Gaggero, A., Davies, A. H., Sounderajah, V., & Jaffer, U. (2021) · Annals of Surgery · doi:10.1097/sla.0000000000004815 · Cited by 13
Li, X., Zhang, X., Jin, Q., Xue, Y., Lu, W., Ge, J., Zhou, D., & Lv, Q. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.614762 · Cited by 13
“Xa inhibitor that can selectively inhibit FXa and has a rapid onset of action, which could help prevent thrombosis and platelet aggregation (Anand et al., 2018; Petzold et al., 2020).”
BackgroundSelf-citationLee, J., Hsieh, C., Su, C.-H., Huang, H., Lei, M., Chiu, K., Huang, C.-L., Chen, C., Hsu, P., Hsu, C., et al. (2023) · PubMed Central · doi:10.6515/acs.202301_39(1).20220815a · Cited by 14
Pharmacological interventions for asymptomatic carotid stenosis
Clezar, C. N., Flumignan, C. D. Q., Cassola, N., Nakano, L. C. U., Trevisani, V. F. M., & Flumignan, R. L. (2023) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd013573.pub2 · Cited by 13
Arps, K. E., Rifai, M. A., Blaha, M. J., Michos, E. D., Nasir, K., Yeboah, J., Budoff, M. J., Blumenthal, R. S., Bittencourt, M. S., & McEvoy, J. W. (2019) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2019.07.016 · Cited by 13
LDL Cholesterol and Ischemic Stroke in Patients with Nonvalvular Atrial Fibrillation
Omelchenko, A., Hornik‐Lurie, T., Gabay, H., Minha, S., Assali, A., & Pereg, D. (2020) · The American Journal of Medicine · doi:10.1016/j.amjmed.2020.08.035 · Cited by 14
Colledanchise, K. N., Mantella, L. E., Hétu, M., Liblik, K., Abunassar, J. G., & Johri, A. M. (2021) · International journal of cardiac imaging · doi:10.1007/s10554-021-02334-9 · Cited by 13
Current and Novel Emerging Medical Therapies for Peripheral Artery Disease: A Literature Review
Arabzadeh, A., Faghfuri, E., Soofiyani, S. R., Abdolahinia, E. D., Siapush, S., Nejati‐Koshki, K., Shahrami, B., Asghariazar, V., & Pahlavan, Y. (2022) · Advanced Pharmaceutical Bulletin · doi:10.34172/apb.2023.025 · Cited by 13
The Attributable Risk of Nonstenotic Cervical Carotid Plaque in Cryptogenic Embolic Stroke
Siegler, J. E. (2023) · Stroke Vascular and Interventional Neurology · doi:10.1161/svin.122.000727 · Cited by 12
“…aspirin and low-dose rivaroxaban (2.5 mg twice daily) was recently shown to be more effective than aspirin alone at reducing cardiovascular events 82 and stroke 83 in patients with stable peripheral artery disease (including asymptomatic ICA stenosis > 50%), in the Cardio-vascular Outcomes for…”
InfluentialWang, B., Liu, H., Zhang, S., Cheng, A., Yan, C., Xu, B., & Gao, Y. (2023) · Drug Delivery and Translational Research · doi:10.1007/s13346-023-01343-6 · Cited by 12
“Aspirin is a first-line antiplatelet aggregation drug and is considered the most cost-effective drug for secondary prevention of coronary artery disease [1].”
BackgroundCurrent and emerging drug treatment strategies for peripheral arterial disease
Essa, H., Torella, F., & Lip, G. Y. H. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1774556 · Cited by 12
“The utility of Rivaroxaban in PAD was first demonstrated in 2017 in the COMPASS trial (Cardiovascular outcomes for people using anticoagulation strategies) [65].”
BackgroundHernández, D., Vázquez, T., Armas-Padrón, A. M., Alonso-Titos, J., Casas, C., Gutiérrez, E., Jironda, C., Cabello, M., & López, V. (2020) · Transplantation · doi:10.1097/tp.0000000000003518 · Cited by 12
“118,119 In addition, a suitable diet and lifestyle with anti-inflammatory properties could decrease inflammation-related CVD and improve arterial stiffness.”
Petersohn, S., Grimm, S. E., Ramaekers, B. L. T., ten Cate‐Hoek, A. J., & Joore, M. A. (2021) · Value in Health · doi:10.1016/j.jval.2021.01.004 · Cited by 13
Gouda, P., Ramasundarahettige, C. F., Anand, S. S., Muhlhoffer, E., Berkowitz, S. D., Fox, K. A. A., Eikelboom, J. W., & Welsh, R. C. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.07.003 · Cited by 12
Self-citationBhagirath, V. C., Nash, D., Wan, D., & Anand, S. S. (2022) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2022.02.004 · Cited by 13
Self-citationAntithrombotika und Antihämorrhagika
Hein, L., & Wille, H. (2019) · Springer eBooks · doi:10.1007/978-3-662-59046-1_19 · Cited by 12
Antiplatelet therapy for peripheral artery disease
Melfi, R., & Ricottini, E. (2018) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt.2018.07.02 · Cited by 12
Identifying asymptomatic patients at high-risk for stroke
Gaba, K., & Bulbulia, R. A. (2019) · The Journal of Cardiovascular Surgery · doi:10.23736/s0021-9509.19.10912-3 · Cited by 12
Chen, C., Kan, Y., Shi, Z., Guo, D., Fu, W., Li, Y., Lv, Q., Li, X., & Si, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.608247 · Cited by 12
“The subjects included 21,086 ACS patients (Mega et al., 2009; Mega et al., 2012; Ohman et al., 2017), 29,846 stable CAD patients (Connolly et al., 2018; Zannad et al., 2018), and 14,043 PAD patients (Anand et al., 2018; Bonaca et al., 2020), and the mean or median age was 57 through 68 years old.”
BackgroundMethodResultInfluentialAntithrombotic Treatment in Lower Extremity Peripheral Arterial Disease
Gottsäter, A. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.773214 · Cited by 14
A Bon VOYAGER for Peripheral Artery Disease
Creager, M. A. (2020) · New England Journal of Medicine · doi:10.1056/nejme2007274 · Cited by 13
Hou, B., Gang, Q., Li, X., Yu, L., Jiang, H., Shen, S., Xin, S., & Zhang, J. (2024) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2024.01.205 · Cited by 12
Self-citationChinese expert consensus on anti-thrombotic therapy for pan-vascular diseases (2023 edition)
Chinese College of Cardiovascular Physicians (2024) · Cardiology Plus · doi:10.1097/cp9.0000000000000079 · Cited by 12
Yuan, Ž., Levitan, B. S., Deng, H., Szarek, M. J., Bauersachs, R. M., Berkowitz, S. D., Haskell, L. P., Barnathan, E. S., & Bonaca, M. P. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.123.032782 · Cited by 11
“14 However, the data associated with re-vascularization in this subpopulation were limited.”
InfluentialRamacciotti, E., & Weitz, J. I. (2019) · Thrombosis Research · doi:10.1016/j.thromres.2019.09.033 · Cited by 11
Poredoš, P., Blinc, A., Novo, S., & Antignani, P. L. (2021) · International Angiology · doi:10.23736/s0392-9590.20.04518-6 · Cited by 11
Bonaca, M. P., Antman, E. M., Cunningham, J. W., Wiviott, S. D., Murphy, S. A., Halperin, J. L., Weitz, J. I., GROSSO, M. A., Lanz, H., Braunwald, E., et al. (2021) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvab089 · Cited by 12
Gioscia, R., Castagno, C., Verdoia, M., Conti, B., Forliti, E., & Rognoni, A. (2023) · World Journal of Cardiology · doi:10.4330/wjc.v15.i4.142 · Cited by 12
Lower extremity arterial disease perspective: IUA consensus document on "lead management". Part 1
Antignani, P. L., Gargiulo, M., Gastaldi, G., Jawień, A., Mansilha, A., & Poredoš, P. (2023) · International Angiology · doi:10.23736/s0392-9590.23.05110-6 · Cited by 12
Harky, A., Maskell, P., & Burgess, M. (2018) · Vascular · doi:10.1177/1708538118818622 · Cited by 11
“Anand et al.52 later published a sub-group analysis of patients with PAD in the COMPASS trial.”
BackgroundResultInfluentialAntithrombotic treatment of asymptomatic carotid atherosclerosis: a medical dilemma
Gresele, P., Paciullo, F., & Migliacci, R. (2020) · Internal and Emergency Medicine · doi:10.1007/s11739-020-02347-7 · Cited by 12
Antithrombotic Treatment for Peripheral Arterial Occlusive Disease
Hardung, D., Behne, A., Boral, M., Giesche, C., & Langhoff, R. (2021) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.m2021.0157 · Cited by 12
Effect of combining aspirin and rivaroxaban on atherosclerosis in mice
Grover, S. P., Coughlin, T. M., Fleifil, S., Posma, J., Spronk, H. M. H., Heitmeier, S., Owens, A. P., & Mackman, N. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.02.010 · Cited by 12
Antithrombotic therapy in peripheral arterial disease
Espinola–Klein, C., Weißer, G., Schmitt, V. H., Schwaderlapp, M., & Münzel, T. F. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.927645 · Cited by 10
Gaddi, A. V., Capello, F., Fronea, O. F. G., Fadda, S., & Darabont, R. (2020) · JRSM Cardiovascular Disease · doi:10.1177/2048004020907002 · Cited by 10
“However, there is no evidence that these drugs can improve the walking distance in IC, while an augmented risk of bleeding was reported for the latter.(21) Nevertheless, for patients with IC, symptom relief represents an important therapeutic goal.”
BackgroundThe impact of chronic kidney disease on outcomes following peripheral vascular intervention
Narcisse, D. I., Weissler, E. H., Rymer, J. A., Armstrong, E. J., Secemsky, E. A., Gray, W. A., Mustapha, J. A., Adams, G. L., Ansel, G. M., Patel, M. R., et al. (2020) · Clinical Cardiology · doi:10.1002/clc.23444 · Cited by 9
“These patients may benefit more from aggressive medical management with high-intensity statins and/or PCSK9 inhibitors, more aggressive control of diabetes mellitus with GLP-1 and/or SGLT2 inhibitors, and more aggressive antiplatelet or antithrombotic medications (including rivaroxaban as demonstrated in the COMPASS t…”
BackgroundLuca, L. D., Bonaca, M. P., & Magnani, G. (2020) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2020.1833719 · Cited by 15
García-Escobar, I., Brozos-Vázquez, E., Abad, D. G., Martínez-Marín, V., Pachón, V., & Martín, A. J. M. (2020) · Clinical & Translational Oncology · doi:10.1007/s12094-020-02506-4 · Cited by 11
“Coadministration with ASA is indicated for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events [28].”
Background
Metadata
- Authors
- Anand, S. S., Bosch, J., Eikelboom, J. W., Connolly, S. J., Diaz, R., Widimsky, P., Aboyans, V., Alings, M., Kakkar, A. K., Keltai, K., Maggioni, A. P., Lewis, B. S., Störk, S., Zhu, J., Lopez-Jaramillo, P., O'Donnell, M., Commerford, P. J., Vinereanu, D., Pogosova, N., Ryden, L., Fox, K. A. A., Bhatt, D. L., Misselwitz, F., Varigos, J. D., Vanassche, T., Avezum, A. A., Chen, E., Branch, K., Leong, D. P., Bangdiwala, S. I., Hart, R. G., Yusuf, S., SALA, J., CARTASEGNA, L., VICO, M., HOMINAL, M. A., HASBANI, E., CACCAVO, A., ZAIDMAN, C., VOGEL, D., HRABAR, A., SCHYGIEL, P. O., CUNEO, C., LUQUEZ, H., MACKINNON, I. J., AHUAD GUERRERO, R. A., COSTABEL, J. P., BARTOLACCI, I. P., MONTANA, O., BARBIERI, M., GOMEZ VILAMAJO, O., GARCIA DURAN, R. O., SCHIAVI, L. B., GARRIDO, M., INGARAMO, A., BORDONAVA, A. P., PELAGAGGE, M. J., NOVARETTO, L., ALBISU DI GENNERO, J. P., IBANEZ SAGGIA, L. M., ALVAREZ, M., VITA, N. A., MACIN, S. M., DRAN, R. D., CARDONA, M., GUZMAN, L., SARJANOVICH, R. J., CUADRADO, J., NANI, S., LITVAK BRUNO, M. R., CHACON, C., MAFFEI, L. E., GRINFELD, D., VENSENTINI, N., MAJUL, C. R., LUCIARDI, H. L., GONZALEZ COLASO, P. D. C., FERRE PACORA, F. A., VAN DEN HEUVEL, P., VERHAMME, P., ECTOR, B., DEBONNAIRE, P., VAN DE BORNE, P., LEROY, J., SCHROE, H., VRANCKX, P., ELEGEERT, I., HOFFER, E., DUJARDIN, K., INDIO DO BRASIL, C., PRECOMA, D., ABRANTES, J. A., MANENTI, E., REIS, G., SARAIVA, J., MAIA, L., HERNANDES, M., ROSSI, P., ROSSI DOS SANTOS, F., ZIMMERMANN, S. L., RECH, R., ABIB JR, E., LEAES, P., BOTELHO, R., DUTRA, O., SOUZA, W., BRAILE, M., IZUKAWA, N., NICOLAU, J. C., TANAJURA, L. F., SERRANO JUNIOR, C. V., MINELLI, C., NASI, L. A., OLIVEIRA, L., DE CARVALHO CANTARELLI, M. J., TYTUS, R., PANDEY, S., LONN, E., CHA, J., VIZEL, S., BABAPULLE, M., LAMY, A., SAUNDERS, K., BERLINGIERI, J., KIAII, B., BHARGAVA, R., MEHTA, P., HILL, L., FELL, D., LAM, A., AL-QOOFI, F., BROWN, C., PETRELLA, R., RICCI, J. A., GLANZ, A., NOISEUX, N., BAINEY, K., MERALI, F., HEFFERNAN, M., DELLA SIEGA, A., DAGENAIS, G. R., DAGENAIS, F., BRULOTTE, S., NGUYEN, M., HARTLEIB, M., GUZMAN, R., BOURGEOIS, R., RUPKA, D., KHAYKIN, Y., GOSSELIN, G., HUYNH, T., PILON, C., CAMPEAU, J., PICHETTE, F., DIAZ, A., JOHNSTON, J., SHUKLE, P., HIRSCH, G., RHEAULT, P., CZARNECKI, W., ROY, A., NAWAZ, S., FREMES, S., SHUKLA, D., JANO, G., COBOS, J. L., CORBALAN, R., MEDINA, M., NAHUELPAN, L., RAFFO, C., PEREZ, L., POTTHOFF, S., STOCKINS, B., SEPULVEDA, P., PINCETTI, C., VEJAR, M., TIAN, H., WU, X., KE, Y., JIA, K., YIN, P., WANG, Z., YU, L., WU, S., WU, Z., LIU, S. W., BAI, X. J., ZHENG, Y., YANG, P., YANG, Y. M., ZHANG, J., GE, J., CHEN, X. P., LI, J., HU, T. H., ZHANG, R., ZHENG, Z., CHEN, X., TAO, L., LI, J., HUANG, W., FU, G., LI, C., DONG, Y., WANG, C., ZHOU, X., KONG, Y., SOTOMAYOR, A., ACCINI MENDOZA, J. L., CASTILLO, H., URINA, M., AROCA, G., PEREZ, M., MOLINA DE SALAZAR, D. I., SANCHEZ VALLEJO, G., FERNANDO, M. J., GARCIA, H., GARCIA, L. H., ARCOS, E., GOMEZ, J., CUERVO MILLAN, F., TRUJILLO DADA, F. A., VESGA, B., MORENO SILGADO, G. A., ZIDKOVA, E., LUBANDA, J.-C., KALETOVA, M., KRYZA, R., MARCINEK, G., RICHTER, M., SPINAR, J., MATUSKA, J., TESAK, M., MOTOVSKA, Z., BRANNY, M., MALY, J., MALY, M., WIENDL, M., FOLTYNOVA CAISOVA, L., SLABY, J., VOJTISEK, P., PIRK, J., SPINAROVA, L., BENESOVA, M., CANADYOVA, J., HOMZA, M., FLORIAN, J., POLASEK, R., COUFAL, Z., SKALNIKOVA, V., BRAT, R., BRTKO, M., JANSKY, P., LINDNER, J., MARCIAN, P., STRAKA, Z., TRETINA, M., DUARTE, Y. C., POW CHON LONG, F., SANCHEZ, M., LOPEZ, J., PERUGACHI, C., MARMOL, R., TRUJILLO, F., TERAN, P., TUOMILEHTO, J., TUOMILEHTO, H., TUOMINEN, M.-L., TUOMILEHTO, H., KANTOLA, I., STEG, G., ABOYANS, V., LECLERCQ, F., FERRARI, E., BOCCARA, F., MESSAS, E., MISMETTI, P., SEVESTRE, M. A., CAYLA, G., MOTREFF, P., STOERK, S., DUENGEN, H.-D., STELLBRINK, C., GUEROCAK, O., KADEL, C., BRAUN-DULLAEUS, R., JESERICH, M., OPITZ, C., VOEHRINGER, H.-F., APPEL, K.-F., WINKELMANN, B., DORSEL, T., NIKOL, S., DARIUS, H., RANFT, J., SCHELLONG, S., JUNGMAIR, W., DAVIERWALA, P., VORPAHL, M., BAJNOK, L., LASZLO, Z., NOORI, E., VERESS, G., VERTES, A., ZSARY, A., KIS, E., KORANYI, L., BAKAI, J., BODA, Z., POOR, F., JARAI, Z., KEMENY, V., BARTON, J., MCADAM, B., MURPHY, A., CREAN, P., MAHON, N., CURTIN, R., MACNEILL, B., DINNEEN, S., HALABI, M., ZIMLICHMAN, R., ZELTSER, D., TURGEMAN, Y., KLAINMAN, E., LEWIS, B., KATZ, A., ATAR, S., ZIMLICHMAN, R., NIKOLSKY, E., BOSI, S., NALDI, M., FAGGIANO, P., ROBBA, D., MOS, L., SINAGRA, G., COSMI, F., OLTRONA VISCONTI, L., CARMINE, D. M., DI PASQUALE, G., DI BIASE, M., MANDORLA, S., BERNARDINANGELI, M., PICCINNI, G. C., GULIZIA, M. M., GALVANI, M., VENTURI, F., MOROCUTTI, G., BALDIN, M. G., OLIVIERI, C., PERNA, G. P., CIRRINCIONE, V., KANNO, T., DAIDA, H., OZAKI, Y., MIYAMOTO, N., HIGASHIUE, S., DOMAE, H., HOSOKAWA, S., KOBAYASHI, H., KURAMOCHI, T., FUJII, K., MIZUTOMI, K., SAKU, K., KIMURA, K., HIGUCHI, Y., ABE, M., OKUDA, H., NODA, T., MITA, T., HIRAYAMA, A., ONAKA, H., INOKO, M., HIROKAMI, M., OKUBO, M., AKATSUKA, Y., IMAMAKI, M., KAMIYA, H., MANITA, M., HIMI, T., UENO, H., HISAMATSU, Y., AKO, J., NISHINO, Y., KAWAKAMI, H., YAMADA, Y., KORETSUNE, Y., YAMADA, T., YOSHIDA, T., SHIMOMURA, H., KINOSHITA, N., TAKAHASHI, A., YUSOFF, K., WAN AHMAD, W. A., ABU HASSAN, M. R., KASIM, S., ABDUL RAHIM, A. A., MOHD ZAMRIN, D., MACHIDA, M., HIGASHINO, Y., UTSU, N., NAKANO, A., NAKAMURA, S., HASHIMOTO, T., ANDO, K., SAKAMOTO, T., PRINS, F. J., LOK, D., MILHOUS, J. G.-J., VIERGEVER, E., WILLEMS, F., SWART, H., ALINGS, M., BREEDVELD, R., DE VRIES, K.-J., VAN DER BORGH, R., OEI, F., ZOET-NUGTEREN, S., KRAGTEN, H., HERRMAN, J. P., VAN BERGEN, P., GOSSELINK, M., HOEKSTRA, E., ZEGERS, E., RONNER, E., DEN HARTOG, F., BARTELS, G., NIEROP, P., VAN DER ZWAAN, C., VAN ECK, J., VAN GORSELEN, E., GROENEMEIJER, B., HOOGSLAG, P., DE GROOT, M. R., LOYOLA, A., SULIT, D. J., REY, N., ABOLA, M. T., MORALES, D., PALOMARES, E., ABAT, M. E., ROGELIO, G., CHUA, P., DEL PILAR, J. C., ALCARAZ, J. D., EBO, G., TIRADOR, L., CRUZ, J., ANONUEVO, J., PITARGUE, A., JANION, M., GUZIK, T., GAJOS, G., ZABOWKA, M., RYNKIEWICZ, A., BRONCEL, M., SZUBA, A., CZARNECKA, D., MAGA, P., STRAZHESKO, I., VASYUK, Y., SIZOVA, Z., POZDNYAKOV, Y., BARBARASH, O., VOEVODA, M., POPONINA, T., REPIN, A., OSIPOVA, I., EFREMUSHKINA, A., NOVIKOVA, N., AVERKOV, O., ZATEYSHCHIKOV, D., VERTKIN, A., AUSHEVA, A., COMMERFORD, P., SEEDAT, S., VAN ZYL, L., ENGELBRECHT, J., MAKOTOKO, E. M., PRETORIUS, C. E., MOHAMED, Z., HORAK, A., MABIN, T., KLUG, E., BAE, J.-H., KIM, C., KIM, C.-J., KIM, D.-S., KIM, Y. J., JOO, S., HA, J.-W., PARK, C. S., KIM, J. Y., KIM, Y.-K., JARNERT, C., MOOE, T., DELLBORG, M., TORSTENSSON, I., ALBERTSSON, P., JOHANSSON, L., AL-KHALILI, F., ALMROTH, H., ANDERSSON, T., PANTEV, E., TENGMARK, B.-O., LIU, B., RASMANIS, G., WAHLGREN, C.-M., MOCCETTI, T., PARKHOMENKO, A., TSELUYKO, V., VOLKOV, V., KOVAL, O., KONONENKO, L., PROKHOROV, O., VDOVYCHENKO, V., BAZYLEVYCH, A., RUDENKO, L., VIZIR, V., KARPENKO, O., MALYNOVSKY, Y., KOVAL, V., STOROZHUK, B., COTTON, J., VENKATARAMAN, A., MORIARTY, A., CONNOLLY, D., DAVEY, P., SENIOR, R., BIRDI, I., CALVERT, J., DONNELLY, P., TREVELYAN, J., CARTER, J., PEACE, A., AUSTIN, D., KUKREJA, N., HILTON, T., SRIVASTAVA, S., WALSH, R., FIELDS, R., HAKAS, J., PORTNAY, E., GOGIA, H., SALACATA, A., HUNTER, J. J., BACHARACH, J. M., SHAMMAS, N., SURESH, D., SCHNEIDER, R., GURBEL, P., BANERJEE, S., GRENA, P., BEDWELL, N., SLOAN, S., LUPOVITCH, S., SONI, A., GIBSON, K., SANGRIGOLI, R., MEHTA, R., I-HSUAN TSAI, P., GILLESPIE, E., DEMPSEY, S., HAMROFF, G., BLACK, R., LADER, E., KOSTIS, J. B., BITTNER, V., MCGUINN, W., BRANCH, K., MALHOTRA, V., MICHAELSON, S., VACANTE, M., MCCORMICK, M., ARIMIE, R., CAMP, A., DAGHER, G., KOSHY, N. M., THEW, S., COSTELLO, F., HEIMAN, M., CHILTON, R., MORAN, M., ADLER, F., COMEROTA, A., SEIWERT, A., FRENCH, W., SEROTA, H., HARRISON, R., BAKAEEN, F., OMER, S., CHANDRA, L., WHELAN, A., BOYLE, A., ROBERTS-THOMSON, P., ROGERS, J., CARROLL, P., COLQUHOUN, D., SHAW, J., BLOMBERY, P., AMERENA, J., HII, C., ROYSE, A., SINGH, B., SELVANAYAGAM, J., JANSEN, S., LO, W., HAMMETT, C., POULTER, R., NARASIMHAN, S., WIGGERS, H., NIELSEN, H., GISLASON, G., KOBER, L., HOULIND, K., BOENELYKKE SOERENSEN, V., DIXEN, U., REFSGAARD, J., ZEUTHEN, E., SOEGAARD, P., HRANAI, M., GASPAR, L., PELLA, D., HATALOVA, K., DROZDAKOVA, E., COMAN, I., DIMULESCU, D., VINEREANU, D., CINTEZA, M., SINESCU, C., ARSENESCU, C., BENEDEK, I., BOBESCU, E., DOBREANU, D., GAITA, D., IANCU, A., ILIESIU, A., LIGHEZAN, D., PETRESCU, L., PIRVU, O., TEODORESCU, I., TESLOIANU, D., VINTILA, M. M., & CHIONCEL, O.
- Affiliations
- Population Health Research Institute (CA)
- Charles University (CZ)
- Thrombosis Research Institute (GB)
- Semmelweis University (HU)
- Associazione Nazionale Medici Cardiologi Ospedalieri (IT)
- University of Würzburg (DE)
- Fu Wai Hospital (CN)
- Ollscoil na Gaillimhe – University of Galway (IE)
- University of Edinburgh (GB)
- Brigham and Women's Hospital (US)
- Bayer (Germany) (DE)
- Monash University (AU)
- KU Leuven (BE)
- Bayer (United States) (US)
- Universidad Autónoma de Madrid (ES)
- Estudios Clínicos Latinoamérica (AR)
- Hamilton General Hospital (CA)
- McMaster University (CA)
- University of Washington (US)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Centre Hospitalier Universitaire de Montpellier (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Paris Cardiovascular Research Center (FR)
- University of Cape Town (ZA)
- Centre Hospitalier Universitaire de Nîmes (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Werkgroep Cardiologische centra Nederland (NL)
- University of Debrecen (HU)
- University of Trieste (IT)
- Sahlgrenska University Hospital (SE)
- Karolinska Institutet (SE)
- Hôpital Universitaire Dupuytren (FR)
- Istituto Cardiocentro Ticino (CH)
- Danylo Halytsky Lviv National Medical University (UA)
- Foscal Hospital (CO)
- National Research Center for Preventive Medicine (RU)
- Carol Davila University of Medicine and Pharmacy (RO)
- Institutul de Urgenţă pentru Boli Cardiovasculare "Prof.Dr. C.C. Iliescu" (RO)
- Corresponding author
- Anand, Sonia S
- ORCID
- Anand, Sonia S
- Bosch, Jackie
- Eikelboom, John W
- Connolly, Stuart J
- Kakkar, Ajay K
- Keltai, Katalin
- Maggioni, Aldo P
- Störk, Stefan
- Zhu, Jun
- O'Donnell, Martin
- Fox, Keith A A
- Bhatt, Deepak L
- Misselwitz, Frank
- Vanassche, Thomas
- Leong, Darryl P
- Bangdiwala, Shrikant I
- Hart, Robert G
- Yusuf, Salim
- SCHYGIEL, PABLO OMAR
- COSTABEL, JUAN PABLO
- MACIN, STELLA MARIS
- GRINFELD, DIEGO
- VERHAMME, PETER
- DEBONNAIRE, PHILIPPE
- VRANCKX, PASCAL
- ELEGEERT, IVAN
- HOFFER, ETIENNE
- MANENTI, EULER
- REIS, GILMAR
- HERNANDES, MAURO
- TANAJURA, LUIZ FERNANDO
- TYTUS, RICHARD
- LONN, EVA
- LAMY, ANDRE
- NOISEUX, NICOLAS
- BAINEY, KEVIN
- DAGENAIS, GILLES R
- NGUYEN, MICHEL
- GUZMAN, RANDOLPH
- KHAYKIN, YAARIV
- GOSSELIN, GILBERT
- HUYNH, THAO
- ROY, ANNIE
- JIA, KAIYING
- WU, SHULIN
- ZHANG, JIWEI
- GE, JUNBO
- FU, GUOSHENG
- VESGA, BORIS
- LUBANDA, JEAN-CLAUDE
- MOTOVSKA, ZUZANA
- BRANNY, MARIAN
- HOMZA, MIROSLAV
- BRTKO, MIROSLAV
- DUARTE, YAN CARLOS
- SANCHEZ, MAYRA
- TUOMILEHTO, JAAKKO
- KANTOLA, ILKKA
- LECLERCQ, FLORENCE
- BOCCARA, FRANCK
- MESSAS, EMMANUEL
- SEVESTRE, MARIE ANTOINETTE
- CAYLA, GUILLAUME
- MOTREFF, PASCAL
- STELLBRINK, CHRISTOPH
- OPITZ, CHRISTIAN
- NIKOL, SIGRID
- SCHELLONG, SEBASTIAN
- DAVIERWALA, PIROZE
- VORPAHL, MARC
- KORANYI, LASZLO
- MURPHY, ANDREW
- MAHON, NIALL
- HALABI, MAJDI
- ZELTSER, DAVID
- KATZ, AMOS
- ATAR, SHAUL
- FAGGIANO, POMPILIO
- ROBBA, DEBORA
- MOS, LUCIO
- SINAGRA, GIANFRANCO
- GULIZIA, MICHELE MASSIMO
- GALVANI, MARCELLO
- PERNA, GIAN PIERO
- OZAKI, YUKIO
- HIGASHIUE, SHINICHI
- HOSOKAWA, SHINOBU
- FUJII, KENSHI
- KIMURA, KAZUO
- HIGUCHI, YOSHIHARU
- NODA, TOSHIYUKI
- HIRAYAMA, ATSUSHI
- INOKO, MORIAKI
- MANITA, MAMORU
- AKO, JUNYA
- YOSHIDA, TETSURO
- SHIMOMURA, HIDEKI
- KINOSHITA, NORIYUKI
- TAKAHASHI, AKIHIKO
- YUSOFF, KHALID
- KASIM, SAZZLI
- NAKANO, AKIHIKO
- NAKAMURA, SHIGERU
- SAKAMOTO, TOMOHIRO
- RONNER, EELKO
- BARTELS, GERARD
- ABOLA, MARIA TERESA
- ABAT, MARC EVANS
- JANION, MARIANNA
- GUZIK, TOMASZ
- GAJOS, GRZEGORZ
- RYNKIEWICZ, ANDRZEJ
- BRONCEL, MARLENA
- SZUBA, ANDRZEJ
- CZARNECKA, DANUTA
- SIZOVA, ZHANNA
- VOEVODA, MIKHAIL
- REPIN, ALEXEY
- EFREMUSHKINA, ANNA
- ZATEYSHCHIKOV, DMITRY
- BAE, JANG-HO
- HA, JONG-WON
- MOOE, THOMAS
- DELLBORG, MIKAEL
- ALBERTSSON, PER
- WAHLGREN, CARL-MAGNUS
- MOCCETTI, TIZIANO
- PARKHOMENKO, ALEXANDER
- TSELUYKO, VIRA
- KOVAL, OLENA
- BAZYLEVYCH, ANDRIY
- KARPENKO, OLEKSANDR
- MALYNOVSKY, YAROSLAV
- COTTON, JAMES
- CONNOLLY, DEREK
- DAVEY, PATRICK
- SENIOR, ROXY
- PEACE, AARON
- AUSTIN, DAVID
- SRIVASTAVA, SUNNY
- SHAMMAS, NICOLAS
- GURBEL, PAUL
- BANERJEE, SUBHASH
- MEHTA, RAJENDRA
- GILLESPIE, EVE
- HAMROFF, GLENN
- LADER, ELLIS
- KOSTIS, JOHN B.
- BITTNER, VERA
- CHILTON, ROBERT
- COMEROTA, ANTHONY
- BAKAEEN, FAISAL
- AMERENA, JOHN
- ROYSE, ALISTAIR
- SELVANAYAGAM, JOSEPH
- JANSEN, SHIRLEY
- HAMMETT, CHRISTOPHER
- POULTER, ROHAN
- NARASIMHAN, SESHASAYEE
- GISLASON, GUNNAR
- HOULIND, KIM
- DIXEN, ULRIK
- REFSGAARD, JENS
- PELLA, DANIEL
- SINESCU, CRINA
- BENEDEK, IMRE
- BOBESCU, ELENA
- DOBREANU, DAN
- IANCU, ADRIAN
- LIGHEZAN, DANIEL
- PETRESCU, LUCIAN
- TESLOIANU, DAN
- CHIONCEL, OVIDIU
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 391
- Issue
- 10117
- Pages
- 219-229
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W4229536675
- Semantic Scholar
- af705d340539758c05004e20b5429bd9700e2fc2
- Cited by
- 879
- References
- 30
- Citations by year
- 2026: 52 · 2025: 62 · 2024: 74 · 2023: 99 · 2022: 109 · 2021: 139 · 2020: 152 · 2019: 112 · 2018: 74
- FWCI
- 72.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Lancet (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- HAL (submittedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
- Lirias (submittedVersion)
- Scopus (Elsevier) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- rivaroxaban, aspirin, peripheral arterial disease, carotid artery disease, coronary artery disease, major adverse limb events, major amputation, cardiovascular mortality, myocardial infarction, stroke, antiplatelet therapy, direct oral anticoagulants, ankle-brachial index, intermittent claudication, asymptomatic carotid stenosis
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