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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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“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]
In the citing paper
“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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Peripheral arterial disease and the cardiometabolic syndrome: assessment and management
Heiß, C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99991-5.00015-2
Acute arterial thrombosis in anticoagulated patient for acute pulmonary thromboembolism
Chelikikj, A., Poposka, L., Nastevska, E. G., Kandic, E., Bushljetikj, O., & ZİMBAKOV, Z. (2023) · Turkish Journal of Internal Medicine · doi:10.46310/tjim.1176071
Managing Stable Coronary Artery Disease in Diabetes
Koulouridis, I., & Johnstone, M. T. (2023) · Contemporary cardiology · doi:10.1007/978-3-031-13177-6_23
Lesiones oclusivas ateromatosas crónicas de la aorta y de los miembros inferiores
Koskas, F., Couture, T., Koskas, L., & Davaine, J. (2023) · EMC - Tratado de Medicina · doi:10.1016/s1636-5410(23)47955-x
Dietary intake and vascular disease: you are what you eat
Wan, D., & Anand, S. S. (2023) · University of Toronto Medical Journal · doi:10.33137/utmj.v100i2.41466
Self-citationPeripheral Arterial Disease and the Pharmacist’s Role in Management
Stacy, Z. A. (2023) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1155/2023/2352051
“Major amputations were reduced by 70% in patients with PAD receiving rivaroxaban plus aspirin versus aspirin alone (0.2% vs. 0.7%; HR, 0.30; 95% CI, 0.11–0.80) [49].”
InfluentialLesioni occlusive ateromatose croniche dell’aorta e degli arti inferiori
Koskas, F., Couture, T., Koskas, L., & Davaine, J. (2023) · EMC - AKOS - Trattato di Medicina · doi:10.1016/s1634-7358(23)47940-5
Patologia aterosclerotica delle arterie a distribuzione cerebrale
Isabel, C., Seners, P., Calvet, D., & Mas, J. (2019) · EMC - Neurologia · doi:10.1016/s1634-7072(19)43054-7
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Siegbahn, A., Svensson, P. J., Wallén, H., & Wallentin, L. C. (2023) · Oxford University Press eBooks · doi:10.1093/med/9780192869227.003.0011
Shah, A., Dabbous, F., Shah, S., Ashton, V., & Kharat, A. A. (2023) · Journal of Medical Economics · doi:10.1080/13696998.2023.2290386
“The HRs of treatment effect used in this analysis were derived on the intention-to-treat basis in all randomized patients, regardless of whether they received the treatment assigned to them in the COMPASS and the VOYAGER-PAD trials 12,14 .”
InfluentialVoyaging to Safety: Anticoagulation in Peripheral Artery Disease and Limb Revascularisation
Shahid, M., Franco, N. F., & Sistla, L. (2024) · IntechOpen eBooks · doi:10.5772/intechopen.112773
Balletshofer, B. M., Böckler, D., Diener, H., Heckenkamp, J., Ito, W. D., Katoh, M., Lawall, H., Malyar, N. M., Qiu, H. J., Reimer, P., et al. (2024) · Die Diabetologie · doi:10.1007/s11428-023-01141-1
“Bei Patienten mit pAVK kommt es bei einem RR< 120mmHg und >160mmHg zu mehr Beinereignissen [14].”
Manejo integral de los factores de riesgo en enfermedad arterial periférica
Cuixart, C. B., González, P. B., Pelaez, I. M., & Ruiz, D. S. (2024) · FMC - Formación Médica Continuada en Atención Primaria · doi:10.1016/j.fmc.2023.07.003
Asymptomatische periphere arterielle Verschlusskrankheit (pAVK)
Stella, J. (2024) · Springer Reference Medizin · doi:10.1007/978-3-662-61379-5_67-1
Wille, H. (2023) · Springer eBooks · doi:10.1007/978-3-662-68371-2_9
Barros, P. L., de Castro, D. J. M. B., Goldman, R. E., & Kwong, M. (2024) · Journal of Vascular Surgery Venous and Lymphatic Disorders · doi:10.1016/j.jvsv.2024.101858
“25 Although most patients with incidental DVTs in this study did well, one patient did have signi fi cant bleeding complications from anticoagulation, suggesting that there is a cost to these incidental diagnoses.”
BackgroundThe paradox of direct-acting anticoagulants in peripheral arterial disease in Spain
Esteban, C. (2024) · Angiología · doi:10.20960/angiologia.00638
Arakelyan, V. S., Erlikh, A. D., Amirov, N. S., Dubar, E., Vogtländer, K., & Debus, S. E. (2024) · Rational Pharmacotherapy in Cardiology · doi:10.20996/1819-6446-2024-3038
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Müller, K. (2024) · Kardiologie up2date · doi:10.1055/a-2198-0676
Antiplatelet Treatment With Dual Pathway Inhibition: A Pathway of Consistency?
Geisler, T. (2024) · European Cardiology Review · doi:10.15420/ecr.2023.52
“4,8,9 The mortality effect may be partly caused by a larger benefit in patients with heart failure in the COMPASS trial, an effect that could not be reproduced in a larger randomised trial focusing on patients with recent worsening heart failure and CAD with high use of guideline-based…”
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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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