Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry

Registro Informatizado de Enfermedad Tromboembólica Investigators

doi:10.1016/j.jvsv.2019.03.011

Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry

Registro Informatizado de Enfermedad Tromboembólica Investigators

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Objective: Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE. Methods: We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ² test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of <.05 was considered statistically significant. Results: We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE. Conclusions: Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

Original language	English
Pages (from-to)	353-359.e1
Journal	Journal of Vascular Surgery: Venous and Lymphatic Disorders
Volume	8
Issue number	3
DOIs	https://doi.org/10.1016/j.jvsv.2019.03.011
State	Published - May 2020

Bibliographical note

Publisher Copyright:
© 2019 Society for Vascular Surgery

Funding

We express our gratitude to Sanofi Spain for supporting the RIETE Registry with an unrestricted educational grant. We also express our gratitude to Bayer Pharma AG for supporting the RIETE Registry. Bayer Pharma AG's support was limited to the part of RIETE outside of Spain, which accounts for 25.10% of the total patients included in the RIETE Registry. We also thank the RIETE Registry Coordinating Center, S&H Medical Science Service, for their quality control data and logistic and administrative support. Conception and design: IG, AT, MM Analysis and interpretation: IG, AT, MM Data collection: IG, LC, OI, BenB, AT, BehB, CF, JP, RO, RQ, MM Writing the article: IG, AT, MM Critical revision of the article: IG, LC, OI, BenB, AT, BehB, CF, JP, RO, RQ, MM Final approval of the article: IG, LC, OI, BenB, AT, BehB, CF, JP, RO, RQ, MM Statistical analysis: Not applicable Obtained funding: Not applicable Overall responsibility: IG IG and AT contributed equally to this article and share co-first authorship. We express our gratitude to Sanofi Spain for supporting the RIETE Registry with an unrestricted educational grant. We also express our gratitude to Bayer Pharma AG for supporting the RIETE Registry. Bayer Pharma AG's support was limited to the part of RIETE outside of Spain, which accounts for 25.10% of the total patients included in the RIETE Registry. We also thank the RIETE Registry Coordinating Center, S&H Medical Science Service, for their quality control data and logistic and administrative support. Appendix (online only) Coordinator of the RIETE Registry: Dr Manuel Monreal (Spain); RIETE Steering Committee Members: Dr Paolo Prandoni (Italy), Dr Benjamin Brenner (Israel), and Dr Dominique Farge-Bancel (France); RIETE National Coordinators: Dr Raquel Barba (Spain), Dr Pierpaolo Di Micco (Italy), Dr Laurent Bertoletti (France), Dr Inna Tzoran (Israel), Dr Abilio Reis (Portugal), Dr Henri Bounameaux (Switzerland), Dr Radovan Malý (Czech Republic), Dr Peter Verhamme (Belgium), Dr Marijan Bosevski (Republic of Macedonia), Dr Joseph A. Caprini (United States), Dr Hanh My Bui (Vietnam); RIETE Registry Coordinating Center: S&H Medical Science Service; Members of the RIETE Group: Spain—Adarraga MD, Aibar MA, Aibar J, Amado C, Arcelus JI, Azcarate PM, Ballaz A, Barba R, Barrón M, Barrón-Andrés B, Bascuñana J, Blanco-Molina A, Camon AM, Carrasco C, Castro J, de Ancos C, del Toro J, Demelo P, Díaz-Pedroche MC, Díaz-Peromingo JA, Díaz-Simón R, Encabo M, Falgá C, Farfán AI, Fernández-Capitán C, Fernández-Criado MC, Fidalgo MA, Font C, Font L, García MA, García-Bragado F, García-Morillo M, García-Raso A, Gavín O, Gaya I, Gayol MC, Gil-Díaz A, Guirado L, Gómez V, González-Martínez J, Grau E, Gutiérrez J, Hernández Blasco LM, Iglesias M, Jara-Palomares L, Jaras MJ, Jiménez D, Jou I, Joya MD, Lalueza A, Lima J, Llamas P, Lobo JL, López-Jiménez L, López-Miguel P, López-Nuñez JJ, López-Reyes R, López-Sáez JB, Lorente MA, Lorenzo A, Loring M, Lumbierres M, Madridano O, Maestre A, Marchena PJ, Martín-Guerra JM, Martín Fernández M, Mellado M, Monreal M, Morales MV, Nieto JA, Núñez MJ, Olivares MC, Otalora S, Otero R, Pedrajas JM, Pellejero G, Pérez-Pinar M, Pérez-Rus G, Peris ML, Pesce ML, Porras JA, Rivas A, Rodríguez-Dávila MA, Rodríguez-Fernández L, Rodríguez-Hernández A, Rodríguez-Martín C, Rubio CM, Ruiz-Alcaraz S, Ruiz-Artacho P, Ruiz-Ruiz J, Ruiz-Sada P, Sahuquillo JC, Salazar V, Sampériz A, Sánchez-Muñoz-Torrero JF, Sancho T, Sanoja I, Soler S, Soto MJ, Suriñach JM, Tolosa C, Torres MI, Trujillo-Santos J, Uresandi F, Usandizaga E, Valle R, and Vidal G; Argentina—Gutiérrez P, Vázquez FJ, and Vilaseca A; Belgium—Vanassche T, Vandenbriele C, and Verhamme P; Czech Republic—Hirmerova J and Malý R; Ecuador—Salgado E; France—Benzidia I, Bertoletti L, Bura-Riviere A, Debourdeau P, Falvo N, Farge-Bancel D, Hij A, Mahé I, and Moustafa F; Israel: Braester A, Brenner B, Ellis M, and Tzoran I; Italy—Barillari G, Bilora F, Bortoluzzi C, Brandolin B, Bucherini E, Ciammaichella M, Dentali F, Di Micco P, Grandone E, Imbalzano E, Lessiani G, Maida R, Mastroiacovo D, Mumoli N, Vo Hong N, Pace F, Parisi R, Pesavento R, Pinelli M, Prandoni P, Quintavalla R, Rocci A, Siniscalchi C, Tufano A, and Visonà A; Latvia—Skride A, Sablinskis K, and Sablinskis M; Republic of Macedonia—Bosevski M and Zdraveska M; Switzerland—Bounameaux H, Fresa M, Ney B, and Mazzolai L; United States—Caprini J, and Tafur A; Vietnam—Bui HM. Appendix Additional material for this article may be found online at www.jvsvenous.org .

Funders	Funder number
Rubio
S&H Medical Science Service	AI
National Heart, Lung, and Blood Institute	T32HL007854
Bayer

Keywords

Major adverse cardiovascular events
Major adverse limb events
Provoked
VTE
Venous thromboembolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jvsv.2019.03.011

Cite this

Registro Informatizado de Enfermedad Tromboembólica Investigators (2020). Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry. Journal of Vascular Surgery: Venous and Lymphatic Disorders, 8(3), 353-359.e1. https://doi.org/10.1016/j.jvsv.2019.03.011

Registro Informatizado de Enfermedad Tromboembólica Investigators. / Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism : Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry. In: Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2020 ; Vol. 8, No. 3. pp. 353-359.e1.

@article{1aa494175dd74020b3aaf2b442795e22,

title = "Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboemb{\'o}lica Registry",

abstract = "Objective: Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE. Methods: We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboemb{\'o}lica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of <.05 was considered statistically significant. Results: We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE. Conclusions: Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.",

keywords = "Major adverse cardiovascular events, Major adverse limb events, Provoked, VTE, Venous thromboembolism",

author = "{Registro Informatizado de Enfermedad Tromboemb{\'o}lica Investigators} and Iva Golemi and Lauren Cote and Omer Iftikhar and Benjamin Brenner and Alfonso Tafur and Behnood Bikdeli and Carmen Fern{\'a}ndez-Capit{\'a}n and Pedrajas, {Jos{\'e} Mar{\'i}a} and Remedios Otero and Roberto Quintavalla and Manuel Monreal and Paolo Prandoni and Dominique Farge-Bancel and Raquel Barba and {Di Micco}, Pierpaolo and Laurent Bertoletti and Inna Tzoran and Abilio Reis and Henri Bounameaux and Radovan Mal{\'y} and Peter Verhamme and Marijan Bosevski and Caprini, {Joseph A.} and Bui, {Hanh My} and Adarraga, {M. D.} and Aibar, {M. A.} and J. Aibar and C. Amado and Arcelus, {J. I.} and Azcarate, {P. M.} and A. Ballaz and R. Barba and M. Barr{\'o}n and B. Barr{\'o}n-Andr{\'e}s and J. Bascu{\~n}ana and A. Blanco-Molina and Camon, {A. M.} and C. Carrasco and J. Castro and {de Ancos}, C. and {del Toro}, J. and P. Demelo and D{\'i}az-Pedroche, {M. C.} and D{\'i}az-Peromingo, {J. A.} and R. D{\'i}az-Sim{\'o}n and M. Encabo and C. Falg{\'a} and Farf{\'a}n, {A. I.} and C. Fern{\'a}ndez-Capit{\'a}n and A. Braester",

note = "Publisher Copyright: {\textcopyright} 2019 Society for Vascular Surgery",

year = "2020",

month = may,

doi = "10.1016/j.jvsv.2019.03.011",

language = "אנגלית",

volume = "8",

pages = "353--359.e1",

journal = "Journal of Vascular Surgery: Venous and Lymphatic Disorders",

issn = "2213-333X",

publisher = "Elsevier Inc.",

number = "3",

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Registro Informatizado de Enfermedad Tromboembólica Investigators 2020, 'Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry', Journal of Vascular Surgery: Venous and Lymphatic Disorders, vol. 8, no. 3, pp. 353-359.e1. https://doi.org/10.1016/j.jvsv.2019.03.011

Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry. / Registro Informatizado de Enfermedad Tromboembólica Investigators.
In: Journal of Vascular Surgery: Venous and Lymphatic Disorders, Vol. 8, No. 3, 05.2020, p. 353-359.e1.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism

T2 - Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry

AU - Registro Informatizado de Enfermedad Tromboembólica Investigators

AU - Golemi, Iva

AU - Cote, Lauren

AU - Iftikhar, Omer

AU - Brenner, Benjamin

AU - Tafur, Alfonso

AU - Bikdeli, Behnood

AU - Fernández-Capitán, Carmen

AU - Pedrajas, José María

AU - Otero, Remedios

AU - Quintavalla, Roberto

AU - Monreal, Manuel

AU - Prandoni, Paolo

AU - Farge-Bancel, Dominique

AU - Barba, Raquel

AU - Di Micco, Pierpaolo

AU - Bertoletti, Laurent

AU - Tzoran, Inna

AU - Reis, Abilio

AU - Bounameaux, Henri

AU - Malý, Radovan

AU - Verhamme, Peter

AU - Bosevski, Marijan

AU - Caprini, Joseph A.

AU - Bui, Hanh My

AU - Adarraga, M. D.

AU - Aibar, M. A.

AU - Aibar, J.

AU - Amado, C.

AU - Arcelus, J. I.

AU - Azcarate, P. M.

AU - Ballaz, A.

AU - Barba, R.

AU - Barrón, M.

AU - Barrón-Andrés, B.

AU - Bascuñana, J.

AU - Blanco-Molina, A.

AU - Camon, A. M.

AU - Carrasco, C.

AU - Castro, J.

AU - de Ancos, C.

AU - del Toro, J.

AU - Demelo, P.

AU - Díaz-Pedroche, M. C.

AU - Díaz-Peromingo, J. A.

AU - Díaz-Simón, R.

AU - Encabo, M.

AU - Falgá, C.

AU - Farfán, A. I.

AU - Fernández-Capitán, C.

AU - Braester, A.

PY - 2020/5

Y1 - 2020/5

N2 - Objective: Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE. Methods: We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of <.05 was considered statistically significant. Results: We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE. Conclusions: Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

AB - Objective: Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE. Methods: We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of <.05 was considered statistically significant. Results: We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE. Conclusions: Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

KW - Major adverse cardiovascular events

KW - Major adverse limb events

KW - Provoked

KW - VTE

KW - Venous thromboembolism

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Registro Informatizado de Enfermedad Tromboembólica Investigators. Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2020 May;8(3):353-359.e1. doi: 10.1016/j.jvsv.2019.03.011

Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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