Advertisement

Sex-specific differences in the presentation, clinical course, and quality of life of patients with acute venous thromboembolism according to baseline risk factors. Insights from the PREFER in VTE

Published:March 30, 2021DOI:https://doi.org/10.1016/j.ejim.2021.03.014

      Highlights

      • Women and men have different prevalence of risk factors for venous thromboembolism.
      • Understanding these differences may help to predict sex-related risk of recurrence.
      • Women and men had similar rates of one year recurrent venous thromboembolism (VTE).
      • Women had lower quality of life and treatment satisfaction after the first VTE.

      Abstract

      Introduction

      Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors.

      Methods

      PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes.

      Results

      Of 3,455 patients with acute VTE, 1,623 (47%) were women. The mean age at the time of VTE was 61 (SD 18) in women, 60 (SD 15) in men. The distribution of provoking risk factors was similar between sexes, despite a tendency for higher frequency of minor and major transient risk factors in women, and cancer or unprovoked VTE in men. At 12-month follow-up, VTE recurrence was reported in 74 (6.5%) women and 80 (6.4%) men (absolute risk difference -0.1%, 95% CI -1.9%; +2.1%). In patients with unprovoked VTE, the VTE recurrence rate was 38/612 (6.2%) in women and 53/798 (6.6%) in men (absolute risk difference -0.4, 95% CI -3.0; +2.1%). Multivariable Cox regressions confirmed the absence of sex differences. Quality of life and treatment satisfaction scores one year after VTE were lower in women than in men irrespective of the provoking risk factors (p<0.001 for both scores).

      Conclusions

      Despite differences in the provoking risk factors for VTE, women and men had a similar rate VTE recurrence at one year. After acute VTE, women had lower quality of life and treatment satisfaction scores.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Heit J.A.
        • Lahr B.D.
        • Ashrani A.A.
        • Petterson T.M.
        • Bailey K.R.
        Predictors of venous thromboembolism recurrence, adjusted for treatments and interim exposures: a population-based case-cohort study.
        Thromb Res. 2015; 136: 298-307
        • Roach R.E.
        • Lijfering W.M.
        • Rosendaal F.R.
        • Cannegieter S.C.
        • le Cessie S.
        Sex difference in risk of second but not of first venous thrombosis: paradox explained.
        Circulation. 2014; 129: 51-56
        • Linnemann B.
        • Weingarz L.
        • Schindewolf M.
        • Schwonberg J.
        • Weber A.
        • Herrmann E.
        • et al.
        Prevalence of established risk factors for venous thromboembolism according to age.
        J. Vasc. Surg. Venous. Lymphat. Disord. 2014; 2: 131-139
        • Scheres L.J.J.
        • Brekelmans M.P.A.
        • Beenen L.F.M.
        • Büller H.R.
        • Cannegieter S.C.
        • Middeldorp S.
        Sex-specific differences in the presenting location of a first venous thromboembolism.
        J. Thromb Haemost. 2017; 15: 1344-1350
        • Áinle F.N.
        • Kevane B.
        Which patients are at high risk of recurrent venous thromboembolism (deep vein thrombosis and pulmonary embolism)?.
        Blood Adv. 2020; 4: 5595-5606
        • Douketis J.
        • Tosetto A.
        • Marcucci M.
        • Baglin T.
        • Cosmi B.
        • Cushman M.
        • et al.
        Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis.
        Bmj. 2011; 342: d813
        • Barco S.
        • Klok F.A.
        • Mahé I.
        • Marchena P.J.
        • Ballaz A.
        • Rubio C.M.
        • et al.
        Impact of sex, age, and risk factors for venous thromboembolism on the initial presentation of first isolated symptomatic acute deep vein thrombosis.
        Thromb Res. 2019; 173: 166-171
        • Canonico M.
        • Plu-Bureau G.
        • Lowe G.D.
        • Scarabin P.Y.
        Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis.
        Bmj. 2008; 336: 1227-1231
        • van Langevelde K.
        • Flinterman L.E.
        • van Hylckama Vlieg A.
        • Rosendaal F.R.
        • Cannegieter S.C.
        Broadening the factor V Leiden paradox: pulmonary embolism and deep-vein thrombosis as 2 sides of the spectrum.
        Blood. 2012; 120: 933-946
        • Hvas A.M.
        • Favaloro E.J.
        Gender related issues in thrombosis and hemostasis.
        Expert Rev. Hematol. 2017; 10: 941-949
        • Münster A.M.
        • Rasmussen T.B.
        • Falstie-Jensen A.M.
        • Harboe L.
        • Stynes G.
        • Dybro L.
        • et al.
        A changing landscape: temporal trends in incidence and characteristics of patients hospitalized with venous thromboembolism 2006-2015.
        Thromb Res. 2019; 176: 46-53
        • Klil-Drori A.J.
        • Coulombe J.
        • Suissa S.
        • Hirsch A.
        • Tagalakis V.
        Temporal trends in outpatient management of incident pulmonary embolism and associated mortality.
        Thromb Res. 2018; 161: 111-116
        • Heit J.A.
        • Ashrani A.
        • Crusan D.J.
        • McBane R.D.
        • Petterson T.M.
        • Bailey K.R.
        Reasons for the persistent incidence of venous thromboembolism.
        Thromb Haemost. 2017; 117: 390-400
        • Trinchero A.
        • Scheres L.J.J.
        • Prochaska J.H.
        • Ambaglio C.
        • Wild P.S.
        • Middeldorp S.
        • et al.
        Sex-specific differences in the distal versus proximal presenting location of acute deep vein thrombosis.
        Thromb Res. 2018; 172: 74-79
        • Barco S.
        • Mahmoudpour S.H.
        • Valerio L.
        • Klok F.A.
        • Münzel T.
        • Middeldorp S.
        • et al.
        Trends in mortality related to pulmonary embolism in the European region, 2000-15: analysis of vital registration data from the WHO mortality database.
        Lancet Respir. Med. 2020; 8: 277-287
        • Barco S.
        • Valerio L.
        • Ageno W.
        • Cohen A.T.
        • Goldhaber S.Z.
        • Hunt B.J.
        • et al.
        Age-sex specific pulmonary embolism-related mortality in the USA and Canada, 2000-18: an analysis of the WHO mortality database and of the CDC multiple cause of death database.
        Lancet Respir. Med. 2020;
        • de Moreuil C.
        • Le Mao R.
        • Le Moigne E.
        • Pan-Petesch B.
        • Tromeur C.
        • Hoffmann C.
        • et al.
        Long-term recurrence risk after a first venous thromboembolism in men and women under 50 years old: a French prospective cohort.
        Eur. J. Intern. Med. 2020;
        • Yoshikawa Y.
        • Yamashita Y.
        • Morimoto T.
        • Amano H.
        • Takase T.
        • Hiramori S.
        • et al.
        Sex differences in clinical characteristics and outcomes of patients with venous thromboembolism- from the command vte registry.
        Circ. J.: off. J. Japanese Circ. Soc. 2019; 83: 1581-1589
        • Barrios D.
        • Morillo R.
        • Guerassimova I.
        • Barbero E.
        • Escobar-Morreale H.
        • Cohen A.T.
        • et al.
        Sex differences in the characteristics and short-term prognosis of patients presenting with acute symptomatic pulmonary embolism.
        PLoS ONE. 2017; 12e0187648
        • Alotaibi G.S.
        • Almodaimegh H.
        • McMurtry M.S.
        • Wu C.
        Do women bleed more than men when prescribed novel oral anticoagulants for venous thromboembolism? A sex-based meta-analysis.
        Thromb Res. 2013; 132: 185-189
        • Loffredo L.
        • Violi F.
        • Perri L
        Sex related differences in patients with acute venous thromboembolism treated with new oral anticoagulants. A meta-analysis of the interventional trials.
        Int. J. Cardiol. 2016; 212: 255-258
        • Klok F.A.
        • van Kralingen K.W.
        • van Dijk A.P.
        • Heyning F.H.
        • Vliegen H.W.
        • Kaptein A.A.
        • et al.
        Quality of life in long-term survivors of acute pulmonary embolism.
        Chest. 2010; 138: 1432-1440
        • Lubberts B.
        • Paulino Pereira N.R.
        • Kabrhel C.
        • Kuter D.J.
        • DiGiovanni C.W
        What is the effect of venous thromboembolism and related complications on patient reported health-related quality of life? A meta-analysis.
        Thromb Haemost. 2016; 116: 417-431
        • Tavoly M.
        • Utne K.K.
        • Jelsness-Jorgensen L.P.
        • Wik H.S.
        • Klok F.A.
        • Sandset P.M.
        • et al.
        Health-related quality of life after pulmonary embolism: a cross-sectional study.
        BMJ Open. 2016; 6e013086
        • Keita I.
        • Aubin-Auger I.
        • Lalanne C.
        • Aubert J.P.
        • Chassany O.
        • Duracinsky M.
        • et al.
        Assessment of quality of life, satisfaction with anticoagulation therapy, and adherence to treatment in patients receiving long-course vitamin K antagonists or direct oral anticoagulants for venous thromboembolism.
        Patient Prefer. Adherence. 2017; 11: 1625-1634
        • Kearon C.
        • Ageno W.
        • Cannegieter S.C.
        • Cosmi B.
        • Geersing G.J.
        • Kyrle P.A.
        Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH.
        J. Thromb Haemost. 2016; 14: 1480-1483
        • Cushman M.
        • Glynn R.J.
        • Goldhaber S.Z.
        • Moll S.
        • Bauer K.A.
        • Deitcher S.
        • et al.
        Hormonal factors and risk of recurrent venous thrombosis: the prevention of recurrent venous thromboembolism trial.
        J. Thromb Haemost. 2006; 4: 2199-2203
        • Agnelli G.
        • Gitt A.K.
        • Bauersachs R.
        • Fronk E.M.
        • Laeis P.
        • Mismetti P.
        • et al.
        The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE registry.
        Thromb J. 2015; 13: 41
        • Cohen A.T.
        • Gitt A.K.
        • Bauersachs R.
        • Fronk E.M.
        • Laeis P.
        • Mismetti P.
        • et al.
        The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE registry.
        Thromb Haemost. 2017; 117: 1326-1337
        • Prins M.H.
        • Lensing A.W.A.
        • Prandoni P.
        • Wells P.S.
        • Verhamme P.
        • Beyer-Westendorf J.
        • et al.
        Risk of recurrent venous thromboembolism according to baseline risk factor profiles.
        Blood Adv. 2018; 2: 788-796
        • Schulman S.
        • Kearon C.
        Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.
        J. Thromb Haemost. 2005; 3: 692-694
      1. EuroQol Research Foundation. EQ-5D-5 L User guide, 2019. Available from: https://euroqol.org/publications/user-guides.

        • Prins M.H.
        • Guillemin I.
        • Gilet H.
        • Gabriel S.
        • Essers B.
        • Raskob G.
        • et al.
        Scoring and psychometric validation of the perception of anticoagulant treatment questionnaire (PACT-Q).
        Health Qual. Life Outcomes. 2009; 7 (-): 30
        • Enders C.K.
        Applied Missing Data Analysis.
        The Guildford Press, New York2010
        • Marshall A.L.
        • Bartley A.C.
        • Ashrani A.A.
        • Pruthi R.K.
        • Durani U.
        • Gonsalves W.I.
        • et al.
        Sex-based disparities in venous thromboembolism outcomes: a national inpatient sample (NIS)-based analysis.
        Vascu. med. 2017; 22: 121-127
        • Tagalakis V.
        • Kondal D.
        • Ji Y.
        • Boivin J.F.
        • Moride Y.
        • Ciampi A.
        • et al.
        Men had a higher risk of recurrent venous thromboembolism than women: a large population study.
        Gend Med. 2012; 9: 33-43
        • Agnelli G.
        • Becattini C.
        • Prandoni P.
        Recurrent venous thromboembolism in men and women.
        The New Eng. J. Med. 2004; 351 (author reply -8): 2015-2018
        • Lijfering W.M.
        • Veeger N.J.
        • Middeldorp S.
        • Hamulyák K.
        • Prins M.H.
        • Büller H.R.
        • et al.
        A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families.
        Blood. 2009; 114: 2031-2036
        • Prandoni P.
        • Noventa F.
        • Ghirarduzzi A.
        • Pengo V.
        • Bernardi E.
        • Pesavento R.
        • et al.
        The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients.
        Haematologica. 2007; 92: 199-205
        • Olié V.
        • Zhu T.
        • Martinez I.
        • Scarabin P.Y.
        • Emmerich J.
        Sex-specific risk factors for recurrent venous thromboembolism.
        Thromb Res. 2012; 130: 16-20
        • Blanco-Molina A.
        • Enea I.
        • Gadelha T.
        • Tufano A.
        • Bura-Riviere A.
        • Di Micco P.
        • et al.
        Sex differences in patients receiving anticoagulant therapy for venous thromboembolism.
        Med. (Baltimore). 2014; 93: 309-317
        • Albertsen I.E.
        • Nielsen P.B.
        • Søgaard M.
        • Goldhaber S.Z.
        • Overvad T.F.
        • Rasmussen L.H.
        • et al.
        Risk of recurrent venous thromboembolism: a danish nationwide cohort study.
        Am. J. Med. 2018; 131 (e4): 1067-1074
        • Martín-Martos F.
        • Trujillo-Santos J.
        • Barrón M.
        • Vela J.
        • Javier Marchena P.
        • Braester A.
        • et al.
        Gender differences in cancer patients with acute venous thromboembolism.
        Thromb Res. 2015; 135: S12-S15
        • Keller K.
        • Tesche C.
        • Gerhold-Ay A.
        • Nickels S.
        • Klok F.A.
        • Rappold L.
        • et al.
        Quality of life and functional limitations after pulmonary embolism and its prognostic relevance.
        J. Thromb Haemost. 2019; 17: 1923-1934
        • Koh Y.
        • Stehli J.
        • Martin C.
        • Brennan A.
        • Dinh D.T.
        • Lefkovits J.
        • et al.
        Does sex predict quality of life after acute coronary syndromes: an Australian, state-wide, multicentre prospective cohort study.
        BMJ Open. 2019; 9e034034
        • Munyombwe T.
        • Hall M.
        • Dondo T.B.
        • Alabas O.A.
        • Gerard O.
        • West R.M.
        • et al.
        Quality of life trajectories in survivors of acute myocardial infarction: a national longitudinal study.
        Heart. 2020; 106: 33-39
        • Calvert M.
        • Kyte D.
        • Mercieca-Bebber R.
        • Slade A.
        • Chan A.W.
        • King M.T.
        • et al.
        Guidelines for inclusion of patient-reported outcomes in clinical trial protocols: the spirit-pro extension.
        JAMA. 2018; 319: 483-494
        • Porter M.E.
        What is value in health care?.
        The New England journal of medicine. 2010; 363: 2477-2481
        • Valerio L.
        • Barco S.
        • Jankowski M.
        • Rosenkranz S.
        • Lankeit M.
        • Held M.
        • et al.
        Quality of life three and twelve months after acute pulmonary embolism: analysis from a prospective multicenter cohort study.
        Chest. 2021;
        • Andrade L.F.
        • Saba G.
        • Ricard J.D.
        • Messika J.
        • Gaillat J.
        • Bonnin P.
        • et al.
        Health related quality of life in patients with community-acquired pneumococcal pneumonia in France.
        Health Qual Life Outcomes. 2018; 16: 28
        • Chuang L.H.
        • Gumbs P.
        • van Hout B.
        • Agnelli G.
        • Kroep S.
        • Monreal M.
        • et al.
        Health-related quality of life and mortality in patients with pulmonary embolism: a prospective cohort study in seven European countries.
        Qual. Life Res. 2019; 28: 2111-2124