Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism

Julia C Cambron, Elias S Saba, Robert D McBane, Ana I Casanegra, Hector R Villarraga, Damon E Houghton, Danielle T Vlazny, David Froehling, David Hodge, Lisa G Peterson, Dalene M Bott-Kitslaar, Waldemar E Wysokinski, Julia C Cambron, Elias S Saba, Robert D McBane, Ana I Casanegra, Hector R Villarraga, Damon E Houghton, Danielle T Vlazny, David Froehling, David Hodge, Lisa G Peterson, Dalene M Bott-Kitslaar, Waldemar E Wysokinski

Abstract

Objective: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome.

Methods: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories.

Results: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category.

Conclusion: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes.

Trial registration: clinicaltrials.gov Identifier: NCT03504007.

Keywords: AHA, American Heart Association; CRNMB, clinically relevant nonmajor bleeding; CT, computed tomography; DVT, deep vein thrombosis; HR, hazard ratio; NRVD, no right ventricle dysfunction; PE, pulmonary embolism; PESI, Pulmonary Embolism Severity Index; RV, right ventricle; SSO, subsegmental only; VTE, venous thromboembolism.

© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.

Figures

Figure
Figure
Kaplan-Meier curves are shown for the first event of recurrent venous thromboembolism (A), death event (B), first episode of major bleeding (C), and clinically relevant nonmajor bleeding (D) for massive, submassive, no right ventricle dysfunction (NRVD), and subsegmental only (SSO) pulmonary embolism.

References

    1. Tapson V.F. Acute pulmonary embolism. N Engl J Med. 2008;358(10):1037–1052.
    1. Sista A.K., Kuo W.T., Schiebler M., Madoff D.C. Stratification, imaging, and management of acute massive and submassive pulmonary embolism. Radiology. 2017;284(1):5–24.
    1. Heit J.A., Ashrani A.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(02):390–400.
    1. Jaff M.R., McMurtry M.S., Archer S.L., et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788–1830.
    1. Konstantinides S.V., Meyer G., Becattini C., et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) Eur Heart J. 2020;41(4):543–603.
    1. Le Gal G., Righini M., Parent F., Van Strijen M., Couturaud F. Diagnosis and management of subsegmental pulmonary embolism. J Thromb Haemost. 2006;4(4):724–731.
    1. den Exter P.L., van Es J., Klok F.A., et al. Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. Blood. 2013;122(7):1144–1149.
    1. Donze J., Le Gal G., Fine M.J., et al. Prospective validation of the Pulmonary Embolism Severity Index: a clinical prognostic model for pulmonary embolism. Thromb Haemost. 2008;100(5):943–948.
    1. Jimenez D., Aujesky D., Moores L., et al. Simplification of the Pulmonary Embolism Severity Index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15):1383–1389.
    1. Kearon C., Akl E.A., Ornelas J., et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315–352.
    1. Remy-Jardin M., Pistolesi M., Goodman L.R., et al. Management of suspected acute pulmonary embolism in the era of CT angiography: a statement from the Fleischner Society. Radiology. 2007;245(2):315–329.
    1. Wiener R.S., Schwartz L.M., Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831–837.
    1. Bott-Kitslaar D.M., McBane R.D., Casanegra A.I., et al. Apixaban and rivaroxaban in patients with acute venous thromboembolism. Mayo Clin Proc. 2019;94(7):1242–1252.
    1. Wysokinski W.E., Houghton D.E., Casanegra A.I., et al. Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism. Am J Hematol. 2019;94(11):1185–1192.
    1. Khorana A.A., Noble S., Lee A.Y.Y., et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost. 2018;16(9):1891–1894.
    1. Girard P., Penaloza A., Parent F., et al. Reproducibility of clinical events adjudications in a trial of venous thromboembolism prevention. J Thromb Haemost. 2017;15(4):662–669.
    1. Schulman S., Kearon C., Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692–694.
    1. Becattini C., Agnelli G., Vedovati M.C., et al. Multidetector computed tomography for acute pulmonary embolism: diagnosis and risk stratification in a single test. Eur Heart J. 2011;32(13):1657–1663.
    1. Trujillo-Santos J., den Exter P.L., Gomez V., et al. Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and meta-analysis. J Thromb Haemost. 2013;11(10):1823–1832.
    1. Becattini C., Agnelli G., Germini F., Vedovati M.C. Computed tomography to assess risk of death in acute pulmonary embolism: a meta-analysis. Eur Respir J. 2014;43(6):1678–1690.
    1. Sanchez O., Trinquart L., Colombet I., et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur Heart J. 2008;29(12):1569–1577.
    1. Coutance G., Cauderlier E., Ehtisham J., Hamon M., Hamon M. The prognostic valueof markers of right ventricular dysfunction in pulmonary embolism: a meta-analysis. Crit Care. 2011;15(2):R103.
    1. Büller H.R., Prins M.H., Lensin A.W., et al. EINSTEIN–PE Investigators Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287–1297.
    1. Goldhaber S.Z., Visani L., De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) Lancet. 1999;353(9162):1386–1389.
    1. Laporte S., Mismetti P., Decousus H., et al. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation. 2008;117(13):1711–1716.
    1. Jimenez D., Aujesky D., Diaz G., et al. Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med. 2010;181(9):983–991.
    1. Beyer-Westendorf J. What have we learned from real-world NOAC studies in venous thromboembolism treatment? Thromb Res. 2018;163:83–91.
    1. D'Agostino C., Zonzin P., Enea I., et al. ANMCO position paper: long-term follow-up of patients with pulmonary thromboembolism. Eur Heart J Suppl. 2017;19(suppl D):D309–D332.
    1. Heit J.A., Spencer F.A., White R.H. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14.
    1. Kasper W., Konstantinides S., Geibel A., et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol. 1997;30(5):1165–1171.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere