Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism

Ramón Lecumberri; Ana Alfonso; David Jiménez; Carmen Fernández Capitán; Paolo Prandoni; Philip S. Wells; Gemma Vidal; Giovanni Barillari; Manuel Monreal; and the RIETE Investigators

doi:10.1160/TH13-02-0132

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(04): 834-843
DOI: 10.1160/TH13-02-0132

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism

Ramón Lecumberri

¹Hematology Service, Clínica Universidad de Navarra, Pamplona, Spain

,

Ana Alfonso

¹Hematology Service, Clínica Universidad de Navarra, Pamplona, Spain

,

David Jiménez

²Department of Pneumonology, Hospital Universitario Ramón y Cajal, Madrid, Spain

,

Carmen Fernández Capitán

³Department of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain

,

Paolo Prandoni

⁴Department of Cardiothoracic and Vascular Sciences, University of Padua, Padua, Italy

,

Philip S. Wells

⁵Chief and Chair Department of Medicine, University of Ottawa, Ottawa Hospital, General Campus, Ottawa Ontario, Canada

,

Gemma Vidal

⁶Department of Internal Medicine, Corporació Sanitaria Universitaria Parc Taulí, Sabadell, Barcelona, Spain

,

Giovanni Barillari

⁷Department of Internal Medicine, Center for Hemorrhagic and Thrombotic Disorders, Udine, Italy

,

Manuel Monreal

⁸Department of Internal Medicine, Hospital Universitari Germans Trials i Pujol, Badalona, Barcelona, Spain

,

and the RIETE Investigators

› Author Affiliations

Abstract

Summary

In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a ‘real life’ population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 ± 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% CI, 10.2–14.2) for recurrent VTE, and 19.7% (95% CI, 17.4–22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% CI, 13.6–18.9), compared to 2.0% (95% CI, 0–4.2) beyond this period. The CFR of bleeding was 20.2% (95% CI, 17.5–23.1) during the first three months, compared to 18.2% (95% CI, 14.0–23.2) beyond this period. The CFR of recurrent VTE was higher in patients initially presenting with PE (18.5%; 95% CI, 15.3–22.1) than in those with DVT (6.3%; 95% CI, 4.5–8.6), and in patients with provoked VTE (16.3%; 95% CI, 13.6–19.4) than in those with unprovoked VTE (5.5%; 95% CI, 3.5–8.0). In conclusion, the CFR of recurrent VTE decreased over time during anticoagulation, while the CFR of major bleeding remained stable. The CFR of recurrent VTE was higher in patients initially presenting with PE and in those with provoked VTE.

Keywords

Deep-vein thrombosis - pulmonary embolism - major bleeding - recurrent thromboembolism - case-fatality rate

Full Text

References

References
1 Kearon C, Akl EA, Comerota AJ. et al. Antithrombotic therapy and prevention of thrombosis (9th Edition): American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (Suppl) e419S-e494S.
2 Lagerstedt CI, Olsson CG, Fagher BO. et al. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet 1985; 515-518.
3 Hull R, Delmore T, Genton E. et al. Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis. N Engl J Med 1979; 301: 855-858.
4 Levine MN, Hirsh J, Gent M. et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74: 606-611.
5 Kearon C, Ginsberg JS, Kovacs MJ. et al. Extended Low-Intensity Anticoagulation for Thromboembolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-639.
6 Ridker PM, Goldhaber SZ, Danielson E. et al. PREVENT Investigators. Long-term, low-intensity warfarin therapy for prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348: 1425-1434.
7 Schulman S, Rhedin AS, Lindmarker P. et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N Engl J Med 1995; 332: 1661-1665.
8 Agnelli G, Prandoni P, Santamaria MG. et al. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin optimal Duration Italian Trial Investigators. N Engl J Med 2001; 345: 165-169.
9 Pinede L, Ninet J, Duhaut P. et al. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf vein thrombosis. Circulation 2001; 103: 2453-2460.
10 Agnelli G, Prandoni P, Becattini C. et al. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003; 139: 19-25.
11 Carrier M, Le Gal G, Wells PS. et al. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 2010; 152: 578-589.
12 Laporte S, Mismetti P, Décousus 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: 1711-1716.
13 Monreal M, Falgá C, Valdés M. et al. Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: Findings from the RIETE Registry. J Thromb Haemost 2006; 4: 1950-1956.
14 Nieto JA, Solano R, Ruiz-Ribό MD. et al. Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism. Findings from the RIETE Registry. J Thromb Haemost 2010; 8: 1216-1222.
15 Lecumberri R, Soler S, Del Toro J. et al. Effect of the time of diagnosis on outcome in patients with acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2011; 105: 45-51.
16 Sánchez Muñoz-Torrero JF, Bounameaux H, Pedrajas JM. et al. Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis. J Vasc Surg 2011; 54: 26S-32S.
17 Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism. A Meta-Analysis. Ann Intern Med 2003; 139: 893-900.
18 Douketis JD, Kearon C, Bates S. et al. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. J Am Med Assoc 1998; 279: 458-462.
19 Gόmez-Outes A, Lecumberri R, Lafuente-Guijosa A. et al. Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low-molecular-weight heparins: a meta-analysis. J Thromb Haemost 2004; 2: 1581-1587.
20 Klok FA, Zondag W, van Kralingen KW. et al. Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events. Am J Respir Crit Care Med 2010; 181: 501-506.
21 Lee AY, Levine MN, Baker RI. et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-153.
22 Lecumberri R, Rosario E, Pacho J. et al. Fixed-dose low-molecular-weight heparin, bemiparin, in the long-term treatment of venous thromboembolism in patients with transient risk factors in standard clinical practice: the FLEBUS study. J Thromb Haemost 2006; 4: 2504-2508.
23 EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B. et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
24 EINSTEIN-PE Investigators, Büller HR, Prins MH, Lensin AW. et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366: 1287-1297.
25 Prandoni P, Lensing AW, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100: 3484-3488.
26 Ansell J, Hollowell J, Pengo P. et al. Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the international study of anticoagulation management (ISAM). J Thromb Thrombolysis 2007; 23: 83-91.
27 Menéndez-Jándula B, Souto JC, Oliver A. et al. Comparing self-management of oral anticoagulant therapy with clinic management: a randomized trial. Ann Intern Med 2005; 142: 1-10.
28 Marco F, Sedano C, Bermúdez A. et al. A prospective controlled study of a computer-assisted acenocoumarol dosage program. Pathophysiol Haemost Thromb 2003; 33: 59-63.
29 Andras A, Sala Tenna A, Crawford F. Vitamin K antagonists or low-molecular weight heparin for the long term treatment of symptomatic venous thromboembolism. Cochrane Database System Rev 2012; 10: CD002001.
30 Gallerani M, Manfredini R, Ricci L. et al. Sudden death from pulmonary thromboembolism: chronobiological aspects. Eur Heart J 1992; 13: 661-665.