Death due to recurrent thromboembolism among younger healthier individuals hospitalized for idiopathic pulmonary embolism

Richard H. White; Hong Zhou; Susan Murin

doi:10.1160/TH07-09-0557

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(04): 683-690
DOI: 10.1160/TH07-09-0557

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Death due to recurrent thromboembolism among younger healthier individuals hospitalized for idiopathic pulmonary embolism

Authors

Richard H. White

¹Division of General Medicine, University of California, Davis, California, USA
Hong Zhou

¹Division of General Medicine, University of California, Davis, California, USA
Susan Murin

²Division of Pulmonary and Critical Care Medicine, University of California, Davis, California, USA

Abstract

Summary

The incidence of death due to recurrent pulmonary embolism (PE) after a first-time idiopathic PE is not well defined. We conducted a retrospective study of patients age 18 to 56 years who had idiopathic PE between 1994–2001.The incidence and cause of death within five years was determined using linked discharge records and a master death registry. A total of 3,456 patients had a first-time idiopathic PE. The rate of recurrent VTE 0–6 months after the index event was 13.1%/year, and 2.9%/year 6–60 months after the event. During the mean follow-up of 3.2 years 118 (3.4%, 95% confidence interval [CI]=2.8–4.1%) patients died. Fifty-two (44%) deaths occurred <29 days after the index PE (case-fatality rate =1.5%,95%CI=1.1–2.0%). Among the 66 cases (1.9%) that died after 28 days, 18 (0.52%) were due to recurrent PE or its sequelae: eight had recurrent PE alone, five had recurrent PE and a serious co-morbid illness, and five had thromboembolic pulmonary hypertension with or without acute PE. The person-time rate of death (deaths per 100 patientyears) attributed to any recurrent thromboembolism 6–60 months after the event was 0.16% (95%CI=0.1–0.26%). Ten of the 18 (56%) late thromboembolic deaths reflected a first-time recurrent PE. The 28-day case-fatality rate for recurrentVTE was 2.8% (95%CI= 1.5–4.9%).In this cohort of younger patients with idiopathic PE, the rate of death due to recurrentVTE, particularly to first-time recurrent PE, was low. Among the patients who died of thromboembolism >28 days after the index PE, 28% had developed pulmonary hypertension.

Keywords

Thromboembolism - epidemiology - PE - venous thrombosis - administrative data

Full Text

References

References
1 Kearon C. Natural history of venous thromboembolism. Circulation 2003; 107 (Suppl. 23) I22-30.
2 Aujesky D, Smith KJ, Roberts MS. Oral anticoagulation strategies after a first idiopathic venous thromboembolic event. Am J Med 2005; 118: 625-635.
3 Kearon C. Long-term management of patients after venous thromboembolism. Circulation 2004; 110 (Suppl. 09) I10-18.
4 Keeling D. Duration of anticoagulation: decision making based on absolute risk. Blood Rev 2006; 20: 173-178.
5 Cushman M, Tsai AW, White RH. et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 2004; 117: 19-25.
6 Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386-1389.
7 Piccioli A, Prandoni P, Goldhaber SZ. Epidemiologic characteristics, management, and outcome of deep venous thrombosis in a tertiary-care hospital: the Brigham and Women’s Hospital DVT registry. Am Heart J 1996; 132: 1010-1014.
8 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.
9 Janke RM, McGovern PG, Folsom AR. Mortality, hospital discharges, and case fatality for pulmonary embolism in the Twin Cities 1980-1995. J Clin Epidemiol 2000; 53: 103-109.
10 Stein PD, Kayali F, Olson RE. Estimated case fatality rate of pulmonary embolism, 1979 to 1998. Am J Cardiol 2004; 93: 1197-1199.
11 Heit JA, Mohr DN, Silverstein MD. et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160: 761-768.
12 Ageno W, Prandoni P, Romualdi E. et al. The metabolic syndrome and the risk of venous thrombosis: a casecontrol study. J Thromb Haemost 2006; 4: 1914-1918.
13 Douketis JD, Foster GA, Crowther MA. et al. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med 2000; 160: 3431-3436.
14 Iles S, Dalen JE. Clot burden and comorbidity in natural history of untreated pulmonary thromboembolism: Autopsy data in the trial by Barritt and Jordan. Chest 2003; 124: 1178-1179.
15 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (Suppl. 23) I4-8.
16 Douketis JD, Gu CS, Schulman S. et al. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med 2007; 147: 766-774.
17 White RH, Romano PS, Zhou H. et al. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158: 1525-1531.
18 White RH, Zhou H, Murin S. et al. Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996. Thromb Haemost 2005; 93: 298-305.
19 White RH, Dager WE, Zhou H. et al. Racial and gender differences in the incidence of recurrent venous thromboembolism. Thromb Haemost 2006; 96: 267-273.
20 Healthcare Costs and Utilization Project. Comorbidity Software, Version 3.1. 2005 Fiscal Year 2006. Cited April 3, 2006; Available from http://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp
21 Elixhauser A, Steiner C, Harris DR. et al. Comorbidity measures for use with administrative data. Med Care 1998; 36: 8-27.
22 Wilchesky M, Tamblyn RM, Huang A. Validation of diagnostic codes within medical services claims. J Clin Epidemiol 2004; 57: 131-141.
23 Alcalay A, Wun T, Khatri V. et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 2006; 24: 1112-1118.
24 Stukenborg GJP, Wagner DPP, Connors AFJMD. Comparison of the performance of two comorbidity measures, with and without information from prior hospitalizations. Med Care 2001; 39: 727-739.
25 Southern DA, Quan H, Ghali WA. Comparison of the Elixhauser and Charlson/Deyo methods of comorbidity measurement in administrative data. Med Care 2004; 42: 355-360.
26 White RH, Beyth RJ, Zhou H. et al. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999; 107: 414-424.
27 DeanAG, SullivanKM, Soe MM. OpenEpi: Open Source Epidemiologic Statistics for Public Health, 2007. Cited; Version 2.2: Available from www.OpenEpi.com
28 Murin S, Romano PS, White RH. Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost 2002; 88: 407-414.
29 Tapson VF, Humbert M. Incidence and prevalence of chronic thromboembolic pulmonary hypertension: From acute to chronic pulmonary embolism. Proc Am Thorac Soc 2006; 3: 564-567.
30 Pengo V, Lensing AWA, Prins MH. et al. Incidence of Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism. N Engl J Med 2004; 350: 2257-2264.
31 Mayo JR, Remy-Jardin M, Muller NL. et al. Pulmonary embolism: prospective comparison of spiral CT with ventilation-perfusion scintigraphy. Radiology 1997; 205: 447-452.
32 Kraaijenhagen RA, Lensing AWA, Wallis JW. et al. Diagnostic management of venous thromboembolism. Bailliere’s Clin Haematol 1998; 11: 541-586.
33 White TM, Kellis DS, Hightower SF. Conformance of clinical practice to established recommendations for the diagnosis and treatment of venous thromboembolic disease: Robin revisited. Am J Med Qual 1994; 9: 153-157.
34 Prandoni P, Noventa F, Ghirarduzzi A. 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.
35 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.
36 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.