Failure of the Ottawa Score to Predict the Risk of Recurrent Venous Thromboembolism in Cancer Patients: The Prospective PREDICARE Cohort Study

Abstract

Introduction Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients.

Methods In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism (PE) were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value of > 0.70 was needed to validate the Ottawa score.

Results A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, and VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), lower digestive tract (14.4%), and breast (13.9%) cancers. The Ottawa score was high (≥ 1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9–11.1) overall, and 5.0% (95% CI: 2.3–10.8) versus 9.1% (95%CI: 6.1–13.6) in the Ottawa low versus high risk groups, respectively. The C-statistic value was 0.60 (95% CI: 0.55–0.65).

Conclusion In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.

Keywords

cancer - LMWH - venous thromboembolism - recurrence - Ottawa score

• References

• 1 Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: burden, mechanisms, and management. Thromb Haemost 2017; 117 (02) 219-230
• 2 Lee AY, Levine MN, Baker RI. et al; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 (02) 146-153
• 3 Giustozzi M, Agnelli G, Del Toro-Cervera J. et al. Direct oral anticoagulants for the treatment of acute venous thromboembolism associated with cancer: a systematic review and meta-analysis. Thromb Haemost 2020; 120 (07) 1128-1136
• 4 Raskob GE, van Es N, Verhamme P. et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
• 5 Young AM, Marshall A, Thirlwall J. et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018; 36 (20) 2017-2023
• 6 Kraaijpoel N, Di Nisio M, Mulder FI. et al. Clinical impact of bleeding in cancer-associated venous thromboembolism: results from the Hokusai VTE cancer study. Thromb Haemost 2018; 118 (08) 1439-1449
• 7 Louzada ML, Carrier M, Lazo-Langner A. et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation 2012; 126 (04) 448-454
• 8 Delluc A, Miranda S, Exter PD. et al. Accuracy of the Ottawa score in risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis. Haematologica 2020; 105 (05) 1436-1442
• 9 van Es N, Louzada M, Carrier M. et al. Predicting the risk of recurrent venous thromboembolism in patients with cancer: a prospective cohort study. Thromb Res 2018; 163: 41-46
• 10 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 (04) 692-694
• 11 Prentice RL, Kalbfleisch JD, Peterson Jr AV, Flournoy N, Farewell VT, Breslow NE. The analysis of failure times in the presence of competing risks. Biometrics 1978; 34 (04) 541-554
• 12 den Exter PL, Kooiman J, Huisman MV. Validation of the Ottawa prognostic score for the prediction of recurrent venous thromboembolism in patients with cancer-associated thrombosis. J Thromb Haemost 2013; 11 (05) 998-1000
• 13 Di Nisio M, Valeriani E, Riva N, Schulman S, Beyer-Westendorf J, Ageno W. Anticoagulant therapy for splanchnic vein thrombosis: ISTH SSC Subcommittee Control of Anticoagulation. J Thromb Haemost 2020; 18 (07) 1562-1568
• 14 Kirkilesis G, Kakkos SK, Bicknell C, Salim S, Kakavia K. Treatment of distal deep vein thrombosis. Cochrane Database Syst Rev 2020; 4: CD013422
• 15 Robert-Ebadi H, Righini M. Should we diagnose and treat distal deep vein thrombosis?. Hematology (Am Soc Hematol Educ Program) 2017; 2017 (01) 231-236
• 16 Khorana AA, Kamphuisen PW, Meyer G. et al. Tissue factor as a predictor of recurrent venous thromboembolism in malignancy: biomarker analyses of the CATCH trial. J Clin Oncol 2017; 35 (10) 1078-1085