Clinically relevant bleeding in cancer patients treated for venous thromboembolism from the CATCH study

Abstract

Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg once daily or warfarin (target International Normalized Ratio [INR] of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of < 3.0. A lower time in therapeutic range was associated with a higher risk of CRB. Conclusions CRB is a frequent complication in cancer patients with VTE during anticoagulant treatment, and is associated with age > 75 years and intracranial malignancy.

Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism

“…There is a gap in knowledge of predictive variables for MB in active cancer patients that was addressed by the RIETE group’s bleed risk stratification of the general population which included all cancer (OR = 1.7, 95%CI: 1.4-2.2) among others clinical risk items, receiving LMWH plus VKA[42]. Kamphuisen et al[43] on behalf of the CATCH trial presented the first pre-specified second analysis were a metastatic stage, older age (> 75 years old) and intracranial lesions described on clinical risk considerations in CAVTE with LMWH (tinzaparin) for major bleed. We found that active systemic treatment and active smoker significantly contributed to treatment failure, regardless of the therapy modality or packs per year smoked, respectively (Table 4).…”

Treatment and Prevention of Cancer-Associated Thrombosis in Frail Patients: Tailored Management

“…Factors associated with the risk of bleeding include thrombocytopenia caused by chemotherapy [22] while age >75 was identified as significant risk factor of CRB (RR 1.79 (95% CI 1.18–2.70) p = 0.013) [23].…”

Gastrointestinal Malignancies and Venous Thromboembolic Disease: Clinical Significance and Endovascular Interventions

“…In the secondary analysis of the CATCH trial, there was a 15.3% incidence rate of clinically relevant bleeding in patients treated with either LMWH or warfarin over a 6month period. 34 In comparison to LMWH, DOACs have shown a similar rate of bleeding in a large, retrospective analysis (13 vs. 11%; p ¼ 0.746). 35 The anticoagulation management of GI-cancer associated VTE is even more challenging when patients are thrombocytopenic, which is relatively common when patients are treated with chemotherapy.…”