Incidence of Recurrent Thromboembolic and Bleeding Complications Among Patients With Venous Thromboembolism in Relation to Both Malignancy and Achieved International Normalized Ratio: A Retrospective Analysis

TLDR

Heparin followed by vitamin K antagonists is the standard treatment for venous thromboembolism, yet it is unclear whether malignancy increases the risk of recurrence or bleeding and how the achieved INR influences these events. This study aimed to determine the incidence of venous thromboembolic recurrence and major bleeding in VTE patients relative to malignancy status and achieved INR levels. Using a retrospective analysis of 1,303 patients from two multicenter randomized trials, patients received initial heparin (standard or low‑molecular‑weight) followed by vitamin K antagonists within one day, targeting an INR of 2.0–3.0 for three months. Patients with malignancy experienced significantly higher recurrence (27.1 vs 9.0 per 100 patient‑years) and bleeding rates (13.3 vs 2.1 per 100 patient‑years), and both groups had lower event rates when INR exceeded 2.0, yet overall complications remained higher in the malignant cohort.

Abstract

Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR.In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0.In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0.Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.