Effectiveness and safety of anticoagulants for the treatment of venous thromboembolism in patients with cancer

Abstract

Anticoagulation is used to treat venous thromboembolism (VTE) in cancer patients, but may be associated with an increased risk of bleeding. VTE recurrence and major bleeding were assessed in cancer patients treated for VTE with the most currently prescribed anticoagulants in clinical practice. Newly diagnosed cancer patients (first VTE 1/1/2013‐05/31/2015) who initiated rivaroxaban, low‐molecular‐weight heparin (LMWH), or warfarin were identified from Humana claims data and observed until end of eligibility or end of data availability. VTE recurrence was a hospitalization with a primary diagnosis of VTE ≥7 days after first VTE. Major bleeding events on treatment were identified using validated criteria. Cohorts were compared using Kaplan–Meier rates at 6 and 12 months and Cox proportional hazards models. Cohorts were adjusted for their differences at baseline. A total of 2428 patients (rivaroxaban: 707; LMWH: 660; warfarin: 1061) met inclusion criteria. Patient characteristics were well balanced after weighting. There was a trend for lower VTE recurrence rates in rivaroxaban users compared to LMWH users at 6 months (13.2% vs. 17.1%; P = .060) and significantly lower at 12 months (16.5% vs. 22.2%; P = .030) [HR: 0.72, 95% CI: (0.52‐0.95); P = .024]. VTE recurrence rates were also lower for rivaroxaban than warfarin users at 6 months (13.2% vs. 17.5%; P = .014) and 12 months (15.7% vs. 19.9%; P = .017) [HR: 0.74, 95% CI: (0.56‐0.96); P = .028]. Major bleeding rates were similar across cohorts. This real‐world analysis suggests cancer patients with VTE treated with rivaroxaban had significantly lower risk of recurrent VTE and similar risk of bleeding compared to those treated with LMWH or warfarin.

Role of direct oral anticoagulants in the treatment of cancer‐associated venous thromboembolism: guidance from the SSC of the ISTH

“…For instance, a single‐institution cohort study limiting rivaroxaban use to patients without active gastrointestinal tract or urinary tract lesions and performing empirical dose reduction in elderly patients has reported rates of major bleeding and recurrent VTE of 2.2% (95% CI 0–4.2%) and 4.4% (95% CI 1.4–7.4%), respectively . Similarly, in a large US claims dataset of 2428 patients, there were lower rates of recurrent VTE in rivaroxaban users than in LMWH users at 6 months (13.2% versus 17.1%; P = 0.06) and 12 months (16.5% versus 22.2%; P = 0.03) (HR 0.72, 95% CI, 0.52–0.95; P = 0.02), without any differences in major bleeding . A recently published systematic review of the literature describing all observational studies on this topic reported that most studies used rivaroxaban and enoxaparin .…”

Use of Direct Oral Anticoagulants in Patients with Cancer: Practical Considerations for the Management of Patients with Nausea or Vomiting

“…Several subanalyses and meta‐analyses of data from RCTs have found similar efficacy and safety outcomes with DOACs and VKAs or standard therapy in patients with cancer (Table ). In a large‐scale meta‐analysis, Brunetti et al compared the efficacy and safety of DOACs with those of conventional treatment with either a VKA (seven trials) or LMWH (two trials) in 1,952 patients with VTE and cancer .…”

“…When DOACs were compared with VKAs and LMWHs separately, DOACs were associated with higher rates of bleeding than LMWHs but were found to be as effective as and to have a similar safety profile to VKAs . Data from retrospective or observational studies in patients with cancer and VTE seem to indicate that DOACs have a similar efficacy and tolerability profile (including the risk of major bleeding) to LMWHs (Table ) . The vast majority of these clinical data was collected when specific reversal agents for the DOACs were not available.…”

The risk of recurrent VTE and major bleeding in a commercially‐insured population of cancer patients treated with anticoagulation

“…Recently, a real‐world study of primarily Medicare‐insured patients compared the risk of recurrent venous thromboembolism (VTE) and major bleeding associated with rivaroxaban, warfarin, and low‐molecular weight heparin (LMWH) following a first‐episode of VTE among patients with cancer . Results suggested that rivaroxaban treatment is associated with a lower risk of recurrent VTE versus LMWH or warfarin, and that the rate of major bleeding does not significantly differ across treatments .…”