Venous and arterial thromboembolism after colorectal cancer in the Netherlands: Incidence, predictors, and prognosis.

BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer type. CRC-patients are at increased risk of venous and arterial thromboembolism (TE), but the magnitude of the risks, their predictors and consequences are not exactly known. OBJECTIVES: We aimed to determine incidence, predictors and prognosis of TE after incident CRC in a large, unselected population. METHODS: Using data from Statistics Netherlands and the Netherlands Comprehensive Cancer Organization, all incident CRC-patients were identified between 2013 and 2018 plus a sample of 1:2 age- and sex-matched control subjects. Incidence rates and cumulative incidences for TE were estimated. Predictor variables for TE were explored by univariable Cox regression. The association between TE and all-cause mortality was evaluated by multivariable time-dependent Cox regression. RESULTS: 68,238 incident CRC-patients were matched to 136,476 controls. CRC-patients had a 1-year cumulative venous TE (VTE) incidence of 1.93 % (95%CI 1.83-2.04), versus 0.24 % (95%CI 0.21-0.27) in controls (HR 8.85; 95%CI 7.83-9.99). For arterial TE (ATE), this was 2.74 % (95%CI 2.62-2.87) in CRC versus 1.88 % (95%CI 1.81-1.95) in controls (HR 1.57; 95%CI 1.47-1.66). Cancer stage, surgery, chemotherapy and asthma were predictors for VTE, whereas age, prior ATE and Parkinson's disease were predictors for ATE. CRC patients with TE had an increased risk of all-cause mortality (VTE HR; 3.68 (95%CI 3.30-4.10, ATE HR; 3.05 (95%CI 2.75-3.39)) compared with CRC-patients without TE. CONCLUSIONS: This Dutch nationwide cohort study adds detailed knowledge on the risk of VTE and ATE, their predictors and prognosis in CRC-patients. These findings may drive TE prophylactic management decisions.

[Continued anticoagulation for unprovoked venous thromboembolism: guidance through the maze of recent studies]. / Langdurige antistolling na veneuze trombo-embolie.

Recent American, European and Dutch guidelines recommend indefinite anticoagulation after a diagnosis of unprovoked venous thromboembolism in the absence of a high bleeding risk. The recommended approach would be to only stop anticoagulant therapy after three months in patients with one or more untreatable risk factors for bleeding such as prior major bleeding, uncorrectable hypertension or deep thrombocytopenia. Vitamin K-antagonists and direct oral anticoagulants (DOACs) were found to protect against recurrent venous thromboembolism at cost of major bleedings, although at a lower frequency than the number of prevented thrombotic events. Due to the lower risk of major bleeding than associated with vitamin K-antagonists, DOACs are the preferred treatment option for the long term treatment of unprovoked venous thromboembolism. Apixaban is available in a reduced dose for long-term treatment, and rivaroxaban in a reduced dose was recently shown to be more effective than aspirin.

Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism.

INTRODUCTION: Treatment of acute venous thromboembolism (VTE) in cancer patients is challenging, owing to a high risk of recurrent VTE and bleeding complications. The anticoagulants of choice are low molecular weight heparins (LMWHs), because of a proven higher efficacy than vitamin K antagonists (VKAs) and a similar bleeding profile. The recently introduced new oral anticoagulants (NOACs) have the potential to be alternative options for these patients, as these drugs share practical advantages with LMWH, are administered orally, and had similar efficacy to VKAs but a lower bleeding risk in phase 3 studies in the general VTE population. METHODS: A systematic literature search was performed to identify phase 3 trials investigating NOACs for the treatment of VTE. The efficacy outcome was recurrent VTE, and the safety outcome was major and clinically relevant non-major bleeding. Pooled incidence rates and risk ratios (RRs) were calculated for cancer patients and non-cancer patients separately. RESULTS AND DISCUSSION: Five studies were included, with 19 060 patients, of whom 973 (5.1%) had active cancer. The pooled incidence rates of recurrent VTE were 4.1% (95% confidence interval [CI] 2.6-6.0) in cancer patients treated with NOACs, and 6.1% (95% CI 4.1-8.5) in patients treated with VKAs (RR 0.66, 95% CI 0.38-1.2). The pooled incidence rates of major or non-major clinically relevant bleeding were 15% (95% CI 12-18) in cancer patients treated with NOACs, and 16% (95% CI 9.9-22) in patients treated with VKAs (RR 0.94, 95% CI 0.70-1.3). These results form a solid basis for the initiation of a head-to-head comparison of NOACs with LMWH in cancer patients.

Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.

INTRODUCTION: New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE. METHODS: We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models. RESULTS: Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban. CONCLUSIONS: NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.