Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study.

Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism (VTE) in cancer patients, but they have not been compared with low-molecular-weight heparin (LMWH), the current recommended treatment for these patients. The Hokusai VTE-cancer study is a randomised, open-label, clinical trial to evaluate whether edoxaban, an oral factor Xa inhibitor, is non-inferior to LMWH for treatment of VTE in patients with cancer. We present the rationale and some design features of the study. One such feature is the composite primary outcome of recurrent VTE and major bleeding during a 12-month study period. These two complications occur frequently in cancer patients receiving anticoagulant treatment and have a significant impact. The evaluation beyond six months will fill the current gap in the evidence base for the long-term treatment of these patients. Based on the observation that the risk of recurrent VTE in patients with active cancer is similar to that in those with a history of cancer, the Hokusai VTE-cancer study will enrol patients if whose cancer was diagnosed within the past two years. In addition, patients with incidental VTE are eligible because their risk of recurrent VTE is similar to that in patients with symptomatic disease. The unique design features of the Hokusai VTE-cancer study should lead to enrolment of a broad spectrum of cancer patients with VTE who could benefit from oral anticoagulant treatment.

Oral rivaroxaban for the treatment of symptomatic pulmonary embolism.

BACKGROUND: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. METHODS: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

The association of masked hypertension in treated type 2 diabetic patients with carotid artery IMT.

OBJECTIVES: To evaluate the association of masked hypertension (MH) in treated type 2 diabetic patients without history of cardiovascular disease with carotid artery target organ damage. METHODS: Sixty-four type 2 diabetic patients treated for hypertension with office BP below 140/90 mm Hg were examined by 24-h BP monitoring and carotid sonography. MH was diagnosed if daily mean ambulatory BP was >or=135/85 mm Hg. The association of MH with carotid artery parameters was evaluated. RESULTS: The average age of patients was 62+/-5 years. Twenty-four patients had MH (37.5%). Carotid artery IMT was 0.74+/-0.08 mm in patients with MH and 0.69+/-0.06 mm without MH (p=0.03). The distensibility of common carotid artery was 0.24+/-0.07 mmHg(-1) in patients with MH and 0.29+/-0.1mm Hg(-1) without MH (p=0.14). After adjustment for age, gender, smoking, duration of diabetes, BMI and clinic blood pressure (BP) values the association of MH with carotid artery IMT was sustained. CONCLUSION: Masked hypertension in treated type 2 diabetic patients is associated with carotid artery IMT.

Spontaneous jugular vein thrombosis.

Jugular vein thrombosis (JVT) is usually secondary to central venous catheterisation, distant malignancy, hypercoagulable state or ovarian hyperstimulation syndrome. Spontaneous internal JVT is an extremely rare entity. A 61-year-old man presented with swelling of the right side of his face. An ultrasonographic scan showed thrombosis of the right jugular vein. Clinical tests, including oncomarkers, X-ray, CT scan and abdominal ultrasonography, searching for malignancy, were negative. The patient was heparinized immediately using LMWH and then underwent warfarin anticoagulation therapy for 6 months. One year later the patient was in good clinical condition with no malignancy diagnosed. Aetiology and the treatment of spontaneous JVT are discussed.