Direct Oral Anticoagulants for the Prevention and Acute Treatment of Cancer-Associated Thrombosis.

Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15-25% of all VTE cases. For decades, the standard treatment for CAT used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score ≥2 prior to starting new chemotherapy, low bleeding risk, no interfering medications).

Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study.

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non-SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.

Prevention of post-thrombotic syndrome with rosuvastatin: A multicenter randomized controlled pilot trial (SAVER).

BACKGROUND: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS. METHODS: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female. RESULTS: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (-3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59). CONCLUSION: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02679664.

Statins for venous event reduction in patients with venous thromboembolism: A multicenter randomized controlled pilot trial assessing feasibility.

BACKGROUND: Statins may reduce the risk for recurrent venous thromboembolism (VTE); however, no randomized trials have explored this hypothesis. We performed a pilot randomized trial to determine feasibility of recruitment for a larger trial of secondary VTE prevention with rosuvastatin. METHODS: Patients with a newly diagnosed symptomatic proximal deep vein thrombosis and/or pulmonary embolism, receiving standard anticoagulation, were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days or no rosuvastatin for 6 months. RESULTS: Between November 2016 and December 2019, 3391 patients were assessed for eligibility in six centers. Of these patients, 1347 (39.7%) were eligible and approached for participation in the trial and 312 (23.1%) were randomized. The mean rate of randomization was 8.2 ± 4.3 patients per month. During follow-up, five recurrent VTE events were observed, three (1.9%) in the rosuvastatin group (two pulmonary embolism, one deep vein thrombosis), and two (1.3%) in the control group (two pulmonary embolism; P = 0.68). One major arterial event occurred in the rosuvastatin arm and none in the control arm (0.6% vs. 0%, P = 0.50). CONCLUSION: This pilot trial supports the feasibility of a larger scale randomized controlled trial to determine the efficacy of adjuvant rosuvastatin for the secondary prevention of VTE.