Sudeep Shivakumar

Aspirin after an initial short course of rivaroxaban has been shown to be safe and effective for the prevention of venous thromboembolism after total hip or total knee arthroplasty, but uncertainty remains about the use of aspirin alone. In this multicenter, double-blind, randomized, controlled trial, we assigned patients to receive once-daily thromboprophylaxis with either 81 mg of aspirin or 10 mg of oral rivaroxaban for the first 5 days after total hip or total knee arthroplasty. All the patients then received further thromboprophylaxis with 81 mg of aspirin daily for 9 additional days after knee arthroplasty and for 30 additional days after hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism, which consisted of either proximal deep-vein thrombosis or pulmonary embolism (primary effectiveness outcome), and for bleeding complications (primary safety outcome). The noninferiority margin for aspirin alone as compared with rivaroxaban-aspirin was 0.7 percentage points. A total of 5429 patients underwent randomization. Venous thromboembolism developed in 13 of 2718 patients (0.48%) in the aspirin-alone group and in 12 of 2647 patients (0.45%) in the rivaroxaban-aspirin group (risk difference, 0.02 percentage points; 95% confidence interval [CI], -0.34 to 0.39; P<0.001 for noninferiority). Major bleeding or clinically relevant nonmajor bleeding events occurred in 45 of 2718 patients (1.66%) in the aspirin-alone group and in 54 of 2647 patients (2.04%) in the rivaroxaban-aspirin group (risk difference, -0.38%; 95% CI, -1.11 to 0.34). After total hip and total knee arthroplasty, the use of aspirin alone was not inferior to a strategy of using rivaroxaban followed by aspirin for the prevention of symptomatic venous thromboembolism, with no clinically relevant difference in bleeding events. (Funded by the Canadian Institutes of Health Research; EPCAT III ClinicalTrials.gov number, NCT04075240.).

Background: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. The AVERT trial showed apixaban thromboprophylaxis reduced VTE in intermediate‐to‐high‐risk patients initiating chemotherapy. However, the efficacy and safety of apixaban according to baseline chemotherapy class remain incompletely characterized. Methods: We conducted a post hoc analysis stratified by chemotherapy class of the randomized, double‐blind, placebo‐controlled AVERT trial comparing apixaban (2.5 mg twice daily) with placebo in ambulatory cancer patients initiating chemotherapy. The primary efficacy outcome was VTE, and the primary safety outcome was clinically relevant bleeding (major or clinically relevant non major bleeding (CRNMB)) per ISTH criteria. A subgroup analysis compared platinum‐based with non‐platinum chemotherapy. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CI), adjusted for age, sex, and study site. Treatment‐by‐platinum interaction terms were used to assess effect modification by platinum exposure. Results: A total of 563 patients were included and categorized by one or more chemotherapy classes at randomization. Compared with placebo, apixaban appeared to reduce VTE in patients on platinum (HR 0.30, 95% CI 0.16–0.57), taxane (HR 0.42, 95% CI 0.23–0.75), taxane‐platinum (HR 0.28, 95% CI 0.12–0.68), topoisomerase inhibitor (HR 0.32, 95% CI 0.19–0.53), and antimetabolite regimens (HR 0.25, 95% CI 0.12–0.54), without increased bleeding. Among placebo‐treated patients, platinum‐based chemotherapy was associated with a higher risk of VTE compared with non‐platinum regimens (HR 2.25, 95% CI 1.48–3.42), whereas no statistically significant difference was observed among apixaban‐treated patients. Treatment‐by‐platinum interaction testing did not demonstrate significant effect modification by platinum exposure. Conclusion: In this exploratory, hypothesis‐generating analysis, apixaban thromboprophylaxis was associated with reduced VTE across several chemotherapy regimens with generally acceptable safety outcomes. Patients receiving platinum‐based chemotherapy may derive greater absolute benefit from thromboprophylaxis in the setting of higher underlying thrombotic risk.

Venous thromboembolism is a serious medical complication with an increased risk in patients with multiple myeloma undergoing combination treatment regimens. Acetylsalicylic acid is routinely used as a method of thromboprophylaxis in multiple myeloma patients treated with lenalidomide, and rivaroxaban has been assessed in small-scale studies in multiple myeloma patients treated with immunomodulatory drugs; yet, no study has compared the two methods. In this pilot, we asked if a full-scale trial would be feasible to assess the benefits of rivaroxaban over acetylsalicylic acid as a thromboprophylactic approach. This pilot recruited patients with multiple myeloma on lenalidomide-based therapy and randomized them to either low-dose acetylsalicylic acid or rivaroxaban, then monitored bleeding and thrombotic events throughout lenalidomide–dexamethasone treatment. A total of 55 patients were recruited across three Canadian centres, with two venous thromboembolic events and two bleeding events, all in the acetylsalicylic acid arm. We conducted a post hoc analysis of active recruitment time as a definition of recruitment feasibility, as we did not achieve our pre-defined feasibility goals. Despite the challenges in enrollment, possibly due to social restrictions during the COVID-19 pandemic, we maintain that a full-scale trial is feasible and offers insight into thromboprophylactic management in this population.

Cancer-associated venous thromboembolism is a devastating complication of cancer and is associated with significant morbidity and mortality. The cornerstone of cancer-associated venous thromboembolism treatment is anticoagulation, and in recent years, there have been notable randomized clinical trials that have revealed insights into the efficacy and safety of direct oral anticoagulants and low-molecular-weight heparin in the treatment of cancer-associated thrombosis. Deciding on the ideal anticoagulation treatment plan for a patient with a cancer-associated thrombosis is a complex task that requires an understanding of clinical trial data, society guidelines, and, most importantly, consideration of many cancer-related, treatment-related, and patient-related factors. This article summarizes important factors to consider when deciding on anticoagulation therapy for a patient with cancer-associated thrombosis.

Objective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. Setting University based emergency departments or outpatient clinics in Canada. Participants Patients with symptoms or signs of DVT. Intervention DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer 1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main outcome measure Symptomatic venous thromboembolism at three months. Results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference −0.64, 95% confidence interval −0.68 to −0.60), corresponding to a relative reduction of 47%. Conclusions The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. Registration ClinicalTrials.gov NCT02038530.

Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications. Risks vary significantly between individuals based on cancer status, treatment, and other characteristics. To facilitate the evidence-based management of anticoagulant therapy in this patient population, a committee of 11 Canadian clinical experts updated a consensus-based algorithm for the acute and extended treatment of symptomatic and incidental CAT that was developed in 2018. Following a systematic review of the literature, updates to the algorithm were discussed during an online teleconference, and the algorithm was subsequently refined based on feedback from committee members. Clinicians using this treatment algorithm should consider bleeding risk, type of cancer, and drug–drug interactions, as well as patient and clinician preferences, in tailoring anticoagulation for patients with CAT. Anticoagulant therapy should be adapted as the patient’s cancer status and management change over time.