Emerging Biomarkers for Assessing Thrombotic Risk in Patients Receiving Direct Oral Anticoagulants (DOACs).

Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline

Scientific and Standardization Committee Communication: Guidance document on the periprocedural management of patients on chronic oral anticoagulant therapy: Recommendations for standardized reporting of procedural/surgical bleed risk and patient‐specific thromboembolic risk

Direct Oral Anticoagulant Versus Low Molecular Weight Heparin for the Treatment of Cancer-Associated Thromboembolism: 2021 Updated Meta-Analysis of Randomized Controlled Trials

Safe and Effective Use of Rivaroxaban for Treatment of Cancer Associated Venous Thromboembolic Disease

Bleeding risk of intramuscular injection of COVID‐19 vaccines in adult patients with therapeutic anticoagulation

Clinical Outcomes of Cancer-Associated Venous Thromboembolism in Patients with Gastrointestinal or Genitourinary Cancers Treated with Direct Oral Anticoagulant Vs. Low Molecular Weight Heparin

BackgroundLow-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT.MethodsWe searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications.ResultsWe identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42–0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40–0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11–2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54–1.01). Both DOAC (HR 0.42; 95% CI 0.29–0.61) and LMWH (HR 0.57; 95% CI 0.44–0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding.ConclusionsDOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient’s bleeding risk, including cancer site, and patient’s values and preferences.

Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer.

BackgroundPatients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.ObjectiveA systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.Data SourcesMEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.Study SelectionRandomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.Data ExtractionIndependent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.Data SynthesisSeven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.ConclusionsVKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.

Cancer-associated thrombosis (CAT) is a common complication in patients with malignancy. Although direct oral anticoagulants (DOACs) have emerged as a treatment option for CAT, there have not been head-to-head comparisons of these agents. We searched MEDLINE and EMBASE from inception to April 2020 for studies comparing the effect of different long-term anticoagulation strategies for venous thromboembolism (VTE) in patients with cancer. We performed a network meta-analysis comparing the antithrombotic strategies in the selected studies using random-effects model. We identified a total of 20 studies [9 randomized control trials (RCTs) and 11 subgroup analyses from other unique RCTs] with total of 6699 patients for inclusion in our analysis. There was no significant difference in recurrent VTE, all-cause death, major bleeding and clinically relevant non-major bleeding among DOACs. When DOACs were combined, recurrent VTE was significantly decreased in DOACs compared to low-molecular weight heparin (LMWH) and Vitamin K antagonist (VKA) [RR (95% CI) 0.75 (0.59-0.94); RR (95% CI) 0.51 (0.39-0.66), respectively] without significant increase in major bleeding or clinically relevant non-major bleeding. In patients with CAT, there was no significant difference in recurrent thrombotic event among different DOACs. Bleeding risk was comparable among all anticoagulation strategies. When DOACs were combined, DOACs were associated with a significant decrease in recurrent VTE with comparable bleeding risk to LMWH and VKA.

Direct Oral Anticoagulants in Sickle Cell Disease, Where We Stand and Where We Are Heading: A Systematic Review

Introduction: Inherited thrombophilia screening is widely performed in patients with venous thromboembolism (VTE). Although recent studies suggest that direct oral anticoagulants (DOACs) may provide comparable efficacy and safety to Vitamin K antagonists (VKAs) in this population, robust evidence to support their extensive use is still lacking. We aimed to evaluate the rates of VTE recurrence and overall bleeding in patients with inherited thrombophilia treated with DOACs versus VKAs, with particular interest in those with severe thrombophilia.Methods: Using the electronic database of the largest healthcare provider in Israel, we conducted a retrospective search for patients with a recorded VTE between 2012 and 2021 (the index event). Patients aged 18 or older at the time of diagnosis were included if they began treatment with either a DOAC or a VKA within 30 days of the index event, provided they had laboratory evidence of inherited thrombophilia. Patients were followed up for two independent outcomes (VTE recurrence and overall bleeding) until December 31, 2022 or until termination of follow-up due to death, switching from one oral anticoagulation class to another, or discontinuation of oral anticoagulation. Rates of VTE recurrence and overall bleeding were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).Results: A total of 398 patients (median age 50.9±17.8, males 51.8%, severe thrombophilia 24.9%) were included. Among these, 230 patients (57.8%) were prescribed DOACs, while 168 patients (42.2%) received VKAs. The median follow-up for VTE recurrence and overall bleeding was 21.1 months and 20 months, respectively. Using the VKAs group as a reference, the hazard ratio for VTE recurrence on DOACs was 1.25 (95% CI, 0.23-6.7), and the hazard ratio for overall bleeding on DOACs was 0.33 (95% CI, 0.03-3.7). Restricting the analysis to 99 patients with severe thrombophilia (46 on DOACs, 53 on VKAs) showed no substantial differences in both efficacy and safety.Conclusions: Among patients with inherited thrombophilia treated with DOACs or VKAs, this study found no significant difference in the risk of recurrent VTE and observed a non-significant trend toward a lower risk of bleeding with DOACs.

Introduction: Direct oral anticoagulants (DOACs) are indicated for prevention of stroke in non-valvular atrial fibrillation (AF) and for both treatment and prevention of recurrence of venous thromboembolism (VTE). Very little is known about efficacy and safety of these agents in patients identifying as Black or African-American (AA), as landmark trials demonstrating their non-inferiority to vitamin K antagonists (VKAs) are notable for discrepancies in enrollment by patient’s race. As the primary efficacy and safety outcomes for both AF and VTE are similar, we hypothesized that the cumulative efficacy and safety of DOACs in AA patients would be similar to that of the general population. Methods: A systematic review was conducted of clinical trials that investigated the comparison between DOACs and VKAs in patients for both AF and VTE. The Mantel-Haenszel Method was used to estimate pooled risk ratios (RRs) and corresponding confidence intervals (CIs) for the efficacy and safety of DOACs in AAs compared to the general population. Primary efficacy outcome was defined as stroke or systolic embolism in AF or symptomatic, recurrent VTE. Primary safety outcome was defined as major bleeding in both AF and VTE. Results: Nine studies were used for meta-analysis, with 26 eliminated due to lack of randomization or subgroup data for AAs. A total of 80,688 of patients were analyzed with 1.67% being AA. Regarding efficacy, the RR for AAs using DOACs compared to VKAs was 0.98 (95% CI 0.62,1.55; I 2 =0%; p=0.94), while the RR for the entire population was 0.90 (CI 0.78,1.04; I 2 =41%; p=0.1). Regarding safety, the RR for AAs using DOACs compared to VKAs was 0.83 (CI 0.56,1.25; I 2 =0%; p=0.92), while the RR for the entire population was 0.78 (CI 0.65,0.93; I 2 =76%; p&lt;0.01). Conclusions: The use of DOACs versus VKAs in AF and VTE for AAs results in similar efficacy to the general population. DOACs are non-inferior to VKAs with respect to safety outcomes in AF and VTE for AAs. It is uncertain why superiority of safety outcomes seen in the general population are not seen in the AA population, and will require further studies.

Efficacy and Safety of Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism

Anticoagulant therapy for splanchnic vein thrombosis