Oral Anticoagulants For Venous Thromboembolism Research Articles

Unapproved Dose of Direct Oral Anticoagulants for Venous Thromboembolism - Right or Wrong?

Unapproved Dose of Direct Oral Anticoagulants for Venous Thromboembolism - Right or Wrong?

HPR89 Payer Rejections and Prescription Abandonment Among Patients Newly Prescribed Oral Anticoagulants for Venous Thromboembolism

HPR89 Payer Rejections and Prescription Abandonment Among Patients Newly Prescribed Oral Anticoagulants for Venous Thromboembolism

The bridging conundrum: perioperative management of direct oral anticoagulants for venous thromboembolism

Most patients diagnosed with venous thromboembolism (VTE) are currently treated with direct oral anticoagulants (DOACs). Before an invasive procedure or surgery, clinicians face the challenging decision of how to best manage DOACs. Should the DOAC be held, for how long, and are there instances where bridging with other anticoagulants should be considered? Although clinical trials indicate that most patients taking DOACs for atrial fibrillation do not require bridging anticoagulation, the optimal strategy for patients with a history of VTE is undefined. In this review, we present a case-based discussion for DOAC interruption perioperatively in patients receiving anticoagulation for management of VTE.

Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA). We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8). For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.

Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project.

Venous thromboembolism (VTE) is a major cause of death in the world. After the acute-phase treatment, the optimal duration of anticoagulation is still debatable. The latest guidelines suggest maintaining long-term anticoagulation in patients with cancer-associated thrombosis (CAT) or with unprovoked VTE and a low bleeding risk. Methods: The MAC Project is an ongoing prospective-cohort, multi-center, observational study in Italy. The project aims to collect real-life clinical information in unselected patients given oral anticoagulants for VTE over a 5-year follow-up period. There were no exclusion criteria, except for life expectancy <6 months and refusal to sign the informed consent form or to attend the planned follow-up visit. All patients were followed-up prospectively with clinical controls scheduled at 3, 6, and 12 months after the index event, and then annually for up to 5 years. The primary efficacy and safety outcomes were symptomatic recurrent VTE and major bleeding. Results: We analyzed 450 consecutive patients treated with rivaroxaban and referred them to the MAC Project database for unprovoked or recurrent VTE. Of these, 267 (55%) were unprovoked VTE, and 377 (87%) were symptomatic. We followed up with the patients for a mean of 22 months (Q1 10.7; Q3 37.4 months). Recurrent VTE occurred in 12 patients on rivaroxaban treatment (IR 1.7 per 100 person-years). Males had more recurrence than women. During the follow-up period, we recorded 13 (2.9%) major bleeding, 12 (2.7%) clinically relevant non-major bleeding, 8 minor bleeding, and no fatal bleeding events. Overall, bleeding events occurred in 33 (7.3%) patients, most occurring within the first 2 years of treatment. In addition, we observed a statistically significant higher incidence of bleeding in patients with a baseline HAS-BLED score of 3 to 4 compared with those with a score of 0 to 2, with most events occurring during the first 3 months of treatment (RR 5.9). Discussion: Rivaroxaban appears to be safe and effective for the long-term treatment of patients with recurrent or unprovoked VTE. Our results match previously published data, and we are confident that the continuation of the follow-up for up to 5 years will confirm these outcomes.

Bleeding complications in patients on new oral anticoagulants for venous thromboembolism in Kenya.

The incidence of bleeding complications in patients with venous thromboembolism (VTE) on new oral anticoagulants (NOACs) has not been widely studied in contemporary clinical practice in Africa. The purpose of this study was to determine the rates of major bleeding, clinically relevant non-major bleeding (CRNM) and minor bleeding associated with NOAC use. A retrospective review was carried out of patients diagnosed with venous thromboembolism and treated with NOACs at the Aga Khan University Hospital, Nairobi, from January 2014 to December 2019. Clinical and outcome data were collected from medical records and the hospital mortality database. All patients with VTE aged > 18 years and initiated on NOACS were recruited. Patients with missing information were excluded. They were followed up from the time of commencement of oral anticoagulation to completion of therapy, or to the time of the first major bleed, CRNM or minor bleeding. Data on bleeding were obtained from the hospital database and through telephone interviews. Unadjusted rates of the first major bleeding event or CRNM were calculated as the number of bleeding events per 100 person-years. Two hundred and forty-three patients with VTE were recruited and 222 (91.4%) were initiated on rivaroxaban, 12 (4.9%) on dabigatran and nine (3.7%) on apixaban, with a median follow up of 213 [interquartile range (IQR): 119-477] days. The median age of the patients was 57 (IQR: 45-71) years. A total of 64 bleeding events were identified in 50 (20.6%) patients. Overall, the incidence rate for bleeding events was 17.24 per 100 patient-years. The incidence rate of major bleeding was 3.79 per 100 person-years. Gastrointestinal bleeding was the most common major bleeding site. There were more females with bleeding events (70.7%) compared to males. Anaemia and the use of aspirin and other antiplatelets were associated with a higher incidence of major and CRNM bleeding [relative risk (RR) = 3.77, confidence interval (CI) = 1.37-10.39, p = 0.005 and RR = 8.89, CI = 2.06-38.33, p = 0.0003, respectively]. Most of these bleeds were minor, with the gastrointestinal tract being the most common source of major bleeding and menorrhagia being the commonest cause of bleeding. Anaemia and the use of aspirin were associated with a higher incidence of major bleeding.

Effectiveness and safety of extended treatment with direct oral anticoagulants for venous thromboembolism in Japan: A retrospective cohort study using claims data

PurposeWe aimed to evaluate the risk of recurrent venous thromboembolism (VTE) among patients receiving direct oral anticoagulant (DOAC) therapy (extended and non-extended) using claims data. MethodsPatients treated with DOACs at the first VTE event were identified using Japanese claims data; Cox proportional hazard models were used to evaluate the risk of recurrence. Unadjusted, adjusted, and stabilized inverse probability treatment weighting (s-IPTW) analyses were used to assess the differences between patients treated for more than 90 days after the index date (extended treatment group) and those treated within 90 days (nonextended treatment group). Bleeding was assessed separately from recurrent VTE evaluation during the observation period. ResultsWe included 4,010 patients (mean age, 69 years; 57.9% females; extended: 2,684, nonextended: 1,326). After IPTW, all patient characteristics were well balanced. When the follow-up was censored at 18 months, the hazard ratio (extended/nonextended) for unadjusted, adjusted, and two s-IPTW analyses were 1.31 (P = 0.2762), 1.25 (P = 0.372), 1.32 (P = 0.2579), and 1.33 (P = 0.2498), respectively. The proportions of those who experienced intracranial, gastrointestinal, respiratory, and renal/urinary tract bleeding during the observation period in both groups were 2.9% vs. 3.8%, 2.1% vs. 2.3%, 1.0% vs. 0.5%, and 1.4% vs. 0.7% (extended vs. nonextended), respectively. ConclusionsThere were no differences in VTE recurrence between the two groups. In clinical practice and with a risk-benefit evaluation, both VTE treatment types were well controlled. Further evaluation is required, considering patient background within the observation period of 90 days and safety of treatment for bleeding events.

Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60-89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: NCT03045406.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism: a meta-analysis.

ObjectiveSeveral trials had compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin for acute venous thromboembolism, but the results were incomplete. This updated review comprehensively assessed the efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism.DesignMeta-analysis of randomised control trials. Six databases were searched from January 2000 to December 2018.SettingAdult patients had got non-vitamin K antagonist oral anticoagulants or warfarin for venous thromboembolism.ParticipantsRandomised control trials that compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin.Main outcome measuresThe efficacy and safety of non-vitamin K antagonist oral anticoagulants .ResultsSeven studies involving 29,879 cases were included, among which 14,943 cases were assigned to non-vitamin K antagonist oral anticoagulants group and 14,936 cases to warfarin group. Meta-analysis showed that compared with warfarin, recurrent venous thromboembolism (odds ratio 0.94 [95% confidence interval 0.81 to 1.11]), death related to venous thromboembolism or fatal pulmonary embolism (odds ratio 1.00 [95% confidence interval 0.63 to 1.60]), symptomatic deep-vein thrombosis (odds ratio 0.88 [95% confidence interval 0.72 to 1.09]), symptomatic nonfatal pulmonary embolism (odds ratio 1.03 [(95% confidence interval 0.82 to 1.30]) and all deaths (odds ratio 0.92 [95% confidence interval 0.76 to 1.12]) are similar in non-vitamin K antagonist oral anticoagulants group, but major bleeding event (odds ratio 0.61 [95% confidence interval 0.50 to 0.75]) and clinically relevant non-major bleeding event (odds ratio [95% confidence interval 0.53 to 0.85]) are less in non-vitamin K antagonist oral anticoagulants group. ConclusionsFor the treatment of venous thromboembolism, non-vitamin K antagonist oral anticoagulants is as effective as warfarin, and has a better safety profile than warfarin.

Anticoagulant treatment satisfaction with warfarin and direct oral anticoagulants for venous thromboembolism

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen’s d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p < 0.0001) and ACTS Benefits scores (10.21 v. 9.84, p = 0.046) for DOACs vs. warfarin, respectively. The magnitude of the difference was small (Cohen’s d of 0.29 for ACTS Burdens and 0.12 for ACTS Benefits). Patients taking DOACs for venous thromboembolism were on average more satisfied with anticoagulant treatment than were warfarin users, although the magnitude of the difference was small.

MAC Project-Monitoring Anticoagulant Therapy Observational Study: Rationale and Protocol.

Real-life studies complement data from registrative trials. Because of the delayed registration of direct oral anticoagulants in Italy, scarce real-life data on such treatments is available for the Italian population. The aim of the MAC project is to collect real-life clinical information in unselected patients given oral anticoagulants for venous thromboembolism, during a 5-year follow-up period. This is a prospective-cohort, multi-center, observational study performed in four Italian centers. The estimated samples size is 4,000 patients. The efficacy outcomes are: incidence of symptomatic recurrent venous thromboembolism and of post-thrombotic syndrome. The safety outcomes are: incidence of major bleeding, clinically relevant non-major bleeding, minor bleeding, serious adverse events, and mortality. The MAC project has the potential to improve our understanding of the epidemiology and of the therapeutic strategies adopted in Italian patients with venous thromboembolism.Clinical Trial Registration: WWW.ClinicalTrials.Gov, identifier: NCT0432939.

S0015 Oral Anticoagulants for Venous Thromboembolism (VTE) in Pancreatic Cancer: Friend or Foe

INTRODUCTION: Metastatic pancreatic carcinoma (MPC) has traditionally been associated with a higher risk of venous thromboembolism (VTE). However, the relative safety and efficacy of enoxaparin (approved therapy) and conventional medications such as oral anticoagulants (OAC) have never been reported in these patients. METHODS: A single-center retrospective cohort study was performed from January 2017 till March 2019. All patients with a confirmed diagnosis of MPC induced VTE were included. An unadjusted odds ratio (OR) was computed to determine the rate of mortality, adverse events of medications and recurrence of VTE. RESULTS: A total of 835 charts were reviewed and 38 patients were included in the analysis. The mean age was 69.9 years comprising 53% (n = 20) male patients. Of the initial VTE events, 74% of patients had deep vein thrombosis (DVT) or pulmonary embolism (PE), while 26% had splenic or portal vein thrombosis. About 63% (n = 24) of patients received enoxaparin and 37% (n = 14) were treated with one of the OAC (apixaban, rivaroxaban, dabigatran, or warfarin). At a mean follow-up of 6 months, rates of recurrent VTE were numerically lower but statistically non-significant in patients on OAC compared to those receiving enoxaparin (40% vs. 60%, OR 0.86 95% CI 0.12–5.8, P = 0.73). Similarly, the 1-year all-cause mortality of patients on enoxaparin was higher than patients receiving OAC (67% vs. 33%, OR 0.15, 95% CI 0.05–1.58, P = 0.3). There was no significant difference in the odds of major bleeding events (OR 0.15, 95% CI 0.01–1.71, P = 0.26) and the need for transfusions (OR 0.22, 95% CI 0.03–1.45, P = 0.24) in patients on OAC and enoxaparin. CONCLUSION: Oral anticoagulation appears to be a better alternative to enoxaparin, given its clinical feasibility and comparable safety and efficacy. Large scale studies are required to validate our findings.

P-165 - Safety and effectiveness of direct oral anticoagulants for venous thromboembolism in patients with active cancer: a retrospective study

P-165 - Safety and effectiveness of direct oral anticoagulants for venous thromboembolism in patients with active cancer: a retrospective study

Safety and efficacy of direct oral anticoagulants for venous thromboembolism and stroke prophylaxis in patients with hematologic malignancies.

Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.

Phase IIa study of dabigatran etexilate in children with venous thrombosis: pharmacokinetics, safety, and tolerability

Background The current standard-of-care treatments for pediatric venous thromboembolism (VTE) have limitations. Dabigatran etexilate (DE), a direct thrombin inhibitor, may offer an alternative therapeutic option. Objectives To assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of a DE oral liquid formulation (OLF) in pediatric patients with VTE. Patients/Methods Patients who had completed planned treatment with low molecular weight heparin or oral anticoagulants for VTE were enrolled in two age groups (2 to < 12 years and 1 to < 2 years), and received a DE OLF based on an age-adjusted and weight-adjusted nomogram. Originally, patients were to receive a DE OLF twice daily for 3 days, but the protocol was amended to a single dose on day 1. The primary endpoints were pharmacokinetics/pharmacodynamics-related: plasma concentrations of DE and its metabolites; activated partial thromboplastin time (APTT), ecarin clotting time (ECT), and dilute thrombin time (dTT); and pharmacokinetic (PK)-pharmacodynamic (PD) correlation. Safety endpoints included incidence rates of bleeding events and all other adverse events (AEs). Results Eighteen patients entered the study and received the DE OLF (an exposure equivalent to a dose of 150 mg twice daily in adults). The projected steady-state dabigatran trough concentrations were largely comparable between pediatric patients and adults. The PK/PD relationship was linear for ECT and dTT, and non-linear for APTT. No serious or severe AEs, bleeding events, or recurrent VTEs were reported. Mild AEs were reported in three patients in the single-dose group (screening period) and in one patient in the multiple-dose group (on-treatment period). Conclusion The current study supports the further evaluation of DE OLFs in pediatric patients with VTE.

Assessment of quality of life, satisfaction with anticoagulation therapy, and adherence to treatment in patients receiving long-course vitamin K antagonists or direct oral anticoagulants for venous thromboembolism.

IntroductionDirect oral anticoagulants (DOACs) have shown non-inferiority and ease of use compared to vitamin K antagonists (VKA) in the treatment of venous thromboembolism (VTE). No study so far has been directed toward real-life experience of outpatients receiving anticoagulants for VTE in France.MethodsThis is an observational descriptive real-life epidemiological study, using three validated questionnaires (Morisky Medication Adherence Scale-8, EQ-5D, and part 2 of the Perception of Anticoagulant Treatment Questionnaire), to assess adherence, quality of life, and satisfaction in 100 VTE outpatients receiving anticoagulation therapy by VKA (primary or switched from DOAC to VKA) or by DOAC (primary or switched from VKA to DOAC).ResultsPatients were very much satisfied with their treatment in both DOAC and VKA groups. Despite advantages of DOACs, therapeutic adherence was only moderate. The best adherence scores were observed in the primary VKA switched to DOAC for at least 3 months (S-DOAC) subgroup. Quality of life was better in the DOAC group mainly because of the absence of the requirement for blood testing. Most of the complaints concerned the pain/discomfort dimension in the VKA group and anxiety/depression dimension in the DOAC group.ConclusionPatients were satisfied with their anticoagulant treatment, especially when they were involved in choosing the anticoagulant, and the treatment suited them. Quality of life of patients in the DOAC group was better than in the VKA group, but adherence remains to be improved. This study highlights the importance of the physician–patient relationship, pretreatment initiation, and follow-up of any anticoagulation therapy throughout.

Patterns and Predictors of Use of Anticoagulants for the Treatment of Venous Thromboembolism Following Approval of Rivaroxaban.

Few studies have identified patterns and predictors of use of direct oral anticoagulants for venous thromboembolism (VTE). To describe the use of anticoagulants and assess predictors associated with the prescription of rivaroxaban over vitamin K antagonist (VKA) for the subsequent treatment of VTE. This cross-sectional study was built with all consecutive patients newly diagnosed with acute VTE admitted between February 18, 2013, and September 18, 2013, in an academic tertiary care center in Quebec, Canada. Patient characteristics and VTE treatments were described. Univariate analyses and a multiple forward stepwise logistic regression were performed to assess predictors of rivaroxaban use over VKA for the subsequent treatment of VTE. The study included 256 patients, 36.7% with a diagnosis of deep vein thrombosis (DVT) and 63.3% with pulmonary embolism (PE). Mean age was 63.1 years, and 28.1% of patients had cancer-associated VTE. Overall, rivaroxaban was prescribed in 1.6% of patients for the initial treatment and in nearly 20% of patients for the subsequent treatment of VTE. Low-molecular-weight heparin and VKA were mostly prescribed. Independent predictors associated with the prescription of rivaroxaban over VKA were as follows: age < 65 years (OR: 2.86, 95% CI 1.29-6.37), a diagnosis of DVT versus PE (OR 2.54, 95% CI 1.20-5.40), and an emergency department visit rather than a hospitalization (OR 2.24, 95% CI 1.06-4.71). Several months following its availability, rivaroxaban was rarely prescribed for acute VTE disease. It also appears to be prescribed in different patient populations than VKA.

Novel Oral Anticoagulants for Venous Thromboembolism with Special Emphasis on Risk of Hemorrhagic Complications and Reversal Agents.

Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes. This review summarizes the major trials that led to the approval of these agents and their exclusion criteria helping physicians understand which patient types might not benefit from these agents. It provides clinical pearls invaluable in everyday practice such as transitioning between traditional and novel anticoagulants, dose adjustments for high risk populations, drug interactions and cost analysis. Futhermore, the review provides direct comparisons with warfarin and indirect comparisons among the novel agents in terms of efficacy and bleeding risk narrating the numbers of patients with intracranial, gastrointestinal and fatal hemorrhages in each of the major trials. We hope that this review will help the physicians inform their patients about the benefits and risks of these agents and enable them to make an informed selection of the most appropriate anticoagulant.

Do women bleed more than men when prescribed novel oral anticoagulants for venous thromboembolism? A sex-based meta-analysis

Bleeding complications occur more frequently in women than men in clinical trials of warfarin and thrombolytics. It is unknown whether these sex-related differences exist for new oral anticoagulants, including dabigatran, rivaroxaban, and apixaban. To determine whether women suffer more bleeding complications with these agents, we conducted a systematic review and meta-analysis of randomized controlled trials on new oral anticoagulants for venous thromboembolism (VTE). Medline, Embase, and the Cochrane-controlled trial register on the Cochrane library were searched to identify studies that evaluated novel oral anticoagulants versus any comparator, and reported outcomes, including major bleeding and recurrent VTE, stratified by sex. No language restrictions were applied. Studies were evaluated according to a priori inclusion criteria and critically appraised using established internal validity criteria. Pooled relative risk was estimated using a random effects model. Eight studies were eligible, comprising 9417 patients. There was no difference in the primary efficacy outcome of recurrent VTE between men and women [Relative Risk (RR) 1.02, 95% confidence interval (CI) 0.74-1.39]. However, men had less major bleeding with novel oral anticoagulants compared to women [RR 0.79, 95% CI 0.66-0.97, p=0.03]. All-cause mortality was not reported by sex in any of the studies. Women suffer more bleeding complications than men when receiving novel oral anticoagulants for VTE. Future clinical trials should report outcomes stratified by sex, and further studies are needed to investigate the clinical impact of this sex-related safety difference.

Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism

The Outpatient Bleeding Risk Index (OBRI) and the Kuijer, RIETE and Kearon scores are clinical prognostic scores for bleeding in patients receiving oral anticoagulants for venous thromboembolism (VTE). We prospectively compared the performance of these scores in elderly patients with VTE. In a prospective multicenter Swiss cohort study, we studied 663 patients aged ≥ 65 years with acute VTE. The outcome was a first major bleeding at 90 days. We classified patients into three categories of bleeding risk (low, intermediate and high) according to each score and dichotomized patients as high vs. low or intermediate risk. We calculated the area under the receiver-operating characteristic (ROC) curve, positive predictive values and likelihood ratios for each score. Overall, 28 out of 663 patients (4.2%, 95% confidence interval [CI] 2.8-6.0%) had a first major bleeding within 90 days. According to different scores, the rate of major bleeding varied from 1.9% to 2.1% in low-risk, from 4.2% to 5.0% in intermediate-risk and from 3.1% to 6.6% in high-risk patients. The discriminative power of the scores was poor to moderate, with areas under the ROC curve ranging from 0.49 to 0.60 (P = 0.21). The positive predictive values and positive likelihood ratios were low and varied from 3.1% to 6.6% and from 0.72 to 1.59, respectively. In elderly patients with VTE, existing bleeding risk scores do not have sufficient accuracy and power to discriminate between patients with VTE who are at a high risk of short-term major bleeding and those who are not.