Recurrent Venous Thromboembolism Research Articles

Venous thromboembolism secondary prophylaxis in elderly people (over 75-year-old) with low-dose direct oral anticoagulants: single-center Italian experience

Nowadays, direct oral anticoagulants (DOACs) represent the gold standard for venous thromboembolism (VTE) treatment and VTE secondary prophylaxis; nevertheless, the percentage of elderly patients in major trials and literature data about DOACs usage for VTE secondary prophylaxis in the elderly are scant. Our retrospective study tried to evaluate low-dose DOACs efficacy and safety for elderly VTE secondary prophylaxis in a real-life setting. A cohort of 73 patients (≥ 75 years) considered at high risk of VTE recurrence was treated with apixaban 2.5 mg twice daily (b.i.d.) or rivaroxaban 10 mg daily as VTE secondary prophylaxis. The median low-dose DOACs administration time was 18.40 months. Three (4.1%) VTE recurrence events were observed, with four bleeding events registered (5.5%), including one major bleeding (MB) (1.4%) and two clinically relevant non major bleeding (CRNMB) (2.7%). Our data suggest that low-dose DOACs may be effective and well tolerated for secondary VTE prophylaxis in elderly patients at high risk of VTE recurrence.

Risk assessment and management strategies in older patients with acute pulmonary embolism

IntroductionManaging older patients with acute pulmonary embolism (PE) is challenging due to their underrepresentation in clinical trials, comorbidities and increased complication risk. This study evaluates risk assessment and management outcomes in older PE patients focussing on home and reperfusion treatment. MethodsA retrospective analysis was conducted on patients aged ≥70 years diagnosed with acute PE at an academic medical centre (2015-2022). Results242 patients with a mean age of 77 years were included. All 59 patients with negative Hestia criteria were discharged ≤24h, and in total 81 patients (35%) received home treatment. Among these 14-day mortality and recurrent venous-thromboembolism were 0% and major bleeding occurred in 1.3% (one patient, 95%CI 0.11-6.1). European Society of Cardiology (ESC) risk-classification showed 9 low-risk PE (3.9%), 199 intermediate-risk (87%), and 20 high-risk PE patients (8.8). In 5 of the 20 high-risk patients, hypotension was mainly caused by another condition, i.e. sepsis. Eight high-risk patients received reperfusion therapy. Fourteen-day mortality was 51% in high-risk patients (95%CI 27-71); 5 out of 8 patients receiving reperfusion treatment died within 5 days. Patients with an Acute Presenting Older Patient (APOP) score of ≥45% had higher 14-day mortality (28%; 95%CI 12-46) compared to <45% (3.2%; 95%CI 0.85-8.3; HR 10.2; 95%CI 2.6-39). ConclusionSelecting for home treatment using Hestia was safe for older PE patients in our cohort. Mortality in the high-risk group was high also when receiving reperfusion treatment. The ESC risk-classification and APOP score identified patients at higher mortality risk, suggesting their potential utility in clinical decision-making.

Outcomes in children with provoked venous thrombosis and antiphospholipid antibodies: findings from the Kids-DOTT trial

AbstractFew studies have prospectively evaluated the incidence and outcomes in children with provoked venous thromboembolism (VTE) and transient or persistent antiphospholipid antibodies (aPLs). We compared outcomes of patients aged <21 years with a first-episode acute provoked VTE and positive aPL at diagnosis, enrolled in the Multicenter Evaluation of the Duration of Therapy for Thrombosis in Children trial. aPLs were tested at enrollment and, when positive, repeated at 6 weeks after VTE diagnosis. Subsequent testing was performed at the discretion of the treating hematologist. Of 524 patients, 116 (22%) had positive aPLs at enrollment. At follow-up, 70 (60%) had transient (n = 66) or low-titer aPLs (n = 4), 11 (10%) had persistent aPLs meeting the criteria for antiphospholipid antibody syndrome (APS), and 35 (30%) had no repeat testing. Patients with APS were older (15.8 vs 9.9 years; P = .014) and had a statistically significant higher risk of symptomatic recurrent VTE (18% vs 1%; odds ratio [OR], 12.2; 95% confidence interval [CI], 1.4-108; P = .025) and a statistically nonsignificant but clinically meaningful difference in the risk of anticoagulant-related clinically relevant bleeding (9% vs 0%; OR, 20.1; 95% CI, 0.7-558; P = .077) compared with those in the transient or low-titer aPL group. In conclusion, aPLs are common in young patients with acute provoked VTE and are mostly transitory and clinically insignificant. Patients with APS and provoked VTE appear to have an increased risk of recurrent VTE compared with patients with transitory or low-titer aPLs. Future collaborative studies should investigate the optimal VTE management for children with provoked VTE who meet the criteria for APS. The trial was registered at www.ClinicalTrials.gov as #NCT00687882.

Women-specific aspects of venous thromboembolism

Women have a higher lifetime risk of venous thromboembolism (VTE) than men. Hormone-associated risk factors such as pregnancy, contraception and hormone replacement therapy contribute significantly to this. Contraception with combined hormonal contraception increases the risk of VTE in young women, with the extent of the increase in risk being determined by the level of the estrogen dose and the progestin component. After hormone associated VTE, temporary anticoagulation is sufficient in many cases, provided there are no additional persistent risk factors. Affected women should be informed that the risk of VTE recurrence is increased in a subsequent pregnancy and usually requires VTE prophylaxis with low molecular weight heparin during pregnancy. If the suspicion of recurrent VTE arises during pregnancy, diagnostics must be carried out promptly so that deep vein thrombosis and/or pulmonary embolism can be reliably confirmed or ruled out.

Impact of the VTE-PREDICT calculator on clinicians’ decision making in fictional patients with venous thromboembolism: a randomized controlled trial

BackgroundAfter 3 months of anticoagulation for venous thromboembolism (VTE), the decision needs to be made whether to stop anticoagulation or extend treatment indefinitely. The VTE-PREDICT calculator can be used to estimate individual risks of VTE recurrence and bleeding to guide this decision. ObjectivesTo evaluate the impact of predicted individual risks of recurrence and bleeding on clinicians’ decisions on anticoagulation duration and to assess usefulness of the VTE-PREDICT calculator. MethodsA randomized controlled trial and within-subject study was conducted among clinicians treating VTE patients. The clinicians were asked to complete an online survey containing 6 fictional case vignettes. Group A proposed anticoagulant duration for each case without additional information first and subsequently after seeing calculator-predicted risks (within-subject analysis). Group B was directly provided with calculator risks and proposed treatment duration for each case vignette (for comparison with group A results in a randomized controlled trial analysis). Then, group B received questions on usefulness and credibility of the calculator. ResultsForty-five clinicians were assigned to group A and 48 to B. Overall, group A did not propose different anticoagulation durations than group B. However, individual clinicians in group A changed proposed duration in 35% of the cases after seeing the calculator risks. The calculator was considered useful and credible by most clinicians. ConclusionOverall, use of the VTE-PREDICT calculator did not affect proposed anticoagulation duration. However, individual clinicians frequently changed their proposed duration after using the calculator, especially for patients with high bleeding risk.

Safety and Effectiveness of Direct Oral Anticoagulants Versus Warfarin in Patients with Venous Thromboembolism using Real-World Data: A Systematic Review and Meta-Analysis.

Direct oral anticoagulants (DOACs) have shown comparable efficacy and a superior safety profile in clinical trials for patients with venous thromboembolism (VTE). However, further study is needed to assess DOACs' effectiveness and safety compared to warfarin in a real-world context. Thus, this meta-analysis compares the effectiveness and safety of warfarin and DOACs in patients with VTE. A systematic review of the literature using PubMed and EMBASE was conducted from inception until June 2024. We examined observational studies that compared safety and effectiveness between DOACs and warfarin when used in treating VTE and reported adjusted hazard ratios (HRs) and/or odds ratios (ORs) for recurrent VTE, major bleeding, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and death from any cause. We then estimated the pooled effect using the random-effects model for meta-analysis. A total of 25 studies were included in the current meta-analysis. DOAC therapy was associated with significantly lower risks of recurrent VTE (HR 0.76, 95% confidence interval [CI] 0.69-0.85), major bleeding (HR 0.77, 95% CI 0.72-0.83), clinically relevant non-major bleeding (HR 0.82, 95% CI 0.77-0.88), and gastrointestinal bleeding (HR 0.75, 95% CI 0.68-0.83) compared to warfarin. However, no statistically significant difference was observed in all-cause mortality between the two groups (HR 0.96, 95% CI 0.83-1.10). This meta-analysis found that DOACs are associated with a significant reduction in VTE recurrence in addition to the known favorable safety profile when compared to warfarin.

AN UPDATE ON DIAGNOSIS AND MANAGEMENT OF THROMBOEMBOLISM IN PREGNANCY

Thromboembolism during pregnancy poses a significant challenge in maternal healthcare, substantially contributing to maternal morbidity and mortality worldwide. Understanding its diagnosis and management is crucial for improving maternal and fetal outcomes. Objective: To evaluate the diagnosis and management of thromboembolism in pregnant women. Methods: A retrospective cohort study was conducted at Lady Reading Hospital, Peshawar, from July 2022 to July 2024. The study included 175 pregnant females diagnosed with venous thromboembolism (VTE) during their pregnancy. Data were collected on patient demographics, trimester of diagnosis, type of thromboembolism (deep vein thrombosis [DVT] or pulmonary embolism [PE]), treatment modalities, and outcomes. Patients were treated with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH). Descriptive statistics were used to analyze the data, with results presented as percentages and means with standard deviations. Results: The mean age of the participants was 32.01 ± 2.35 years. Thromboembolism was most commonly diagnosed in the third trimester (65%), followed by the second trimester (25%) and the first trimester (10%). DVT was observed in 74% of patients, while PE occurred in 26%. Among the 160 patients treated with LMWH, 3% (5 patients) experienced a recurrence of VTE. Of the 15 patients who received UFH, 5% (8 patients) had significant bleeding complications. Overall maternal outcomes included a 3% recurrence rate of VTE and a 5% rate of significant bleeding complications. No maternal mortality was reported. Conclusion: Early diagnosis and timely management of thromboembolism in pregnancy, mainly through the use of low molecular weight heparin and a multidisciplinary care approach, significantly improve maternal and fetal outcomes. LMWH was associated with fewer complications compared to UFH, highlighting its effectiveness and safety in treating pregnant women with VTE.

Baseline platelet count and long-term clinical outcomes in patients with acute venous thromboembolism: a prospective cohort study.

An abnormal platelet count (PC) is common in acute venous thromboembolism (VTE) but its relationship with clinical outcomes remains ill-defined. We aimed to explore the association between baseline PC and the long-term risk of clinically relevant outcomes in a prospective cohort of 991 patients with acute VTE. We classified patients into four PC groups: very low (< 100 G/l), low (≥ 100 to < 150 G/l), normal (≥ 150 G/l to ≤ 450 G/l), and high (> 450 G/l). The primary outcome was major bleeding (MB), secondary outcomes were recurrent VTE and overall mortality. We examined the association between PC and clinical outcomes, adjusting for confounders, competing risk for mortality, and periods of anticoagulation. After a median follow-up of 30 months, 132 (13%) of patients experienced MB, 122 (12%) had recurrent VTE, and 206 (21%) died. Compared to patients with a normal PC, patients with a very low PC had a sub-distribution hazard ratio (SHR) for MB of 1.23 (95% confidence interval [CI] 0.52-2.91) and those with a high PC a SHR of 1.87 (95%CI 0.82-4.29). Patients with a low PC had a twofold increased VTE recurrence risk (SHR 2.05, 95%CI 1.28-3.28). Patients with low and very low PC had a hazard ratio for mortality of 1.43 (95%CI 0.99-2.08) and of 1.55 (95%CI 0.80-2.99), respectively. Our findings do not suggest a consistent relationship between baseline PC and long-term clinical outcomes in patients with VTE.

Utility of the modified Ottawa score for identification of more preferable candidates of extended anticoagulation therapy in cancer-associated isolated distal deep vein thrombosis: insight from the ONCO DVT Study

BackgroundThe ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups. ObjectivesTo identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score. MethodsIn this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤−1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups. ResultsThe cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism–related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups. ConclusionA 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score.

The Efficacy and Safety of DOACs in Inherited Antithrombin Deficiency: A Cohort Study from a Tertiary Referral Center.

Individuals with inherited antithrombin deficiency (IATD) have a high risk of venous thromboembolism (VTE). Most VTEs are managed with direct oral anticoagulants (DOACs), but the utility of DOACs in antithrombin deficiency (ATD) is unreported. Patients with IATD treated with DOAC were identified from our institutions' IATD registry. We assessed patients' characteristics, ATD type, and initial VTE characteristics, thrombosis recurrence and bleeding rates. Thirty-three patients received DOACs for 73 (38.5-111.5) months (median (interquartile range)). Prior to taking DOACs, 12 (36%) patients had VTE recurrence: these occurred after anticoagulation was ceased (4), nonadherence to VKA prior to DOAC use (3), or during heparin use in pregnancy (5). There were no VTE recurrences on standard-dose DOAC, except in a noncompliant patient receiving dabigatran. There was one recurrence with compliant DOAC use-a patient receiving rivaroxaban 10 mg. Six (18%) patients experienced clinically relevant bleeding, which was predominantly menorrhagia (5/6). One major bleeding event, intracranial hemorrhage, occurred in a patient receiving full-dose rivaroxaban who had refractory hypertension (0.5 events/100 patient-years). In this cohort, compliant DOAC users had an overall VTE recurrence rate of 0.5/100 patient-years, whereas with low-dose DOACs the event rate was 3.5/100 patient-years. Standard-dose DOACs appear efficacious and relatively safe in IATD.

Recurrent venous thromboembolism and vaginal estradiol in women with prior venous thromboembolism: A nested case-control study.

Whether vaginal estradiol use is associated with an increased risk of recurrent venous thromboembolism (VTE) in women with prior VTE is unknown. We sought to evaluate the association between vaginal estradiol use and recurrent VTE in women with prior VTE. We performed a nationwide nested case-control study among 44 024 women aged ≥45 years who developed a first VTE without a history of vaginal estrogen use prior to VTE diagnosis. Cases with recurrent VTE were matched 1:2 on birth year with controls using incidence density sampling. Exposure to vaginal estradiol tablets was categorized into current use (0-2 months before index), prior use (2-24 months before index) and past use (more than 24 months prior to index). We identified 5066 cases and 10 127 age-matched controls. In fully adjusted analysis vaginal estrogen was not associated with recurrent VTE with a hazard ratio of 0.75, p = .07 for current use, 0.83, p = .13 for prior use, and 1.24, p = .06 for past use. Use of vaginal estradiol tablets in women with prior VTE was not associated with an increased rate of recurrent VTE. Our study indicates that vaginal estradiol therapy is unlikely to increase risk of recurrent VTE in women with prior VTE.

Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism.

Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH. Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: insight from the COMMAND VTE Registry-2.

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era.

Selective iliofemoral stent placement for complex pediatric cases: a decade of institutional experience.

Pediatric iliofemoral venous thromboembolism that is resistant to conventional treatments poses significant management challenges. Stent placement represents a potentially underutilized strategy in children when stenosis or thrombosis persists intraprocedurally or recurs postoperatively, despite treatments such as venoplasty, lysis, and thrombectomy. This study aims to report our institutional experience with iliofemoral stenting in 17 pediatric patients with recurrent iliofemoral venous thromboembolism or stenosis. We performed an IRB-approved retrospective review of pediatric patients (<18 years of age) who underwent iliofemoral venous stenting for recurrent stenosis or thrombosis between January 2012 and December 2022 at a single tertiary care institution. Patient demographics, risk factors for venous thromboembolism, presenting symptoms, and procedural characteristics were recorded. The primary outcome was stent patency rates at interval imaging follow-up. Seventeen patients with mean age of 14.6 years (range 7-17) and mean BMI of 27.7 were stented during the study period. Sixteen of 17 patients presented with evidence of May-Thurner anatomy. 14/17 patients presented with acute iliofemoral venous thromboembolism, 2/17 with chronic venous thromboembolism, and 1/17 with left lower extremity swelling without thrombosis. Seventy-three total angiographic procedures were performed, which included angioplasty, lysis, and thrombectomy, and 23 stent placements. Patients underwent an average of 3 procedures (range 1-9) over a mean of 2.8 months (range 0-17 months) prior to undergoing stent placement. Stents were deployed successfully in all patients. The median follow-up was 18 months (range, 1-77 months). Primary and secondary patency rates were 13/17 (76%) and 14/14 (100%) at 12 months and 12/17 (71%) and 14/14 (100%) at 24 months, respectively. In our experience of 17 patients, stent placement appears to be a durable option for children with iliofemoral venous thromboembolism following failure to establish vessel patency or development of recurrent thrombosis/stenosis postoperatively.

Direct Oral Anticoagulants: Probability of Recurrent Venous Thromboembolism and Bleeding Risk in an Obese Population.

Direct-acting oral anticoagulants (DOACs) have become the preferred drugs for managing venous thromboembolism (VTE). Despite their advantages over vitamin K antagonists such as warfarin, their use in obese patients remains controversial with many providers reluctant to switch patients managed on warfarin. Outcome research that opts to increase provider confidence when prescribing DOACs for patients with obesity will be invaluable. This investigation evaluated whether patients with a body mass index (BMI) 35 kg/m2 or greater who were prescribed a DOAC had a higher risk for a recurrent VTE or bleed event relative to warfarin. The study was conducted in West Virginia which has the highest rate of obesity in the United States. Of the total study population (1633), 2.3% (37) had a recurrent thrombotic event, 5.5% (89) had a major bleed event, and 10.7% (174) had some type of bleeding event. No individual patient characteristic was associated with recurrent thrombosis-including BMI. Older age, antiplatelet use, and taking a medication with a theoretical risk of increasing the effect of DOACs were associated with any and major bleeding events. The use of warfarin was associated with major bleeding events more frequently versus a DOAC. Body mass index was not a predictor for recurrent VTE or any bleed or major bleed events. These findings support the conclusion that DOACs are an appropriate and effective drug class for the management of VTE in patients with obesity.

Temporal Changes in Long-Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era.

There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long-term outcomes from the warfarin era to the DOAC era. We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010-2014) and Registry 2: 5197 patients in the DOAC era (2015-2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P<0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P=0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P=0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P=0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P=0.63). Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.

Statins during Anticoagulation for Emergency Life-Threatening Venous Thromboembolism: A Review.

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors-the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

The use of non-vitamin K antagonist oral anticoagulants in chronic thromboembolic pulmonary hypertension: an updated meta-analysis.

Studies have demonstrated the beneficial effects of non-vitamin K antagonist oral anticoagulants (NOACs) for the treatment of atrial fibrillation and venous thromboembolism (VTE). The impact of NOACs on chronic thromboembolic pulmonary hypertension (CTEPH) remains controversial. This meta-analysis was conducted to investigate the effectiveness and safety of NOACs compared with vitamin K antagonists (VKAs) in patients with CTEPH. A comprehensive search of PubMed, Embase, and Cochrane Library was conducted for relevant studies, encompassing data from inception until November 2023. The data were pooled using a fixed-effects model if the I2 value was less than 50%; otherwise, a random-effects model was employed. Overall, two randomized controlled trials (RCTs) and eight observational studies involving 4556 patients with CTEPH were included. Patients receiving NOACs exhibited a significantly lower incidence of all-cause mortality (odds ratio [OR] = 0.52, 95% confidence interval [CI]: 0.36-0.76) and major bleeding (OR = 0.58, 95% CI: 0.36-0.92) compared to those with VKAs. There were no significant differences in the rate of VTE recurrence (OR = 1.07, 95% CI: 0.72-1.59), total bleeding (OR = 0.78, 95% CI: 0.60-1.01), and minor bleeding (OR = 1.11, 95% CI: 0.73-1.69) between the two studied groups. Similar results were found in the subgroup analysis and sensitivity analysis.This meta-analysis provided evidence that NOACs could be superior to VKAs for the treatment of CTEPH. NOACs might be safe and a convenient alternative to VKAs for thromboprophylaxis in patients with CTEPH.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Direct oral anticoagulants versus low-molecular-weight heparin in patients with cancer-associated venous thrombosis: a cost-effectiveness analysis.

Direct oral anticoagulants (DOACs) have demonstrated clinical benefits and better patient adherence over low-molecular-weight heparin (LMWH) in treating patients with cancer-associated venous thrombosis (CAT). We aimed to compare the cost-effectiveness of DOACs against LMWH in patients with CAT from the perspective of the Hong Kong healthcare system. A Markov state-transition model was performed to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) for DOACs and LMWH in a hypothetical cohort of 10,000 patients with CAT over a 5-year lifetime horizon. The model was primarily based on the health states of no event, recurrent venous thromboembolism, bleeding, and death. Transition probabilities, relative risks, and utilities were derived from the literature. Resource cost data were obtained from the Hong Kong Hospital Authority. Deterministic and probabilistic sensitivity analyses tested the robustness of the results. Relative to LMWH, DOACs were associated with increased QALYs (1.52 versus 1.50) at a lower medical cost of USD 2,232 versus 8,224 in five years. The cost of LMWH was the main contributor to the outcome. Out of 10,000 simulated cases, DOACs were dominant in 15.8% and cost-effective in 42.1%, at the willingness-to-pay threshold of USD 148,392 per additional QALY. DOACs were associated with greater QALY improvements and lower overall costs compared to LMWH. Accounting for uncertainty, DOACs were between cost-effective and dominant in 57.9% of cases. DOACs are a cost-effective alternative to LMWH in the management of CAT in Hong Kong.