Months Of Anticoagulant Therapy Research Articles

Effect of direct oral anticoagulants compared to enoxaparin on objective response to immune checkpoint inhibitors in patients with lung cancer.

A hypoxic tumor microenvironment inhibits the normal functioning of immune cells. Studies have hypothesized that anticoagulants that can penetrate and bind to factor Xa in the tumor microenvironment, can enhance T-cell function and augment immunotherapy activity. This study compared objective response rate and progression-free survival of lung cancer patients on concomitant immunotherapy treated with direct-acting oral anticoagulants versus enoxaparin. This single-center retrospective study included 73 adults with stage-IV lung cancer who received at least two cycles of immunotherapy and one month of anticoagulant therapy with direct-acting oral anticoagulants (Arm A) versus enoxaparin (Arm B) between June 1, 2016, to September 30, 2022. Primary endpoint was objective response rate, and secondary endpoints were rates of complete response, progression-free survival, incidence of thrombotic events, and major bleeding. Objective response rate at 6 months was 24.5% versus 25% while progression-free survival at 6 months was 54.7% versus 45% in Arm A versus Arm B, respectively. Complete response rates at 6 months were 7.5% in Arm A versus 0% in Arm B. One patient in Arm A and two in Arm B had a recurrent deep vein thrombosis. Nine patients in Arm A and two in Arm B were diagnosed with new deep vein thrombosis. One patient in Arm B was diagnosed with new pulmonary embolism. Two major bleeding events occurred in Arm B. Our study suggests a trend toward improved progression-free survival at 6 months with no new safety concerns in lung cancer patients on concurrent immunotherapy and direct-acting oral anticoagulants.

Living-donor lobar lung transplantation for pulmonary Langerhans cell histiocytosis complicated by extensive thrombi in central pulmonary arteries

BackgroundPulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery.Case presentationA 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis.ConclusionPreoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study

The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Sanofi and Rovi, Sanofi Spain.

Optimizing Venous Stenting: Consensus Recommendations for Enhanced Management of Lower Extremity Deep Vein Thrombosis.

Deep vein thrombosis (DVT) poses a complex challenge and often leads to postthrombotic syndrome (PTS), a debilitating complication. The emergence of venous stents offers a potential preventive avenue against this complication. This study aimed to provide consensus recommendations on the use of venous stent for DVT. From June to July 2023, 20 internal medicine, angiology and vascular surgery, and vascular and interventional radiology experts were involved in the Delphi process. Thirty-one recommendations, categorized into three thematic areas, were rigorously evaluated: indications for stent use, stent selection and placement, and monitoring and prevention of complications. Agreement was evaluated using a Likert scale, with consensus defined as agreement by two-thirds of the participants. Consensus was reached for 23 (74.2%) of 31 recommendations. The agreement was centered on considerations, such as stent placement in specific acute DVT scenarios, emphasizing pivotal stent characteristics. However, there were divergences in the recommended stent length to prevent migration and stent characteristics based on iliocaval bifurcation morphology. Notably, there was no consensus on whether patients with DVT caused by a major transient risk factor need more than 3 months of anticoagulation therapy or whether aspirin should be added to anticoagulant treatment after venous stenting. These consensus recommendations offer practical insights into optimizing venous stent use to prevent PTS in DVT patients. Addressing the critical aspects of stent selection, placement, and postprocedural care, these recommendations contribute to clinical decision-making. The identified divergences underscore the importance of consensus and thus indicate the need for further investigation.

Extending venous thromboembolism secondary prevention with apixaban in cancer patients. The EVE trial

BackgroundCancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. ObjectivesThe study’s purpose was to determine whether this dose reduction is advisable for cancer-associated VTE. MethodsA randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding. ResultsOf 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67). ConclusionFor secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883).

Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial

IntroductionPatients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an...

Left atrial appendage thrombus with severe mitral stenosis: Responders and non-responders to anticoagulation

Introduction and ObjectiveMitral stenosis (MS) is one of the most frequently observed valvular heart lesions in developing countries and is due to different etiologies. The effects of anticoagulation in different types of left atrial appendage (LAA) are unknown. The current study aimed to determine the resolution of LAA thrombus on transesophageal echocardiography (TEE) after three months of optimal anticoagulation in patients with different types of LAA at baseline cardiac computed tomography of patients with severe MS. MethodsThis prospective cohort study observed the frequency of LAA thrombus resolution after three months of anticoagulation therapy in patients with severe MS. The response rate in different morphologies of LAA and locations was also assessed. Thrombus resolution after three months of warfarin therapy was assessed on repeat TEE. ResultsA total of 88 patients were included, mean age 37.95±11.87 years. Repeat TEE showed thrombus resolution in only 27.3% of patients. The rate of thrombus resolution was 8/12 (66.7%), 4/28 (14.3%), 8/36 (22.2%), and 4/12 (33.3%) for patients with cactus, cauliflower, chicken wing, and windsock LAA type, respectively. The resolution rate was 0/12 (0%), 4/44 (9.1%), and 20/32 (62.5%) for patients with thrombus in the base, body, and tip of the LAA, respectively. ConclusionThe cactus type of LAA morphology and thrombus at the LAA tip responded well to three months of anticoagulation, however, patients with thrombus in the LAA base and body and cauliflower and chicken wing morphology were non-responders and could benefit from early referral for surgical management.

Assessing the Feasibility of Thromboprophylaxis with Apixaban in JAK2-Positive Myeloproliferative Neoplasm Patients: The Airport-MPN Trial

Introduction: Thrombosis is a major cause of mortality and morbidity in myeloproliferative neoplasms (MPN). In patients classified as high-risk for thrombosis, current guidelines recommend the use of cytoreduction therapy and low-dose aspirin (e.g., ASA 81 mg daily) to decrease the risk of thrombotic events. However, use of low-dose aspirin is based on limited evidence and is associated with a significant failure rate. Thromboprophylaxis with low-dose direct oral anticoagulants (e.g., apixaban 2.5 mg BID) is an appealing option in MPN, specifically when patients carry the JAK2 mutation, based on the pathophysiology of thrombus formation associated with this driver mutation. In other populations, thromboprophylaxis with a low-dose direct oral anticoagulant has been associated with a reduced risk of arterial and venous thrombotic complications, when compared to low-dose aspirin. Hence, we conducted a pilot trial to assess the feasibility of conducting a randomized controlled trial evaluating the efficacy and safety of apixaban (2.5 mg BID) compared to aspirin (81 mg daily) to prevent thrombotic complications in patients with JAK2-positive MPN (JAK2MPN). Methods: This was a multi-centre, prospective, open-label, blinded endpoint pilot trial (NCT04243122), conducted in three Canadian centers (Ottawa, Calgary, Sherbrooke). Adult patients with a confirmed diagnosis of polycythemia vera, JAK2-positive essential thrombocythemia or JAK2-positive pre-fibrotic myelofibrosis (per local clinical definitions) requiring low-dose aspirin for thromboprophylaxis were eligible. Both patients with an incident diagnosis of JAK2MPN (defined as diagnosed within 1 year) and patients with prevalent disease were targeted for recruitment. Exclusion criteria included a contraindication to thromboprophylaxis or the need for a specific anticoagulant or non-aspirin anti-platelet agent. Patients with a prior history of venous thromboembolism were eligible if they had completed a minimum of 6 months of anticoagulation therapy. Participants were randomized 1:1 to receive apixaban 2.5mg BID or aspirin 81mg daily, along with cytoreductive therapy (per guidelines). The study treatment duration was 6 months. Follow-up occurred at 3, 6 and 7 months after allocation of the study medication. The primary study outcome for feasibility was the monthly recruitment rate per study site over a 6-month follow-up period. Secondary outcomes included rates of thrombotic and bleeding complications. The total estimated sample size was 44 participants (22 per arm). Due to the COVID-19 pandemic, not all sites were able to start recruitment at the same time and the total recruitment period spanned over 24 months. Results: During this 24-month recruitment period, 93 JAK2MPN patients were screened for eligibility. Of these, 69 were eligible and 64% of eligible patients consented to participate. We therefore recruited 44 participants, for a recruitment rate of 0.8 patient per centre per month. Baseline characteristics of participants are presented in Table 1. A total of 29 prevalent cases and 15 incident cases were included. Secondary efficacy, safety, and feasibility outcomes (relating to thrombotic events, bleeding complications, and study compliance) will be available at the ASH Meeting, since all participants will have completed the 6-month treatment duration by October 2023. Discussion: Despite the challenges of the COVID-19 pandemic, we have recruited 100% of our target population. Given the chronicity of MPN, most outpatient clinics functioned remotely during the pandemic, precluding recruitment. Nevertheless, by adapting to the realities of the pandemic, we achieved our recruitment target demonstrating feasibility of a larger trial. The strategies adopted during this pilot trial to recruit participants, such as active screening of clinic lists for potential participants and direct communication with MPN specialists, will be applied to our larger scale trial. Conclusion: This pilot trial demonstrated the feasibility of conducting a large-scale trial evaluating the superiority of apixaban over aspirin for the thromboprophylaxis of JAK2MPN patients. As JAK2MPN are rare diseases, we have partnered with counterparts in France to conduct an international study on the efficacy and safety of direct oral anticoagulant thromboprophylaxis in JAK2MPN patients.

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis

The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Erasmus MC.

Safety and Efficacy of Transjugular Intrahepatic Portosystemic Shunt for Non-tumoral Cirrhotic Portal Vein Thrombosis Not Responding to Anticoagulation Therapy.

To evaluate the feasibility, safety, and efficacy of add-on transjugular-intrahepatic-portosystemic shunt (TIPS) for portal vein recanalization (PVR) in cirrhotic patients with non-tumoral chronic portal vein thrombosis (PVT) after 6months of monitored anticoagulation therapy (ACT). We conducted a retrospective search of the hospital database for patients who underwent TIPS for persistent PVT despite 6months of ACT (January 2011 to August 2021). These patients were compared to control group (ACT group; no TIPS but continued on ACT). Post-TIPS periodic assessment was done to look for clinical outcome, PVR (using contrast-enhanced CT scan), and complications. A total of 90 patients were analyzed. Thirty-six patients in TIPS group and 54 patients in ACT group. TIPS was successfully performed in all patients. TIPS group showed complete recanalization of portal vein in 77.8%, partial recanalization in 16.7%, and stable thrombus in 5.5% of the patients. TIPS thrombosis was seen in 3 patients, all underwent successful endovascular thrombolysis. Seven patients developed post-TIPS hepatic encephalopathy and were managed conservatively. In contrast, no patient in ACT group achieved PVR on 12-month follow-up. After propensity score matching, patients in TIPS group showed significantly lower incidence of variceal re-bleeding (22.2% vs. 77.8%, p = 0.03) and refractory ascites (11.1% vs. 51.9%, p < 0.01) with significantly better 12-month survival as compared to ACT group (88.9% vs. 69.4%, p = 0.04). TIPS in cirrhotic patients with PVT result in superior recanalization rates, better control of ascites, and variceal re-bleeding resulting in better survival. TIPS may be considered a preferred therapy after anticoagulation failure. TIPS is associated with good technical and clinical success in patients of cirrhosis with PVT and should be considered in patients not responding to ACT.

Right ventricular function assessment by 3D echocardiography and 2D speckle-tracking imaging in acute pulmonary embolism

Objective: To assess changes in right ventricular (RV) function parameters determined by three-dimensional (3D) echocardiography and two-dimensional (2D) speckle-tracking echocardiography in patients with acute pulmonary embolism without systemic hypotension, as compare to a control population. Subject and method: Fifty-seven intermediate-high risk pulmonary embolism patients were prospectively studied at the onset of the acute episode and after median follow-up periods of 30 days. A control group of age-and sex-matched subjects were selected. All patients and the controls underwent 2D and 3D transthoracic echocardiography within 24 hours of pulmonary embolism diagnosis and one month after hospital discharge. Tricuspid annular peak systolic velocity (s’), tricuspid annular plane systolic excursion (TAPSE), RV diameter, RV fractional area change (FAC), 3D RV ejection fraction (EF), 2D RV global strain and RV free wall strain were measured. Result: From Dec. 2019 to March 2022, fifty-seven patients with acute intermediate-high risk of early mortality PE were included. Mean age was 56 ± 14 years. Men accounted for 47.4% (27/57). Control group consisted of 34 subjects. Pulmonary embolism patients initially had RV dysfunction as assessed by 2D and 3D parameters: RV diameter: 29.3 ± 4.6mm; TAPSE: 14.6 (9.1-15.7) mm; FAC: 31.5 (30.5-39.9)%; 3DRVEFL 31.9 ± 7.7%; RVGS: -9.8 ± 3%, RVFWS: -8.9 ± 3.3%. At 30-day follow-up: s’, TAPSE, RV diameter, RV FAC were restored compared to the control group, systolic pulmonary artery pressures decreased significantly, right atrial pressure, also decreased significantly at follow-up, contrary to 3DRVEF and RV 2D global strain and free wall strain. Conclusion: After 1 month of anticoagulant therapy in patients with intermediate-high risk pulmonary embolism, RV function has not fully recovered as assessed by 3D RVEF and 2D strain imaging, while the traditional echocardiographic assessment could not detect this incomplete recovery. Further studies are needed to assess the prognostic role and implications of this residual 3DRVEF and 2D RV strain impairment after PE.

Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism: a systematic review and meta-analysis of individual participant data

We aimed to assess the relationship between residual pulmonary vascular obstruction (RPVO) on planar lung scan after completion of at least 3 months of anticoagulant therapy for acute pulmonary embolism (PE) and the risk of recurrent venous thromboembolism (VTE) or death due to PE one year after treatment discontinuation. The systematic review was registered with the International Prospective Registry of Systematic Reviews (PROSPERO: CRD42017081080). The primary outcome measure was to generate a pooled estimate of the rate of recurrent VTE at one year in patient with RPVO diagnosed on planar lung scan after discontinuation of at least 3 months of anticoagulant treatment for an acute PE. Individual data were obtained for 809 patients. RPVO (ie, obstruction >0%) was found in 407 patients (50.3%) after a median of 6.6 months of anticoagulant therapy for a first acute PE. Recurrent VTE or death due to PE occurred in 114 patients (14.1%), for an annual risk of 6.4% (95% confidence interval, 4.7%-8.6%). Out of the 114 recurrent events, 63 occurred within one year after discontinuation of anticoagulant therapy corresponding to a risk of 8.1% (6.4%-9.8%) at 1 year. The risk of recurrent VTE at one year was 5.8% (4.4-7.2) in participants with RPVO <5%, vs 11.7% (9.5-13.8) in participants with RPVO ≥5%. RPVO is a significant predictor of the risk of recurrent venous thromboembolism. However, the risk of recurrent events remains too high in patients without residual perfusion defect for it to be used as a stand-alone test to decide on anticoagulation discontinuation.

Risk of recurrent cancer-associated thrombosis after discontinuation of anticoagulant therapy

BackgroundClinical guidelines suggest continuing anticoagulation therapy for >6 months for patients with active cancer and venous thromboembolism (VTE). However, data regarding the safety of its discontinuation are scarce. ObjectivesTo valuate the risk factors and the incidence of recurrent VTE 6 months after the discontinuation of anticoagulation therapy in patients with cancer-associated thrombosis (CAT). MethodsWe performed a retrospective study on consecutive patients with CAT recruited between 2008 and 2019. The primary and secondary outcomes were recurrent VTE at 6 and 12 months, respectively. Sensitivity analyses were conducted to investigate the possible heterogeneity of these effects. ResultsA total of 311 patients were included, among whom 33.4% had metastases and 30.8% were still receiving oncological treatment after 6 months of anticoagulant therapy. At 6 and 12 months, the incidences of recurrent VTE were 6.1% (95% CI, 3.5–9.4%) and 8.7% (95% CI, 5.8–12.4%), respectively. Recurrent VTE was more frequent in patients with metastases at 6 (sub-distribution hazard ratio [SHR] 3.83; 95% CI, 1.54–9.52) and 12 months (SHR 5; 95% CI, 2.2–11.5). Patients with incidental VTE had fewer recurrent events at 6 (SHR 0.3; 95% CI, 0.1–0.8) and 12 months (SHR 0.3; 95% CI, 0.1–0.6) after discontinuing the anticoagulant therapy. ConclusionThe incidence of recurrent VTE at 6 and 12 months following the discontinuation of anticoagulant therapy is higher in patients with CAT. Patients with metastases were at an increased risk of recurrent VTE, whereas patients with incidental VTE were at a lower risk.

Available Risk Scores Modestly Predict Hemorrhage in Patients with Atrial Fibrillation and Cance

Background: Patients with cancer have an increased risk of developing atrial fibrillation (AF). Patients with cancer who develop AF have an increased risk of cardiovascular-related death at 12-months. Use of anticoagulant therapy may benefit these patients. However, patients with cancer are at increased risk of anticoagulant-related bleeding. Several risk prediction models are available to estimate the risk of anticoagulant-related bleeding in patients with AF. However, these models were developed predominately in patients without cancer. Thus, the utility of these models in cancer is unknown. We aimed to evaluate the performance of existing bleeding risk models in a cohort of patients with active cancer and AF starting on anticoagulant therapy. Methods: Using a nationwide cohort of US Veterans, we identified patients with active cancer and AF with a new prescription for anticoagulant therapy between 2012 and 2018. Cancer was defined as active if the diagnosis of AF occurred within 3 months prior to up to 6 months after new cancer diagnosis or in the setting of incurable hematological cancers (e.g., multiple myeloma, chronic myelogenous leukemia) or metastatic solid tumors. We identified anticoagulant-related major bleeding (MB) within 6 months of anticoagulant start by the presence of inpatient ICD-9/10 codes in any position as previously validated. Patients were censored 30-days after last anticoagulant prescription. We evaluated the predictive performance of six models. The association per standard deviation increase in the score and MB within 6 months of anticoagulant start was estimated using Fine-Gray subdistribution survival analysis to account for the competing risk of death≥÷A sensitivity analysis limiting inpatient ICD-9/10 codes for MB to the first two positions was also performed. We evaluated model discrimination using Harrell's c-statistic. Results: 5716 patients met inclusion criteria into the cohort. The most common types of cancer included: hematological malignancies (24%), lung (20%), prostate (18%), non-prostate genitourinary (11%), and gastrointestinal (10%) cancer. Mean age at the start of anticoagulant therapy was 73.4 years and median overall survival 41.1 months. Of the cohort, anticoagulant therapy was as follows: 2040 warfarin, 179 LMWH, 5 fondaparinux, and 3495 DOAC. 328 (5.7%) patients had a MB within 6 months of anticoagulant start and 439 (7.7%) within 12 months. The most common type of bleeds within the first 6 months of anticoagulant therapy was gastrointestinal (47%), followed by hematuria (28%) and hemoptysis (13.7%). 2.4% of bleeding events (n=8) were intracranial hemorrhage. The increase in hazard of bleeding per each standard deviation increase in bleeding score is in Table 1. For model discrimination, Harrell's c-statistic for each score is also listed in Table 1. Conclusions: In this cohort of 5716 patients with active cancer and atrial fibrillation starting on anticoagulant therapy, available clinical risk models moderately predicted bleeding. The addition of cancer-specific risk factors might improve accuracy of the available models. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non‐pregnant adults

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non‐pregnant adults

Clinical epidemiology of venous thromboembolic disease: An institutional registry.

IntroductionVenous thromboembolism (VTE) is a major health concern, with an annual incidence of ~1 in 1,000. The epidemiology of VTE in Saudi Arabia has not been adequately described yet. Therefore, this study aimed to assess the clinical characteristics, risk factors, diagnostic methods, management, and clinical outcomes of patients with VTE.MethodsThis study was based on a VTE registry created over ten years at King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. All adult inpatients and outpatients referred to the thrombosis unit of the KFMC with clinically suspected VTE including pulmonary embolism (PE) and deep vein thrombosis (DVT) were enrolled. Data were collected using a standardized case report form, which included demographic and clinical characteristics, risk factors, diagnostic methods, management, and outcomes.ResultsA total of 1,008 patients were recruited. Most patients were women (73.2%), and more than half of all patients had unprovoked VTE (58%). Among the provoked cases, the most frequent cause was surgery (29.8%), followed by hospitalization (24.2%). There was a significant statistical association between provoked status and sex, family history of VTE, smoking, recent hospitalization within 3 months for a medical condition, the site of VTE, and underlying peripheral vascular disease and varicose veins (all p < 0.05). The majority (88.3%) of patients with deep vein thrombosis was hospitalized for ≤3 days (n = 433, 79.9%), while fewer than half of the patients with PE needed hospitalization (45.3%). Thrombolytic therapy was administered to 14.1% (n = 142) of patients, and catheter-directed thrombolysis was performed in 1.0% (n = 10) of patients. The odds of mortality for provoked VTE were 3.20 times higher than those of unprovoked VTE [2.12–4.83; p-value < 0.001].ConclusionUnprovoked VTE was more common than provoked VTE in the Saudi Arabian cohort, implying hereditary predisposition. Furthermore, male sex, family history of VTE, prior history of VTE, type of VTE, underlying obesity, history of trauma, surgery, hospitalization, pregnancy, and 3–6 months of anticoagulation therapy were the most critical risk factors for VTE recurrence. The treatment patterns and clinical results were comparable to those reported in the literature.

Investigation of the ongoing pulmonary defects with perfusion-single photon emission computed tomography/computed tomography in patients under anticoagulant therapy for coronavirus disease 2019-induced pulmonary embolism.

It was aimed to reveal the continuing perfusion defect rates in patients with a diagnosis of pulmonary embolism (PE) due to COVID-19 who have completed the third month of anticoagulant therapy but whose symptoms or laboratory elevations continue. Patients with COVID-19 who were diagnosed with PE by Q-SPECT-CT between 1 September 2020 and 1 November 2021, who underwent control Q-SPECT/CT were included in the study. Demographic characteristics, laboratory findings, and first and second Q-SPECT/CT evaluation results of the patients were recorded. It was observed that the pulmonary defect continued in Q-SPECT/CT in the third month of anticoagulant treatment in 58.3% of the patients diagnosed with PE due to COVID-19, and new defects developed in 6.3%. The persistence rate of segment defects was higher than that of subsegment defects. It was observed that the defects persisted more frequently in patients with a history of hospitalization due to COVID-19. Perfusion defects may still be present in patients diagnosed with PE due to COVID-19 in the presence of persistent dyspnea/chest pain/D-dimer elevation after 3 months of treatment. Perfusion defect persistence rates are higher in defects more proximal to the subsegment level and in people with severe COVID-19, and extended treatment should be considered in these patients.

Extended Anticoagulation After Pulmonary Embolism: A Multicenter Observational Cohort Analysis.

BackgroundPulmonary embolism (PE) has a long‐term risk of adverse events, which can be prevented by extended anticoagulation. We compared clinical characteristics and outcomes between patients treated with 2‐year extended anticoagulation and those who were not, in a population who had completed an initial phase of 3 to 6 months of anticoagulant therapy after acute PE.Methods and ResultsObservational cohort analysis of patients with PE who survived an initial phase of 3 to 6 months anticoagulation. Primary efficacy outcome was all‐cause death or recurrent venous thromboembolism. Primary safety outcome was major bleeding. In total, 858 (71.5%) patients were treated with and 341 (28.5%) were treated without extended anticoagulant therapy during the active study period. Age <65 years, intermediate‐high or high‐risk index PE, normal platelet count, and the absence of concomitant antiplatelet treatment were independently associated with the prescription of extended anticoagulation. The mean duration of the active phase was 2.1±0.3 years. The adjusted rate of the primary efficacy outcome was 2.1% in the extended group and 7.7% in the nonextended group (P<0.001) for patients treated with extended anticoagulant therapy. Rate of bleeding were similar between the extended anticoagulant group and the nonextended group.ConclusionsExtended oral anticoagulation over 2 and a half years after index PE seems to provide a net clinical benefit compared with no anticoagulation in patients with PE selected to receive extended anticoagulation. Randomized clinical trials are warranted to explore the potential benefit of extended anticoagulation in patients with PE, especially those with transient provoking factors but residual risk.

Anticoagulant-related nephropathy: Focus on novel agents. A review.

Anticoagulant-related nephropathy (ARN) is a novel and not well-studied cause of acute kidney injury (AKI). The prevalence of ARN varies significantly between studies and is estimated at 20% in patients treated with warfarin. Patients with ARN have a significantly higher mortality risk and an increased risk of chronic kidney disease (CKD). Unexplained AKI with hematuria are clinical manifestations of ARN. In most cases, ARN is diagnosed within the first 2 months of anticoagulant therapy, but later ARN occurrence is possible. Among the studied anticoagulants, most data concern warfarin toxicity, whereas cases of ARN caused by direct oral anticoagulants (DOACs) have also been presented. Tubular obstruction by red blood cell casts or hemoglobin and iron tubular toxicity are the postulated mechanisms of ARN. On the molecular level, the inhibition of thrombin and protease-activated receptor-1 (PAR-1), leading to endothelial susceptibility to damage or abnormal protein C endothelial signaling, is suggested to contribute to ARN. Older age, impaired kidney function, hypertension, and diabetes mellitus are the main risk factors for ARN, but their significance may differ between anticoagulants. From therapeutic options, the withdrawal of the anticoagulant and the administration of its antidote, as well as corticosteroids or N-acetylcysteine, are proposed. Since the number of patients with kidney diseases on anticoagulants increases, and DOACs are starting to be more useful in this group of patients, we aim to summarize the pathogenesis, clinical picture and possible ways of treatment of DOAC-induced ARN.

A Novel Doppler TRPG/AcT Index Improves Echocardiographic Diagnosis of Pulmonary Hypertension after Pulmonary Embolism.

Background: We hypothesized that a Doppler index, the ratio of tricuspid regurgitation peak gradient (TRPG) to pulmonary ejection acceleration time (AcT), improves the assessment of the echocardiographic probability of pulmonary hypertension in the identification of CTEPH and chronic thromboembolic pulmonary disease (CTED) in symptomatic patients after PE. Doppler echocardiography is recommended as the initial imaging tool for the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). Methods: We analyzed the data from 845 consecutive PE (468 women; 61 ± 18 years) survivors who completed at least 6 months of anticoagulation therapy. Here, 555 patients (325 women; 66 ± 16 years) reporting functional impairment (FI) underwent transthoracic echocardiography. We included 506 patients (297 women; age 63.4 ± 16.6 years) in whom both AcT and TRPG were available into the current study. The presence of a minimum of intermediate echocardiographic probability of PH necessitated the diagnosis of CTEPH. Results: Echocardiography revealed a high echocardiographic probability of PH in 69 (13.6%) and intermediate echocardiographic probability in 109 (21.5%) patients. CTEPH was diagnosed in 35 (6.9%) patients and CTED in 22 (4.3%) patients. TRPG/AcT was significantly higher in the combined CTEPH + CTED group than in those with other causes of FI (0.412 (0.100–2.197) vs. 0.208 (0.026–0.115), p < 0.001), and the area under the receiver operating characteristic curve of the TRPG/AcT for CTEPH + CTED was 0.804 (95% confidence interval (CI): 0.731–0.876). Importantly, multiple logistic regression showed that TRPG/AcT is a significant predictor of CTEPH + CTED after considering echocardiographic probability (odds ratio = 1.51, 95% CI: 1.25–1.91, p < 0.001). Conditional inference trees analysis revealed that TRPG/AcT > 0.595 identified patients with CTEPH or CTED with a positive predictive value of 78.6% and negative predictive value of 92.7%. Conclusions: A Doppler index TRPG/AcT improves the assessment of symptomatic PE survivors. TRPG/AcT > 0.6 indicates a high probability of CTEPH or CTED, whereas TRPG/AcT < 0.6 allows for the safe exclusion of CTEPH + CTED in patients with a low echocardiographic probability of PH.