Prospective Multicenter International Registry of Ultrasound-Facilitated Catheter-Directed Thrombolysis in Intermediate-High and High-Risk Pulmonary Embolism (KNOCOUT PE).

BACKGROUND: Prior clinical trials have demonstrated the efficacy of ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk pulmonary embolism (PE) using reduced thrombolytic doses and shorter infusion durations. However, utilization and safety of such strategies in broader PE populations remain unclear. The KNOCOUT PE (The EKoSoNic Registry of the Treatment and Clinical Outcomes of Patients With Pulmonary Embolism) registry is a multicenter international registry designed to study the treatment of acute PE with USCDT, with focus on safety outcomes. METHODS: The KNOCOUT PE prospective cohort included 489 patients (64 sites internationally) with acute intermediate-high or high-risk PE treated with USCDT between March 2018 and June 2020. Principal safety outcomes were independently adjudicated International Society on Thrombosis and Haemostasis major bleeding at 72 hours post-treatment and mortality within 12 months of treatment. Additional outcomes included change in right ventricular/left ventricular ratio and quality of life measures over 12 months. RESULTS: Mean alteplase (r-tPA [recombinant tissue-type plasminogen activator]) infusion duration was 10.5 hours. Mean total r-tPA dose was 18.1 mg, with 31.0% of patients receiving ≤12 mg. Major bleeding events within 72 hours occurred in 1.6% (8/489) of patients. One patient experienced worsening of a preexisting subdural hematoma after USCDT and therapeutic anticoagulation, which ultimately required surgery. All-cause mortality at 30 days was 1.0% (5/489). Improvement in PE quality of life score was observed with a 41.1% (243/489, 49.7%) and 44.2% (153/489, 31.3%) mean relative reduction by 3 and 12 months, respectively. CONCLUSIONS: In a prospective observational cohort study of patients with intermediate-high and high-risk PE undergoing USCDT, mean r-tPA dose was 18 mg, and the rates of major bleeding and mortality were low. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03426124.

Meningioma resection and venous thromboembolism incidence, management, and outcomes.

Background: Meningioma resection is associated with the risk of venous thromboembolism (VTE). Objectives: To determine the incidence and risk factors for VTE following meningioma resection and VTE outcomes based on the type and timing of anticoagulation. Methods: From 2011 to 2019, 901 consecutive patients underwent meningioma resection. We retrospectively evaluated the postoperative incidence of VTE and bleeding. For VTE, we determined the treatment strategy and rate of VTE complications and bleeding. Results: Pharmacologic prophylaxis was administered to 665 (73.8%) patients. The cumulative incidence for total postoperative VTE was 8.7% (95% CI: 6.9%-10.6%), and for symptomatic VTE was 6.0% (95% CI: 4.6%-7.7%). A multivariable model identified the following independent predictors of symptomatic VTE: history of VTE, obesity, and lack of pharmacologic prophylaxis. Following postoperative VTE, 58 (74.3%) patients received therapeutic anticoagulation either initially (33.3%) or after a median delay of 23.5 days (41.0%). Symptomatic recurrent VTE occurred in 13 (16.6%) patients. Following VTE, the use of subtherapeutic anticoagulation was associated with a lower rate of total VTE extension than no anticoagulation (17.5% vs 42.9%, OR 0.28, 95% CI: 0.09-0.93). In total, 14 patients (1.6%) experienced clinically relevant bleeding: 4 received therapeutic anticoagulants, 8 received prophylactic anticoagulation, and 2 received no anticoagulation. Among patients with VTE, 4 (5.1%) experienced bleeding. Conclusion: Recognition of risk factors for VTE following meningioma resection may help improve approaches to thromboprophylaxis. The management of postoperative VTE is highly variable, but most VTE patients are ultimately treated with therapeutic anticoagulants.

Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism: Results of an Expert Consensus Panel.

In clinical practice, direct oral anticoagulants (DOACs) are increasingly used for venous thromboembolism treatment and prevention. A substantial proportion of patients with venous thromboembolism are also obese. International guidance published in 2016 stated that DOACs could be used in standard doses in patients with obesity up to a body mass index (BMI) of 40 kg/m2, but should not be used in those with severe obesity (BMI >40 kg/m2) owing to limited supporting data at the time. Although updated guidance in 2021 removed this limitation, some health care providers still avoid DOACs even in patients with lower levels of obesity. Furthermore, there are still evidence gaps regarding treatment of severe obesity, the role of peak and trough DOAC levels in these patients, use of DOACs after bariatric surgery, and appropriateness of DOAC dose reduction in the setting of secondary venous thromboembolism prevention. This document describes proceedings and outcomes of a multidisciplinary panel convened to review these and other key issues regarding DOAC use for treatment or prevention of venous thromboembolism in individuals with obesity.

Risk of Recurrent Venous Thromboembolism in Selected Subgroups of Men: A Danish Nationwide Cohort Study.

Background Although men are considered at high risk for recurrent venous thromboembolism (VTE), sex-specific data on prognostic factors are lacking. We estimated the cumulative recurrence risks associated with clinical characteristics and comorbidities known or suspected to be associated with the development of VTE recurrence: major surgery, trauma, history of cancer, rheumatic disorder, ischemic heart disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes, chronic renal disease, varicose veins, alcohol-related diseases, and arterial hypertension. Methods We linked nationwide Danish health registries to identify all incident VTE in- and outpatients in men from 2008 through 2018. Recurrent VTE risk 2 years after anticoagulant discontinuation was calculated using the Aalen-Johansen estimator, stratified by age above/below 50 years. Results The study included 13,932 men with VTE, of whom 21% ( n = 2,898) were aged <50 years. For men aged <50 years with at least one of the clinical characteristics, 2-year recurrence risk ranged from 6% (major surgery) to 16% (history of cancer). For men ≥50 years with at least one of the characteristics, recurrence risk ranged from 7% (major surgery) to 12% (ischemic heart disease, chronic obstructive pulmonary disease, and chronic renal disease). Men aged <50 and ≥50 years without the clinical characteristics all had a recurrence risk of 10%. Discussion We demonstrated a 2-year recurrence risk of at least 6%, regardless of age category and disease status, in this nationwide cohort of men with VTE. The recurrence risk must be balanced against bleeding risk. However, the high recurrence risk across all subgroups might ultimately lead to greater emphasis on male sex in future guidelines focusing on optimized secondary VTE prevention.

Arterial Thrombotic Complications in COVID-19: A Case of Renal Infarction.

COVID-19 infection has been associated with thrombotic complications, especially venous thromboembolism. Although arterial thrombotic complications are rarely seen in these patients, we report the case of a 43-year-old patient who developed thrombosis of the main branch of the left renal artery, causing partial infarction of the left kidney associated with severe pain. He had no risk factors for thrombosis except for COVID-19 infection. We excluded any possible condition usually associated with renal artery thrombosis/embolism (i.e., cardiovascular, oncological, hematological, or rheumatic). The thrombosis resolved after a combination of anticoagulant and anti-platelet therapy. This case highlights the importance of the risk of recurrence of thrombosis in patients with a recent history of COVID-19, even after hospital discharge, improvement of the initial thrombotic event, and clearance of SARS-CoV-2 infection.

The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study.

BACKGROUND: Thrombosis is common among patients with cancer. Primary thromboprophylaxis guided by the Khorana score is endorsed by guidelines but recommendations rely mainly on data from patients treated with chemotherapy. OBJECTIVES: To explore if the Khorana score could risk stratify patients with cancer treated with immune checkpoint inhibitors according to risk of venous and arterial thrombosis. PATIENTS/METHODS: The study population and Khorana score were defined using administrative Danish health registries. The primary outcome was 6-month risk of venous thromboembolism after initiation of checkpoint inhibitor treatment. Secondary outcomes were arterial thrombosis and any thromboembolic event. Death was considered a competing risk event. RESULTS: Among 3946 patients with cancer initiating checkpoint inhibitor treatment without other indications for anticoagulation, the overall 6-month incidence of venous thromboembolism was 2.6% (95% confidence interval [CI]: 2.1-3.1). Risks were 2.1% (95% CI: 1.5-3.0), 2.6% (95% CI: 2.0-3.4), and 3.7% (95% CI: 2.1-5.9) in low (score 0), intermediate (score 1-2), and high risk (score ≥3) Khorana categories, respectively. Among patients eligible for primary thromboprophylaxis according to guidelines (Khorana score ≥2), risk of venous thromboembolism was 4.1% (95% CI: 3.1-5.4). Higher Khorana risk category was also associated with higher 6-month risk of both arterial thrombosis and any thromboembolic events. CONCLUSIONS: The Khorana score was able to risk stratify patients with cancer treated with immune checkpoint inhibitors according to 6-month risk of thromboembolic events. Risks of venous thromboembolism were lower than in randomized thromboprophylaxis trials, thus questioning the absolute benefit of routine primary thromboprophylaxis in an unselected population of patients treated with immune checkpoint inhibitors.

Patients with myeloproliferative neoplasms and COVID-19 have increased rates of arterial thrombosis.

Background: Both coronavirus disease-2019 (COVID-19) and myeloproliferative neoplasms (MPNs) are associated with systemic inflammation and risk of thrombosis. Risk of thrombosis in patients with COVID with and without MPNs has not been extensively studied. Methods: Retrospective cohort study of 44 patients with MPNs and 1114 patients without MPNs positive for SARS-COV-2. Outcomes were arterial thrombosis (AT), venous thromboembolism (VTE), bleeding, and death. Time-to-event analysis was performed using competing risk regression model and Cox proportional hazards. Results: AT occurred more frequently in patients with MPN (7% vs. 1%, p = 0.03). Rates of VTE (7% vs. 5%, p = 0.73), bleeding (7% vs. 2%, p = 0.06), and death (9% vs. 6%, p = 0.32) were similar. MPN patients were older and had more cardiovascular comorbidities. After time-to-event competing-risk regression adjusting for age, MPN patients had higher risk of AT (subdivision hazards ratio 3.95, 95% CI 1.09-14.39) but not VTE, bleeding, or death. Conclusions: Among patients with COVID-19, MPN patients had higher risk of arterial thrombosis but not VTE, bleeding, and death compared with non-MPN patients. Larger studies are needed to confirm our findings given the limited sample size.

Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants: A Review.

Importance: Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs. Observations: Among 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities. Conclusions and Relevance: Dose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

Optimal reperfusion strategy in acute high-risk pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis.

BACKGROUND: The optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial. METHODS: We conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes. RESULTS: We identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the "other strategies" group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237-0.816) (p=0.009; I2=35.2%) versus other reperfusion strategies and 0.368 (95% CI 0.185-0.733) (p=0.004; I2=32.9%) for surgical embolectomy versus thrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the "other strategies" group (OR 1.27, 95% CI 0.54-2.96; I2=7.7%). The meta-regression model did not identify any relationship between the covariates "more than one pulmonary reperfusion therapy", "ECMO implantation before pulmonary reperfusion therapy", "clinical presentation of PE" or "cancer-associated PE" and the associated outcomes. CONCLUSIONS: The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation.

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy.

The Khorana score is recommended for guiding primary venous thromboembolism (VTE) prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored the competing risk of death, hereby potentially overestimating VTE risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated 6-month cumulative incidence of VTE stratified by Khorana levels. Analyses were conducted with and without considering death as a competing risk using the Kaplan-Meier method vs the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40 218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1 to 2), and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding 6-month risks of VTE were 1.5% (95% confidence interval [CI], 1.3-1.7), 2.8% (95% CI, 2.6-3.1), and 4.1% (95% CI, 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), the 6-month risk was 3.6% (95% CI, 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk-stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to the risk of VTE, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials.

Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in Patients with Provoked Venous Thromboembolism and Enduring Risk Factors: Rationale and Design of the HI-PRO Trial.

Patients with acute venous thromboembolism (VTE) in the setting of transient provoking factors are typically treated with short-term anticoagulation. However, the risk of recurrence may be increased in the presence of enduring risk factors. In such patients, the optimal duration of treatment remains uncertain. HI-PRO is a single-center, double-blind randomized trial. Patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) following a major provoking factor, including major surgery or major trauma, who completed at least 3 months of standard-dose therapeutic anticoagulation and have at least one enduring risk factor (such as obesity or heart failure) will be considered for inclusion. Patients will be randomized to apixaban 2.5 mg twice daily or placebo for 12 months. The primary efficacy outcome will be symptomatic recurrent VTE-a composite of DVT and/or PE at 12 months after randomization. Secondary efficacy outcomes include a composite of death due to cardiovascular causes, nonfatal myocardial infarction, stroke or systemic embolism, major adverse limb events, or coronary or peripheral ischemia requiring revascularization at 12 months, and individual components of these outcomes. The primary safety outcome is major bleeding according to the International Society on Thrombosis and Haemostasis definition. The study plans to enroll 600 patients (300 per arm) to have 80% power for detecting a 75% relative risk reduction in the primary outcome. Active recruitment began in March 2021. HI-PRO will provide clinically meaningful data on whether patients with provoked VTE and enduring risk factors have fewer adverse clinical outcomes if prescribed low-intensity extended-duration anticoagulation.

Impact of Atrial Fibrillation on In-Hospital Mortality and Stroke in Acute Aortic Syndromes.

BACKGROUND: Acute aortic syndromes may present with a number of cardiovascular complications, including atrial fibrillation. We assessed the prevalence of atrial fibrillation in patients presenting with acute aortic syndromes and evaluated atrial fibrillation's association with in-hospital mortality and stroke. METHODS: Consecutive patients with acute aortic syndromes admitted to a single tertiary care center from January 2015 to March 2020 were included. We identified patients with atrial fibrillation on the presenting electrocardiogram. RESULTS: A total of 309 patients with acute aortic syndromes were included in our analyses: 148 (48%) presented with Stanford type A and 161 (52%) with Stanford type B acute aortic syndromes. Twenty-seven (8.7%) patients had atrial fibrillation on the presenting electrocardiogram: 12 (44%) with type A and 15 (56%) with type B acute aortic syndromes. Patients with atrial fibrillation were older, more likely to be white, had a higher frequency of history of cancer, peripheral artery disease, cerebrovascular disease, and heart failure with preserved ejection fraction, compared with those without atrial fibrillation. Acute aortic syndromes patients with atrial fibrillation had higher frequencies of in-hospital mortality compared with those without atrial fibrillation (40.7% vs 12.4%, P < .0001). However, stroke frequencies did not differ between the 2 groups. CONCLUSION: In patients presenting with acute aortic syndromes and atrial fibrillation, we observed higher frequencies of in-hospital mortality, without differences in the frequencies of stroke.

An Original Risk Score to Predict Early Major Bleeding in Acute Pulmonary Embolism: The Syncope, Anemia, Renal Dysfunction (PE-SARD) Bleeding Score.

BACKGROUND: Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management. RESEARCH QUESTION: Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding? STUDY DESIGN AND METHODS: From a multicenter prospective registry including 2,754 patients, we performed post hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally, using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared with that of the VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), and BACS (Bleeding, Age, Cancer, and Syncope) models. RESULTS: Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%; 95% CI, 2.39%-3.72%): Syncope (+1.5); Anemia, defined as hemoglobin <12 g/dL (+2.5); and Renal Dysfunction, defined as glomerular filtration rate <60 mL/min (+1 point) (SARD). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% (95% CI, 50.29%-54.11%) of patients were classified as low bleeding-risk (score, 0 point), 35.2% (95% CI, 33.39%-37.04%) intermediate-risk (score, 1-2.5 points), and 12.6% (95% CI, 9.30%-16.56%) high-risk (score >2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97% (95% CI, 0.53%-1.62%) in the low-risk to 8.93% (95% CI, 6.15%-12.44%) in the high-risk group. C-index was 0.74 (95% CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not. INTERPRETATION: The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE.

Update on Guidelines for the Management of Cancer-Associated Thrombosis.

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer. Over the past 2 decades, enormous advances have been made in the management of CAT. The growing evidence base informing practice has led to the publication of a number of guidelines and guidance documents on the diagnosis and treatment of CAT. The goal of this review is to examine the latest versions of evidence-based guidelines, highlighting the differences and similarities in their methodology, their disease-specific content, and recommendations for management. Our analysis shows that for most clinical topics, the different guidelines provide roughly similar management advice. However, there are a number of important clinical topics in CAT that are not currently covered by the existing guidelines. We think inclusion of these topics in future versions of the guidelines will facilitate ongoing efforts to optimize the care of patients with CAT. IMPLICATIONS FOR PRACTICE: Cancer-associated thrombosis (CAT) is a common complication in patients with cancer. This review examines the differences and similarities of the current CAT guidelines methods and recommendations. Current guidelines largely agree on many aspects of CAT management. However, there are a number of topics in CAT that are not currently included in guidelines where evidence-based guidance would be very helpful for clinicians. Coverage of these topics in future guidelines is encouraged to optimize clinical practice.

Identification and Outcomes of Hospitalized Medically Ill Patients Who Are Candidates for Extended Duration Thromboprophylaxis.

Background Extended duration thromboprophylaxis (ET) for approximately 30 days can effectively and safely reduce venous thromboembolism (VTE) risk in appropriately selected medically ill patients. We sought to estimate the proportion of hospitalized medically ill patients potentially qualifying for ET and assess their post-discharge clinical and economic outcomes using a large claims database. Methods Using MarketScan claims from January 2012 to September 2018, we identified medically ill patients hospitalized with a primary diagnosis of heart failure, respiratory insufficiency, ischemic stroke, infection, or inflammatory disease and ≥1-additional risk factor for VTE. Patients < 40 years old, a length-of-stay < 3 or >30 days, receiving oral anticoagulation prior to index hospitalization or having an indication for full-dose anticoagulation were excluded, as were patients deemed high-risk for bleeding due to active, in-hospital treated cancer, gastroduodenal ulcer or bleeding within the prior 3 months, bronchiectasis, pulmonary cavitation or hemorrhage, or dual antiplatelet therapy use. Results We identified 2,782,988 patients ≥40 years of age and admitted for a high-risk medical illness. Of these, 724,531 patients (26.0%) were identified as ET candidates. Patients' VTE risk appeared highest in the first 30 days post-discharge (1,532/724,531, 0.2%). Adjusted post-index hospitalization costs (2018 US$) for patients with a VTE within 30 days were higher than those without VTE (Δ = $32,623 at 30 days, Δ = $43,325 at 90 days, Δ = $53,668 at 365 days; p < 0.001 for all). Conclusion Post-discharge VTE in high-risk patients with medical illness is associated with substantially increased costs.

Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review.

IMPORTANCE: Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event. OBSERVATIONS: PubMed and Cochrane databases were searched for English-language studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies. Risk factors for venous thromboembolism (VTE), such as older age, malignancy (cumulative incidence of 7.4% after a median of 19 months), inflammatory disorders (VTE risk is 4.7% in patients with rheumatoid arthritis and 2.5% in those without), and inherited thrombophilia (factor V Leiden carriers with a 10-year cumulative incidence of 10.9%), are associated with higher risk of VTE. Patients with signs or symptoms of lower extremity DVT, such as swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%), should undergo assessment of pretest probability followed by D-dimer testing and imaging with venous ultrasonography. A normal D-dimer level (ie, D-dimer <500 ng/mL) excludes acute VTE when combined with a low pretest probability (ie, Wells DVT score ≤1). In patients with a high pretest probability, the negative predictive value of a D-dimer less than 500 ng/mL is 92%. Consequently, D-dimer cannot be used to exclude DVT without an assessment of pretest probability. Postthrombotic syndrome, defined as persistent symptoms, signs of chronic venous insufficiency, or both, occurs in 25% to 50% of patients 3 to 6 months after DVT diagnosis. Catheter-directed fibrinolysis with or without mechanical thrombectomy is appropriate in those with iliofemoral obstruction, severe symptoms, and a low risk of bleeding. The efficacy of direct oral anticoagulants-rivaroxaban, apixaban, dabigatran, and edoxaban-is noninferior to warfarin (absolute rate of recurrent VTE or VTE-related death, 2.0% vs 2.2%). Major bleeding occurs in 1.1% of patients treated with direct oral anticoagulants vs 1.8% treated with warfarin. CONCLUSIONS AND RELEVANCE: Greater recognition of VTE risk factors and advances in anticoagulation have facilitated the clinical evaluation and treatment of patients with DVT. Direct oral anticoagulants are noninferior to warfarin with regard to efficacy and are associated with lower rates of bleeding, but costs limit use for some patients.

Predictors of Treatment Response Following Ultrasound-Facilitated Catheter-Directed Thrombolysis for Submassive and Massive Pulmonary Embolism: A SEATTLE II Substudy.

BACKGROUND: Little is known about which factors predict improvement in clinical and imaging parameters among patients undergoing catheter-directed thrombolysis for submassive or massive pulmonary embolism. The identification of such predictors may allow for more appropriate patient selection for ultrasound-facilitated catheter-directed thrombolysis. METHODS: We conducted a retrospective cohort analysis of patients from the SEATTLE II trial (Prospective, Single-Arm, Multi-Center Trial of EkoSonic Endovascular System and Activase for Treatment of Acute Pulmonary Embolism) to identify clinical characteristics that independently predict pulmonary artery pressures, right ventricular-to-left ventricular (RV/LV) diameter ratio, and modified Miller angiographic index following ultrasound-assisted catheter-directed thrombolysis. Eligible patients had submassive or massive pulmonary embolism and an RV/LV diameter ratio ≥0.9 on chest computed tomography. Multivariable linear regression was used to identify independent clinical predictors of each outcome. RESULTS: One hundred fifty patients with massive (n=31) or submassive (n=119) pulmonary embolism were enrolled. Mean (±SD) baseline and postprocedure RV/LV diameter ratio, pulmonary artery systolic pressure, and modified Miller Score were 1.59 (±0.39) and 1.14 (±0.2), 51.45 (±16.0), and 37.47 (±11.9), and 23.0 (±5.7) and 15.7 (±5.9), respectively. The multivariable model adjusted R2 for absolute change in RV/LV ratio, pulmonary artery systolic pressure, modified Miller Score was 0.71, 0.57, and 0.43, respectively. After adjusting for age, gender, and baseline RV/LV ratio, pulmonary artery systolic pressure, and modified Miller Score, patients with higher body mass index, renal or hepatic dysfunction, active smoking, or a higher baseline heart rate showed less improvement. CONCLUSIONS: Patients with more life-threatening pulmonary embolism may derive the greatest benefit from ultrasound-assisted, catheter-directed thrombolysis.