Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), remains a significant public health burden in the USA with an estimated 1 200 000 VTE cases in 2020. Atherothrombosis refers to thrombosis in the setting of atherosclerotic cardiovascular disease and includes type I myocardial infarction (MI), ischaemic stroke, and acute limb events with an estimated 720 000 MIs annually in the USA. Despite the historical view of VTE and atherothrombosis as unrelated entities recognized by 'red vs. white clots', these conditions are closely interconnected and share many pathophysiological features and clinical risk factors. This review provides a critical appraisal of the current evidence for the relationship between VTE and atherothrombosis, exploring potential mechanisms and risk factors linking the disorders, recent discoveries from basic and translational research, clinical investigation highlighting their commonalities, as well as the therapies that address both.

This post hoc analysis of the Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism ( HI-PRO) randomized clinical trial investigates the impact of extended low-dose apixaban on symptomatic superficial vein thrombosis events in patients with provoked venous thromboembolism and enduring risk factors.

Rule-based natural language processing (NLP) tools can identify pulmonary embolism (PE) via radiology reports. However, their external validity remains uncertain.In this cross-sectional study, 1,712 hospitalized patients (with and without PE) at Mass General Brigham (MGB) hospitals (2016-2021) were analyzed. Two previously published NLP algorithms were applied to radiology reports to identify PE. Chart review by two physicians was the reference standard. We tested three approaches: (A) NLP applied to all patients; (B) NLP limited to radiology reports of patients with principal or secondary International Classification of Diseases 10th revision (ICD-10) PE discharge codes; and (C) NLP applied to patients with PE discharge codes or a Present-on-Admission (POA) indicator ("Y") for PE. All others were assumed PE-negative in Approaches B and C to minimize NLP false positives. Weighted estimates were derived from the MGB hospitalized cohort (n = 381,642) to calculate F1 scores (as the harmonic mean of sensitivity and positive predictive value [PPV]).In Approach A, both NLP tools showed high sensitivity (82.5%, 93.0%) and specificity (98.9%, 98.7%) but low PPV (60.3%, 59.6%). Approach B improved PPV (95.2%, 94.9%) but reduced sensitivity (74.1%, 76.2%), while Approach C preserved both high sensitivity (82.5%, 93.0%) and PPV (95.6%, 95.8%). Approach C demonstrated the best performance, yielding significantly higher F1 scores for both NLP tools (88.6%, 94.4%) compared with Approach A (69.7%, 72.6%) and Approach B (83.3%, 84.5%) (P < 0.001).The accuracy of PE detection improves when rule-based NLP algorithms are operationalized using administrative claims data in addition to radiology reports.

Background: Rule-based natural language processing (NLP) tools are easy to implement and can identify pulmonary embolism (PE) via radiology reports, but their accuracy is limited when used in isolation, and their external validity remains uncertain. Methods: In this cross-sectional study, we analyzed data from a prespecified sample of 1,712 hospitalized patients (with and without PE) at Mass General Brigham (MGB) hospitals (2016–2021) and applied two previously published NLP algorithms (Verma et al. and Johnson et al) to radiology reports to identify PE. Chart review by two independent physicians using pre-specified criteria was the reference standard. We tested three approaches: (A) NLP applied to all patients; (B) NLP limited to patients with primary or secondary International Classification of Diseases (ICD)-10 PE discharge codes; and (C) NLP applied to patients with PE discharge codes or a Present-on-Admission (POA) indicator (“Y” or “N”) for PE. All others were assumed PE-negative in Approaches B and C to minimize false positives with NLP. Weighted estimates were derived from the full MGB hospitalized cohort (n=381,642) to calculate F1 scores that summarize model performance by combining sensitivity and positive predictive value (PPV) [F1 = 2 x (PPV x sensitivity)/ (PPV + sensitivity)]. Results: In total, 7,708 (2.0%) patients had PE. In Approach A, both NLP models showed high sensitivity (82.5%, 93.0%) and specificity (98.9%, 98.7%) but low PPV (60.3%, 59.6%) (Figure). Approach B improved PPV (95.2%, 94.9%) at the cost of reduced sensitivity (74.1%, 76.2%), while Approach C preserved both high sensitivity (82.5%, 93.0%) and PPV (95.6%, 95.8%). Approach C demonstrated the best performance, yielding significantly higher F1 scores for both NLP models (88.6%, 94.4%) compared with Approach A (69.7%, 72.6%) and Approach B (83.3%, 84.5%) (P<0.001). Conclusions: The accuracy of PE detection improves when rule-based NLP models are operationalized within a screening framework using administrative claims data in addition to radiology reports.

Coronavirus disease 2019 (COVID-19) and active cancer are each independently associated with excess risk of thrombotic and cardiovascular events. However, data are limited regarding the risk of these events in outpatients with active cancer and concomitant COVID-19. Objectives:This study aimed to retrospectively examine the association between active cancer and thrombotic and cardiovascular outcomes among non-hospitalized patients with COVID-19. Methods:Data from the outpatient cohort with confirmed COVID-19 from the 10,420-patient multicenter U.S. CORONA-VTE Network registry were used. Active cancer was defined as having a malignancy diagnosis (excluding non-melanoma skin cancer) or receiving cancer-related treatment within the past year. Outcomes were independently adjudicated and included a composite of venous and arterial thromboembolism, and a composite of major adverse cardiovascular events, including thromboembolism, heart failure, myocarditis, new atrial fibrillation, and cardiovascular death within 90 days of COVID-19 diagnosis. Results:The registry included 6,576 outpatients, of whom 166 (2.5%) had active cancer (mean age 61 ± 16, 53% female). For outpatients with and without active cancer, the 90-day cumulative incidences of thromboembolism after developing COVID-19 were 4.2% and 1.2%, respectively (hazard ratio [HR]: 3.65; 95% confidence interval [CI]: 1.73-7.69, p  < 0.001). Corresponding 90-day cumulative incidences of cardiovascular events were 5.4% and 1.9% (HR: 2.97; 95% CI: 1.46-6.05, p  = 0.003). In adjusted analyses, non-hospitalized patients displayed an increased risk of thrombotic outcomes (HR: 2.48, 95% CI: 1.13-5.45, p  = 0.024) but not cardiovascular outcomes (HR: 1.76, 95% CI: 0.85-3.62, p  = 0.13). Conclusion:Outpatients with COVID-19 and active cancer demonstrated an increased hazard of thrombotic events compared with outpatients without cancer.

Background Patients with COVID‐19 are at risk of thrombotic and cardiovascular complications. Existing risk estimates derive from early COVID‐19 experiences. More recent event rates, temporal trends, and the association between vaccination status and cardiovascular outcomes remain unclear. Methods The CORONA‐VTE Network (COVID‐19 Registry to Assess Frequency, Risk Factors, Management, and Outcomes of Arterial and Venous Thromboembolic Complications) multicenter registry included patients with COVID‐19 from March 2020 to February 2024. A composite of venous and arterial thrombotic events and a composite of adjudicated cardiovascular events were assessed at 90 days after COVID‐19 diagnosis. Time‐to‐first‐event analyses were stratified by inpatients and outpatients and adjusted for competing risks. Outcomes were adjudicated by independent physicians. Results Of 11 165 patients, 4451 were inpatients (mean age, 65 years; 47% women) and 462 of 4451 were admitted to the intensive care unit. Among inpatients, the 90‐day cumulative incidences of thrombotic and cardiovascular events were 8.9% (95% CI, 8.0%–9.8%) and 15.6% (95% CI, 14.5%–16.7%), respectively. Corresponding estimates for patients in the intensive care unit were 20.0% (95% CI, 16.6%–24.0%) and 30.7% (95% CI, 26.8%–35.3%), while event rates were low among outpatients. There was an initial decline in cardiovascular events (adjusted hazard ratio [HR], 0.84; P=0.001) after the first COVID‐19 wave, with a subsequent catch‐up, with no significant linear change in cardiovascular events (adjusted Ptrend=0.634). Vaccination was associated with a reduced risk of cardiovascular events (adjusted HR, 0.75 [95% CI, 0.62–0.92]; P=0.005). Conclusions Thrombotic and cardiovascular events are common in hospitalized patients with COVID‐19, especially those in the intensive care unit, without a persistent decline over time. COVID‐19 vaccination was associated with a reduced risk of cardiovascular events.

COVID-19 is associated with an increased risk of venous thromboembolism (VTE) in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We utilized data from hospitalized patients in the CORONA-VTE Network, a United States multicenter registry of adult patients with PCR-confirmed COVID-19 (N = 3,844). The primary outcome was time-to-first event for a composite of adjudicated pulmonary embolism or deep vein thrombosis during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. We conducted cause-specific Cox regression analysis adjusted for the selected variables for each imputed dataset and pooled the estimated HRs for reporting (p < 0.05 for significance). VTE occurred in 206 patients, with a cumulative incidence of 5.3

BACKGROUND:Isolated subsegmental pulmonary embolism (issPE) is a commonly encountered diagnosis. Although the International Classification of Diseases (ICD)-10 codes are used for research, their validity for identifying issPE is unknown. Moreover, issPE diagnosis is challenging, and the findings from radiology reports may conflict with those from expert radiologists. METHODS:Based on prespecified criteria, 1734 medical records of adult patients hospitalized within the Mass General Brigham health system (2016-2021) were selected in three equal groups: (1) patients with principal discharge diagnosis codes for PE, (2) patients with secondary discharge diagnosis codes for PE, and (3) patients with no PE codes. The accuracy of ICD-10 codes for issPE was verified by two independent physicians and weighted by total hospitalizations. In a randomly selected sample of 70 patients, the accuracy of initial radiology reports was determined through a blinded re-evaluation by two expert radiologists. RESULTS:In weighted estimates, ICD-10 codes in primary or secondary discharge positions, compared with chart reviews, showed a low sensitivity (7.0 %) and positive predictive value (25.2 %). Evaluation by two expert radiologists noted that initial radiology reports were sensitive (97.1 %) for issPE but had a low specificity (40.0 %). Two (3.6 %) out of 55 patients with initial issPE reports did not have PE, while 19 (34.5 %) had more proximal PE. CONCLUSIONS:ICD-10 codes for issPE have poor sensitivity and positive predictive value and should not be used for research or quality improvement. Radiology reports for issPE may be inaccurate regarding the location or, less often, the presence of PE.

BACKGROUND:The appropriate duration of anticoagulation for venous thromboembolism (VTE) in patients who have a transient provoking factor (e.g., surgery, trauma, or immobility) and concomitant enduring risk factors is uncertain. METHODS:In this single-center, double-blind, randomized trial, adults with VTE after the occurrence of a transient provoking factor who had at least one enduring risk factor and had completed at least 3 months of anticoagulation were assigned to receive oral apixaban (at a dose of 2.5 mg twice daily) or placebo for 12 months. The primary efficacy outcome was the first symptomatic recurrent VTE. The primary safety outcome was the first episode of major bleeding according to the criteria of the International Society on Thrombosis and Hemostasis. RESULTS:A total of 600 patients underwent randomization (mean age, 59.5 years; female sex, 57.0%; non-White race, 19.2%). The trial population had a broad range of provoking factors and enduring risk factors. Symptomatic recurrent VTE occurred in 4 of the 300 patients (1.3%) in the apixaban group and in 30 of the 300 patients (10.0%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.04 to 0.36; P<0.001). Major bleeding occurred in 1 patient in the apixaban group and none in the placebo group. Clinically relevant nonmajor bleeding was observed in 14 of 294 patients (4.8%) in the apixaban group and in 5 of 294 patients (1.7%) in the placebo group (hazard ratio, 2.68; 95% CI, 0.96 to 7.43; P = 0.06). One patient in the apixaban group and 3 patients in the placebo group died, with no deaths attributed to cardiovascular or hemorrhagic causes. Nonhemorrhagic, nonfatal adverse events occurred in 6 patients (2.0%) in each group. CONCLUSIONS:Among patients with provoked VTE and enduring risk factors, low-intensity therapy with apixaban for 12 months resulted in a lower risk of symptomatic recurrent VTE than placebo, with a low risk of major bleeding. (Funded by Bristol-Myers Squibb-Pfizer Alliance; HI-PRO ClinicalTrials.gov number, NCT04168203.).

Direct oral anticoagulants (DOACs) have transformed the landscape of antithrombotic therapy in the past two decades. However, there is uncertainty about when they should or should not be used for treatment or prevention of thromboembolic events. DOACs have largely replaced warfarin for many patients with atrial fibrillation or venous thromboembolism who require anticoagulant therapy. In addition to noninferior efficacy, fewer drug-drug and food-drug interactions and improved convenience; DOACs have been shown to reduce the risk of intracranial hemorrhage. They have also received new indications compared with warfarin, such as cardiovascular risk reduction in patients with stable atherosclerotic diseases. However, there are some scenarios in which DOACs are associated with inferior efficacy or worse safety compared with standard treatment, such as warfarin. These include patients with mechanical heart valves, thrombotic antiphospholipid syndrome, and others. Although DOACs offer a streamlined and convenient option for the management of many patients with or at risk of thromboembolic events, their use should be avoided in certain high-risk scenarios. This minireview summarizes such conditions and those in which there is uncertainty for use of DOACs for particular diseases or particular patient subgroups.

Direct oral anticoagulants (DOACs) have become the preferred option for treatment of venous thromboembolism due to their favorable profile compared with other agents such as vitamin K antagonists or low-molecular-weight heparin. However, findings from randomized controlled trials suggest efficacy and/or safety concerns with DOAC use in some clinical contexts. This illustrated review will summarize indications where DOACs have proven efficacy and safety, situations where they fall short, and situations where uncertainty remains compared with other treatments for venous thromboembolism.

BACKGROUND:Many research investigations for pulmonary embolism (PE) rely on the International Classification of Diseases 10th Revision (ICD-10) codes for analyses of electronic databases. The validity of ICD-10 codes in identifying PE remains uncertain. OBJECTIVES:The objective of this study was to validate an algorithm to efficiently identify pulmonary embolism using ICD-10 codes. METHODS:Using a prespecified protocol, patients in the Mass General-Brigham hospitals (2016-2021) with ICD-10 principal discharge codes for PE, those with secondary codes for PE, and those without PE codes were identified (n = 578 from each group). Weighting was applied to represent each group proportionate to their true prevalence. The accuracy of ICD-10 codes for identifying PE was compared with adjudication by independent physicians. The F1 score, which incorporates sensitivity and positive predictive value (PPV), was assessed. Subset validation was performed at Yale-New Haven Health System. RESULTS:A total of 1712 patients were included (age: 60.6 years; 52.3% female). ICD-10 PE codes in the principal discharge position had sensitivity and PPV of 58.3% and 92.1%, respectively. Adding secondary discharge codes to the principal discharge codes improved the sensitivity to 83.2%, but the PPV was reduced to 79.1%. Using a combination of ICD-10 PE principal discharge codes or secondary codes plus imaging codes for PE led to sensitivity and PPV of 81.6% and 84.7%, respectively, and the highest F1 score (83.1%; P < .001 compared with other methods). Validation yielded largely similar results. CONCLUSION:Although the principal discharge codes for PE show excellent PPV, they miss 40% of acute PEs. A combination of principal discharge codes and secondary codes plus PE imaging codes led to improved sensitivity without severe reduction in PPV.

IntroductionPregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events.Materials & methodsWe analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and for men ≤45 years, as points of reference.ResultsAmong 6585 outpatients, 169 were pregnant at diagnosis. By 90-day follow-up, two pregnant women during the third trimester had lower extremity venous thrombosis, one deep and one superficial vein thrombosis. The cumulative incidence of thrombotic events was 1.20 % (95 % confidence interval [CI]: 0.0 to 2.84 %). Respective rates were 0.47 % (95 % CI: 0.14 % to 0.79 %) among non-pregnant women, and 0.49 % (95 % CI: 0.06 % to 0.91 %) among men ≤45 years. No non-thrombotic cardiovascular events occurred in pregnant women. The rates of cardiovascular events were 0.53 % (95 % CI: 0.18 to 0.87) among non-pregnant women, and 0.68 % (95 % CI: 0.18 to 1.18) in men aged ≤45 years.ConclusionsThrombotic and cardiovascular events are rare among outpatients with COVID-19. Although a higher event rate among outpatient pregnant women cannot be excluded, the absolute event rates are low and do not warrant population-wide cardiovascular interventions to optimize outcomes.