Dataset Information

Prevalence and Impact of Venous and Arterial Thromboembolism in Patients With Embolic Stroke of Undetermined Source With or Without Active Cancer.

ABSTRACT: Background An increased risk of acute ischemic stroke is recognized among patients with cancer. However, the mechanism behind cancer-related stroke is unclear. In this study, we determined the presence of associated venous thromboembolism and arterial thromboembolism and their clinical impact on patients with cancer-related stroke. Methods and Results Patients with embolic stroke of undetermined source with or without cancer were evaluated for venous thromboembolism (deep vein thrombosis [DVT] and/or pulmonary embolism) and arterial thromboembolism by using Doppler sonography to determine the presence of lower-extremity DVT and the microembolic signal of the symptomatic cerebral circulation, respectively. Infarct volume was determined by diffusion-weighted magnetic resonance imaging. The multivariable linear regression and Cox proportional hazard analysis were used to investigate the effect of DVT and microembolic signal on infarct volume and 1-year survival, respectively. Of 142 screened patients, 118 were included (37 with, 81 without cancer). Those with cancer had a higher prevalence of DVT or microembolic signal than did the noncancer group (62.2% versus 19.8%; P<0.001). Among patients with cancer-related stroke, DVT was associated with a greater infarct volume in magnetic resonance imaging (beta, 13.14; 95% CI, 1.62-24.66; P=0.028). Presence of DVT (hazard ratio, 16.79; 95% CI, 2.05-137.75; P=0.009) and microembolic signal (hazard ratio, 8.16; 95% CI, 1.36-48.85; P=0.022) were independent predictors of poor 1-year survival. Conclusions Patients with cancer-associated embolic stroke of undetermined source have an elevated risk of associated venous thromboembolism and arterial thromboembolism, both of which have a significant negative impact on 1-year survival. The results of this study may enhance our understanding of cancer-associated stroke and improve risk stratification of patients with this disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov/.Unique identifier: NCT02212496.

SUBMITTER: Ha J

PROVIDER: S-EPMC6898837 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Prevalence and Impact of Venous and Arterial Thromboembolism in Patients With Embolic Stroke of Undetermined Source With or Without Active Cancer.

Ha Jongmok J Lee Mi Ji MJ Kim Suk Jae SJ Park Bo-Yong BY Park Hyunjin H Cho Soohyun S Chung Jong-Won JW Seo Woo-Keun WK Kim Gyeong-Moon GM Bang Oh Young OY Chung Chin-Sang CS

Journal of the American Heart Association 20191023 21

Background An increased risk of acute ischemic stroke is recognized among patients with cancer. However, the mechanism behind cancer-related stroke is unclear. In this study, we determined the presence of associated venous thromboembolism and arterial thromboembolism and their clinical impact on patients with cancer-related stroke. Methods and Results Patients with embolic stroke of undetermined source with or without cancer were evaluated for venous thromboembolism (deep vein thrombosis [DVT] a ...[more]

PMID: 31640456

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Project description:ObjectivePrevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies.MethodsCRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective.ResultsCompared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years).ConclusionsAnticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

Project description:Background and purposeOne-fifth of ischemic strokes are embolic strokes of undetermined source (ESUS). Their theoretical causes can be classified as cardioembolic versus noncardioembolic. This distinction has important implications, but the categories' proportions are unknown.MethodsUsing data from the Cornell Acute Stroke Academic Registry, we trained a machine-learning algorithm to distinguish cardioembolic versus non-cardioembolic strokes, then applied the algorithm to ESUS cases to determine the predicted proportion with an occult cardioembolic source. A panel of neurologists adjudicated stroke etiologies using standard criteria. We trained a machine learning classifier using data on demographics, comorbidities, vitals, laboratory results, and echocardiograms. An ensemble predictive method including L1 regularization, gradient-boosted decision tree ensemble (XGBoost), random forests, and multivariate adaptive splines was used. Random search and cross-validation were used to tune hyperparameters. Model performance was assessed using cross-validation among cases of known etiology. We applied the final algorithm to an independent set of ESUS cases to determine the predicted mechanism (cardioembolic or not). To assess our classifier's validity, we correlated the predicted probability of a cardioembolic source with the eventual post-ESUS diagnosis of atrial fibrillation.ResultsAmong 1083 strokes with known etiologies, our classifier distinguished cardioembolic versus noncardioembolic cases with excellent accuracy (area under the curve, 0.85). Applied to 580 ESUS cases, the classifier predicted that 44% (95% credibility interval, 39%-49%) resulted from cardiac embolism. Individual ESUS patients' predicted likelihood of cardiac embolism was associated with eventual atrial fibrillation detection (OR per 10% increase, 1.27 [95% CI, 1.03-1.57]; c-statistic, 0.68 [95% CI, 0.58-0.78]). ESUS patients with high predicted probability of cardiac embolism were older and had more coronary and peripheral vascular disease, lower ejection fractions, larger left atria, lower blood pressures, and higher creatinine levels.ConclusionsA machine learning estimator that distinguished known cardioembolic versus noncardioembolic strokes indirectly estimated that 44% of ESUS cases were cardioembolic.

Project description:BackgroundFrom a therapeutic viewpoint, it is important to differentiate the underlying causes of embolism in patients with cryptogenic stroke, such as aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. We investigated the clinical and radiological characteristics of these 3 common causes of cryptogenic embolism to develop models for decision making in etiologic workups.Methods and resultsA total of 321 consecutive patients with acute infarcts from cryptogenic embolism were included. Patients were divided into 3 groups-aortic arch atheroma (n=40), patent foramen ovale (n=153), and paroxysmal atrial fibrillation (n=128)-based on extensive cardiologic workups. We used a multinomial logistic regression analysis to detect the clinical and diffusion-weighted imaging factors associated with the probability of aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. Clinical and radiological features differed among the groups. The patent foramen ovale group had a healthy vascular risk factor profile and showed posterior circulation involvement compared with other groups (P<0.01). In contrast, paroxysmal atrial fibrillation-related strokes had higher initial National Institutes of Health Stroke Scale (NIHSS) scores and larger lesions than the other groups (P<0.001). The aortic arch atheroma group had clinical features similar to those of the paroxysmal atrial fibrillation group but showed small lesions scattered in multiple vascular territories (P<0.001). Multivariate regression analysis revealed that age, initial NIHSS score, lesion size (≥20 mm), multiple (≥3) lesions, and involvement of posterior circulation or multiple vascular territories differentiated the 3 groups (pseudo, R(2)=0.656). The prediction ability of this model was validated in the external validation cohort (n=117, area under the curve 0.78).ConclusionsOur data indicate that patients with cryptogenic embolic stroke show distinct clinical and radiological features depending on the underlying causes.

Dataset Information

Prevalence and Impact of Venous and Arterial Thromboembolism in Patients With Embolic Stroke of Undetermined Source With or Without Active Cancer.

Publications

Prevalence and Impact of Venous and Arterial Thromboembolism in Patients With Embolic Stroke of Undetermined Source With or Without Active Cancer.

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