Influence of primary cancer site on clinical outcomes of anticoagulation for associated venous thromboembolism.

INTRODUCTION: The outcome of anticoagulation for cancer-associated venous thromboembolism (Ca-VTE) differs according to cancer location, but data are limited and inconsistent. MATERIALS AND METHODS: Patients with acute venous thromboembolism (VTE) enrolled between 03/01/2013 and 04/30/2021 were followed prospectively to assess VTE recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and death. RESULTS: There were 1702 (45.3 %) patients with Ca-VTE including: gastrointestinal (n = 340), pancreatic (n = 223), hematologic (n = 188), genitourinary (n = 163), lung (n = 139), ovarian (n = 109), breast (n = 97), renal (n = 75), prostate (n = 73), hepatobiliary (n = 70), brain (n = 57), and other cancers (n = 168); 2057 VTE patients had no cancer (NoCa-VTE). Hepatobiliary cancer had the highest VTE recurrence (all rates 100 person-years) of all cancers and higher compared to NoCa-VTE (13.69, p = 0.01), while the MB rate, although numerically higher (15.91), was not different (p = 0.09). Another 3 cancers had higher VTE recurrence but similar MB rates compared to NoCa-VTE: genitourinary [(9.59, p = 0.01) and (7.03, p = 1.0)], pancreatic [(9.74, p < 0.001) and (5.47, p = 1.00)], and hematologic [(5.29, p = 0.05) and (3.59, p = 1.0)]. Renal cancer had the highest rate of MB among all cancers and was higher than that of NoCa-VTE (16.49; p < 0.001), with no difference in VTE recurrence (1.62; p = 1.0). VTE recurrence and MB rates were not significantly different between NoCa-VTE and gastrointestinal, lung, breast, prostate, and brain cancers. CRNMB rates were similar and mortality higher in Ca-VTE patients, except for prostate and breast cancer, compared to NoCa-VTE. CONCLUSIONS: Significant differences in clinical outcomes indicate that anticoagulation strategies may need to be tailored to the primary cancer location.

Survival Implications of Thrombus Recurrence or Bleeding in Cancer Patients Receiving Anticoagulation for Venous Thromboembolism Treatment.

BACKGROUND: Study aims were to analyze prospectively collected data from patients with cancer-associated venous thromboembolism (VTE) to determine the impact of VTE recurrence and anticoagulant-related bleeding on all-cause mortality. PATIENTS/METHODS: Consecutive cancer patients with acute VTE treated with anticoagulants (March 1, 2013-November 30, 2021) were included in this analysis. Anticoagulant therapy-associated VTE recurrences, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were assessed for their impact on all-cause mortality outcomes. RESULTS: This study included 1,812 cancer patients with VTE. Of these, there were 97 (5.4%) with recurrent VTE, 98 (5.4%) with major, and 104 (5.7%) with CRNMB while receiving anticoagulants. Recurrent VTE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.16-2.00; p = 0.0028), major bleeding (HR: 1.82; 95% CI: 1.41-2.31; p = 0.006), and CRNMB (HR; 1.38; 95% CI: 1.05-1.81; p = 0.018) each adversely influenced mortality outcomes. Deep vein thrombosis as the incident thrombotic event type was associated with VTE recurrence (HR: 1.78; 95% CI: 1.08-2.89; p = 0.02). Neither cancer type nor stage, chemotherapy, or Ottawa risk category influenced VTE recurrence. Higher body weights (HR: 1.01; 95% CI: 1.00-1.01; p = 0.005) were associated with increased major bleeding, while high Ottawa scores (HR: 0.66; 95% CI: 0.46-0.96; p = 0.03) and apixaban treatment (HR: 0.62; 95% CI: 0.45-0.84; p = 0.002) were associated with fewer major bleeding outcomes. CONCLUSION: Among cancer patients receiving anticoagulant therapy for VTE, adverse outcomes such as VTE recurrence, major bleeding, or CRNMB increase mortality risk by 40 to 80%. Identifying variables predicting these outcomes may help risk-stratify patients with poor prognosis.

Incidental pulmonary embolism in cancer and noncancer patients: Prospective cohort study.

BACKGROUND: Clinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear. METHODS: Demographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020). RESULTS: Out of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person-years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p = .50), with cancer (4.16 vs. 4.89, p = .370), and without cancer patients (0.89 vs. 2.80, p = .25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p = .03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p = .006) even after adjustment (p = .05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p = .03), but not after adjustment (p = .974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p = .007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients. CONCLUSION: iPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.

Pulmonary artery capacitance and pulmonary vascular resistance as prognostic indicators in acute pulmonary embolism.

Aims: The non-invasive calculation of right ventricular (RV) haemodynamics as pulmonary artery (PA) capacitance (PAC) and pulmonary vascular resistance (PVR) have proved to be feasible, easy to perform, and of high prognostic value. We, therefore, evaluated whether baseline PAC and PVR could predict clinical outcomes for patients with acute pulmonary embolism (PE). Methods and results: We prospectively followed 373 patients [mean (standard deviation) age, 64.1 (14.9) years; 58.4% were men, and 27.9% had cancer] who had acute PE and transthoracic echocardiography within 1 day of diagnosis from 1 March 2013 through 30 June 2020. Pulmonary artery capacitance was calculated as left ventricular stroke volume/(PA systolic pressure - PA diastolic pressure). Pulmonary vascular resistance was calculated as (tricuspid regurgitant velocity/RV outflow tract velocity time integral) × 10 + 0.16. These two variables were calculated retrospectively from the values obtained with transthoracic echocardiography. Pulmonary artery capacitance was acquired in 99 (27%) patients and PVR in 65 (17%) patients. Univariable and bivariable logistic regression analyses, and receiver operating characteristic curves were used to evaluate the ability of these haemodynamic measurements to predict mortality up to 6 months. After using bivariable models to adjust individually for age, cancer, and pulmonary hypertension. Pulmonary vascular resistance was associated with all-cause mortality at 3 months [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.61-0.86; P = 0.01], and 6 months (AUC 0.81; 95% CI 0.69-0.91; P ≤ 0.03). Pulmonary artery capacitance was associated with all-cause mortality at 30 days (AUC 0.95; 95% CI 0.82-0.99; P < 0.001) and 3 months (AUC 0.84; 95% CI 0.65-0.99; P = 0.003). Conclusion: Non-invasive measurement of RV haemodynamics could provide prognostic information of patients with acute PE. Pulmonary artery capacitance and PVR are potentially important predictors of all-cause mortality in these patients and should be explored in future studies.

Single versus multiple and incidental versus symptomatic subsegmental pulmonary embolism: clinical characteristics and outcome.

It remains unexplored if the clinical picture and outcome of subsegmental pulmonary embolism (SSPE) differ between single versus multiple, and incidental versus symptomatic embolism. Consecutive patients anticoagulated for SSPE at the Mayo Thrombophilia Clinic (03/01/2013-12/31/2020) were followed forward to assess venous thromboembolism (VTE) recurrence, mortality, major bleeding, and clinically relevant non-major bleeding (CRNMB); expressed as a rate per 100 person-years. Among 3878 VTE patients, 1541 had pulmonary embolism including 224 (14.6%) with SSPE either single (n = 139) or multiple (n = 85; 46 bilateral and 39 unilateral emboli); 134 had incidental and 90 symptomatic SSPE. Patients with single were less often symptomatic and less often had coexisting DVT than multiple SSPE. Patients with incidental had a two-fold higher frequency of cancer compared to symptomatic SSPE. During the study period, 1 patient with single and 2 with multiple SSPE had VTE recurrence (rate of 1.14 vs 3.63, p = 0.280). Single SSPE patients experienced 2 episodes of major bleeding (rate of 2.36) while the multiple SSPE group had no major bleeding. Seven patients in each group had CRNMB events (rate of 8.20 vs 13.58 for single and multiple SSPE, respectively, p = 0.282). Patients with single SSPE had a higher death rate compared to multiple SSPE (43.07 vs 22.22, p = 0.031) but no difference was noted after adjusting for cancer (p = 0.388). Also, incidental had similar clinical outcomes to symptomatic SSPE.Interpretation Anticoagulated SSPE patients with single and multiple as well as incidental and symptomatic have a different clinical profile but similar clinical outcomes.

Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban, Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism.

OBJECTIVE: To compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE). PATIENTS AND METHODS: Consecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB). RESULTS: In the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37). CONCLUSION: Apixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03504007.

Outcome of anticoagulation in isolated distal deep vein thrombosis compared to proximal deep venous thrombosis.

BACKGROUND: Isolated, distal deep vein thrombosis (IDDVT) is thought to have low rates of propagation, embolization, and recurrence compared with proximal DVT (PDVT), but the data are limited. OBJECTIVES: The objective of this study was to assess outcomes among patients with IDDVT compared with PDVT. PATIENTS/METHODS: Consecutive patients with ultrasound-confirmed acute DVT (March 1, 2013-August 1, 2020) were identified by reviewing the Mayo Clinic Gonda Vascular Center and VTE Registry databases. Patients were divided into two groups depending on the DVT location (isolated, distal vs. proximal DVT). Outcomes including venous thromboembolism (VTE) recurrence, major bleeding, and death were compared by thrombus location and anticoagulant therapy, warfarin vs. direct oral anticoagulant (DOAC). RESULTS: Isolated, distal deep vein thrombosis (n = 746) was more often associated with recent surgery, major trauma, or confinement (p < .001), whereas patients with PDVT (n = 1176) were more frequently unprovoked, had a prior history of VTE, or active cancer (p < .001). There was no overall difference in VTE recurrence or major bleeding between groups during follow-up. Patients with IDDVT had a higher death rate at 3 months (p = .001) and when propensity scored for cancer (p = .003). Independent predictors of mortality included warfarin (vs. DOAC) therapy, increasing age, and active cancer. DOAC therapy resulted in lower VTE recurrence, major bleeding, and death rates in both groups. CONCLUSION: Outcomes of IDDVT including VTE recurrence and bleeding rates were similar to PDVT despite higher early mortality rates. Outcomes for both groups were positively influenced by the use of DOACs.

Delayed anticoagulation in venous thromboembolism: Reasons and associated outcomes.

OBJECTIVE: We assessed the number of cases with delayed anticoagulation initiation, explored the reasons for the delay, and its impact on outcome in patients with acute venous thromboembolism (VTE) treated in an organized setting of treatment initiation and continuous, prospective follow-up. METHODS: Patients with anticoagulation initiation delay >24 hours were identified within the cohort of patients with acute VTE enrolled in the Mayo Clinic Venous Thromboembolism Registry between 2013 and 2020. The reasons for treatment delay were explored by reviewing the electronic database. VTE recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared to those with no anticoagulation delay. RESULTS: Of 2378 patients with acute VTE, 100 (4.2%) experienced an anticoagulation delay. We identified seven reasons for treatment delays: deferring anticoagulation initiation to specialists (n = 38), thrombocytopenia (n = 10), planned or recent procedure (n = 16), active or recent bleeding (n = 12), missed diagnosis (n = 7), logistics (n = 6), and patient decision (n = 4). In seven cases, no reason was identified. We identified modifiable reasons for anticoagulation delay in 55%. At 90-day follow-up, patients with anticoagulation delay had a higher rate of mortality and major bleeding. VTE recurrence and CRNMB were not statistically different compared to those without anticoagulation delay. After adjustment for age, weight, and cancer, hazard ratios (HRs) for VTE recurrence and major bleeding remained elevated but not to a statistically significant level. CONCLUSION: In the setting of a highly organized system of anticoagulation initiation, the incidence of treatment delay is low. Yet most delays could be avoided. A low number of cases provide insufficient power to evaluate the clinical consequences of anticoagulation initiation delay; however, elevated HR for VTE recurrence and major bleeding suggest association and need for further investigation.

Von Willebrand Factor and ADAMTS13 as Predictors of Adverse Outcomes in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Von Willebrand factor (VWF) elevation correlates with the left atrial blood stasis in nonvalvular atrial fibrillation (NVAF). However, the long-term impact of elevated VWF in patients with NVAF is not well established. METHODS: To assess the impact of VWF and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in conjunction with echocardiographic measures of left atrium blood stasis on clinical outcomes, 414 NVAF prospectively recruited (October 4, 2007, to April 27, 2009) patients were followed for 3 years. VWF antigen, VWF activity, ADAMTS13 activity, and echocardiographic findings were assessed at baseline. Thromboembolism (TE) (stroke/transient ischemic attack (TIA)), myocardial infarction, or TE of other locations), major bleeding, clinically relevant nonmajor bleeding, and all-cause mortality were assessed by clinical follow-up, questionnaire, or telephone communication. RESULTS: Among 374 patients (mean age, 63.4 ± 12.7 years; 25% females) who had complete follow-up data, there were 33 TE in 32 patients (8.6%), 18 deaths (5.1%), and 33 bleeding events (21 major bleeding and 12 clinically relevant nonmajor bleeding) in 25 patients (6.7%). VWF antigen was predictive of TE in the univariate examination (hazard ratio [HR]: 1.007, 95% confidence interval [CI]: 1.002, 1.013, P = 0.011) but not in multivariate analysis. VWF was an independent predictor of all-cause mortality (HR: 1.011, 95% CI: 1.003, 1.020, P = 0.011) and a composite of TE and all-cause mortality (HR: 1.006, 95% CI: 1.001, 1.012, P = 0.039) in multivariate analysis. ADAMTS13 was not predictive of clinical outcomes in multivariate analysis. CONCLUSIONS: Among patients with NVAF, VWF is an independent predictor of poor outcomes including death and a composite of death and TE. As such, VWF measure may help identify high-risk patients and provide further stratification beyond CHA2DS2-VASc assessment.

CONTEXTE: Une élévation du facteur de Von Willebrand (FVW) concorde avec une stase sanguine dans l'oreillette gauche dans la fibrillation auriculaire non valvulaire (FANV). Les répercussions à long terme d'un taux élevé du FVW chez les patients présentant une FANV ne sont toutefois pas bien établies. MÉTHODOLOGIE: Pour évaluer les répercussions sur les résultats cliniques du FVW et d'une désintégrine et métalloprotéinase de motif type 1 (ADAMTS13) conjointement avec les mesures échocardiographiques de la stase sanguine dans l'oreillette gauche, 414 patients atteints de FANV ont été inscrits de façon prospective (du 4 octobre 2007 au 27 avril 2009) pour faire l'objet d'un suivi de 3 ans. L'antigène du FVW, l'activité du FVW, l'activité d'ADAMTS13, et les résultats de l'échocardiographie ont été évalués au départ. La thromboembolie (TE) (accident vasculaire cérébral/accident ischémique transitoire, infarctus du myocarde, ou TE survenant ailleurs), l'hémorragie majeure, l'hémorragie non majeure pertinente sur le plan clinique et la mortalité toutes causes ont été évaluées au suivi clinique, par questionnaire, ou lors d'un appel téléphonique. RÉSULTATS: Parmi les 374 patients (âge moyen : 63,4 ± 12,7 ans; 25 % de femmes) ayant participé au suivi jusqu'à sa fin, on a relevé 33 TE chez 32 patients (8,6 %), 18 décès (5,1 %) et 33 événements hémorragiques (21 hémorragies majeures et 12 hémorragies non majeures pertinentes sur le plan clinique) chez 25 patients (6,7 %). L'antigène du FW était prédictif d'une TE selon l'analyse univariée (risque relatif [RR] : 1,007; intervalle de confiance [IC] à 95 % : de 1,002 à 1,013; p = 0,011), mais non selon l'analyse multivariée. Le FVW était un facteur prédictif indépendant de la mortalité toutes causes (RR : 1,011; IC à 95 % : de 1,003 à 1,020; p = 0,011) et des événements regroupés de TE et de mortalité toutes causes (RR : 1,006; IC à 95 % : de 1,001 à 1,012; p = 0,039) dans l'analyse multivariée. La protéase ADAMTS13 ne constituait pas un facteur prédictif des résultats cliniques dans l'analyse multivariée. CONCLUSIONS: Parmi les patients présentant une FANV, le FVW était un facteur prédictif indépendant de résultats défavorables, notamment de décès et des événements regroupant les décès et la TE. La mesure du FVW pourrait donc aider à cibler les patients à risque élevé, et permettre une stratification au-delà de l'évaluation du score CHA2DS2-VASc.

Calf vein thrombosis outcomes comparing patients with and without cancer.

Distal or calf deep vein thrombosis (DVT) are said to have low rates of propagation, embolization, and recurrence. The objective of this study was to determine outcomes among cancer patients with calf DVT compared to those without cancer. Consecutive patients with ultrasound confirmed acute calf DVT (3/1/2013-8/10/2019) were assessed for venous thromboembolism (VTE) recurrence and bleeding outcomes compared by cancer status. There were 830 patients with isolated calf DVT; 243 with cancer and 587 without cancer. Cancer patients were older (65.9 ± 11.4 vs. 62.0 ± 15.9 years; p = 0.006), with less frequent recent hospitalization (31.7% vs. 48.0%; p < 0.001), surgery (30.0% vs. 38.0%; p = 0.03), or trauma (3.7% vs. 19.9%; p < 0.001). The four most common cancers included hematologic malignancies (20.6%), lung (11.5%), gastrointestinal (10.3%), and ovarian/GYN (9.1%). Nearly half of patients had metastatic disease (43.8%) and 57% were receiving chemotherapy. VTE recurrence rates were similar for patients with (7.1%) and without cancer (4.0%; p = 0.105). Major bleeding (6.3% vs. 2.3%; p = 0.007) were greater for cancer patients while clinical relevant non major bleeding rates did not differ (7.1% vs. 4.6%; p = 0.159). In this retrospective analysis, cancer patients with calf DVT have similar rates of VTE recurrence but higher major bleeding outcomes compared to patients without cancer.

Calf Vein Thrombosis Comparison of Outcomes for Axial and Muscular Venous Thrombosis.

BACKGROUND: The objective of this study was to characterize clinical features and outcomes among patients with calf deep vein thrombosis (DVT) limited to the muscular veins compared with axial veins. METHODS: Consecutive patients with ultrasound confirmed acute DVT involving the calf veins (January 1, 2016-August 1, 2018) were identified from the Gonda Vascular Center ultrasound database. Patients were divided into axial or muscular groups based on thrombus location. Demographics, management, and outcomes were compared. RESULTS: Over the study period, there were 647 patients with calf DVT equally distributed between axial (n = 321) and muscular (n = 326) locations. Within these groups, peroneal and soleal veins were most commonly involved. Nearly all cases were provoked (97%). Synchronous pulmonary embolism (PE) were more common for axial (30.8%) compared to muscular groups (20.2%; p = 0.001); nearly one-third had no pulmonary symptoms. Anticoagulation for a median of 3 months was initiated for 85.5% of both groups. Venous thromboembolism (VTE) recurrence was more common in the axial group (15.9% vs. 7.1%, p = 0.0015) including more frequent DVT propagation (9.4% vs. 3.1%; p = 0.0017) and PE (3.4% vs. 0.6%; p = 0.0168). Major bleeding, clinically relevant nonmajor bleeding, and mortality rates did not differ between groups. Withholding anticoagulation led to more frequent thrombus propagation in the axial group (3.4% vs. 0.9%; p = 0.029). CONCLUSION: Several important features distinguish muscular from axial DVT. Axial DVT are more likely to have an associated PE and are more likely to experience recurrent VTE, particularly if anticoagulation is withheld.

Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

OBJECTIVES: To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg. METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. RESULTS: Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01). CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism.

OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome. METHODS: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories. RESULTS: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category. CONCLUSION: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03504007.

Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism.

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism.

OBJECTIVE: To compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE). PATIENTS AND METHODS: Consecutive patients enrolled in the Mayo Thrombophilia Clinic Registry (between March 1, 2013, and January 30, 2018) and treated with apixaban or rivaroxaban for acute VTE were followed forward in time. The primary efficacy outcome was VTE recurrence. The primary safety outcome was major bleeding; the second safety outcome was clinically relevant nonmajor bleeding (CRNMB); and the third was a composite of major bleeding or CRNMB. RESULTS: Within the group of 1696 patients with VTE enrolled, 600 (38%) were treated either with apixaban (n=302, 50%) or rivaroxaban (n=298, 50%) within the first 14 days of VTE diagnosis and who completed at least 3 months of therapy or had a study event. Recurrent VTE was diagnosed in 7 patients (2.3%) treated with apixaban and in 6 (2%) treated with rivaroxaban (adjusted hazard ratio [aHR], 1.4; 95% CI, 0.5-3.8). Major bleeding occurred in 11 patients (3.6%) receiving apixaban and in 9 patients (3.0%) receiving rivaroxaban (aHR, 1.2; 95% CI, 0.5-3.2). Clinically relevant nonmajor bleeding was diagnosed in 7 patients (2.3%) receiving apixaban and in 20 (6.7%) receiving rivaroxaban (aHR, 0.4; 95% CI, 0.2-0.9). The rates of composite major bleeding or CRNMB were similar (aHR, 0.6; 95% CI, 0.3-1.2). Most study events occurred in patients with cancer. CONCLUSION: In the setting of a standardized, guideline-directed, patient-oriented clinical practice, the efficacy and safety of apixaban and rivaroxaban for the treatment of acute VTE were comparable.

Kinetics of saturated, monounsaturated, and polyunsaturated fatty acids in humans.

Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-¹³C]linoleate, [U-¹³C]oleate, and [U-¹³C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase-generated fatty acids. Study 2 used an intravenous lipid emulsion to increase FFA concentrations during infusion of linoleate and palmitate tracers. In study 1, there were no differences in spillover of the three fatty acids for the low-palmitate meal, but linoleate spillover was greater than oleate or palmitate for the high-palmitate meal. In studies 1 and 2, clearance was significantly greater for linoleate than for the other FFAs. There was a negative correlation between clearance and concentration for each fatty acid in the two studies. In study 1, concentration and spillover correlated positively for oleate and palmitate but negatively for linoleate. In conclusion, linoleate spillover is greater than that of other fatty acids under some circumstances. Linoleate clearance is greater than that of palmitate or oleate, indicating a need for caution when using a single FFA to infer the behavior of all fatty acids.

Spillover of Fatty acids during dietary fat storage in type 2 diabetes: relationship to body fat depots and effects of weight loss.

Spillover of lipoprotein lipase-generated fatty acids from chylomicrons into the plasma free fatty acid (FFA) pool is an important source of FFA and reflects inefficiency in dietary fat storage. We measured spillover in 13 people with type 2 diabetes using infusions of a [(3)H]triolein-labeled lipid emulsion and [U-(13)C]oleate during continuous feeding, before and after weight loss. Body fat was measured with dual energy X-ray absorptiometry and computed tomography. Participants lost ∼14% of body weight. There was an ∼38% decrease in meal-suppressed FFA concentration (P < 0.0001) and an ∼23% decrease in oleate flux (P = 0.007). Fractional spillover did not change (P = NS). At baseline, there was a strong negative correlation between spillover and leg fat (r = -0.79, P = 0.001) and a positive correlation with the trunk-to-leg fat ratio (R = 0.56, P = 0.047). These correlations disappeared after weight loss. Baseline leg fat (R = -0.61, P = 0.027) but not trunk fat (R = -0.27, P = 0.38) negatively predicted decreases in spillover with weight loss. These results indicate that spillover, a measure of inefficiency in dietary fat storage, is inversely associated with lower body fat in type 2 diabetes.