Background: A large proportion of patients experience functional limitations after an acute episode of venous thromboembolism (VTE). Recently, the post-VTE functional status (PVFS) scale was... Show moreBackground: A large proportion of patients experience functional limitations after an acute episode of venous thromboembolism (VTE). Recently, the post-VTE functional status (PVFS) scale was proposed to capture these limitations. We performed a prospective cohort study to validate this scale.Methods: The PVFS scale, PROMIS physical function 10a, EQ-5D-5L, and disease-specific quality of life (VEINES-QOL/Sym, PEmb-QoL) were assessed within three weeks of VTE diagnosis and after a median (IQR) follow-up of 13.4 (12.7-15.9) weeks. To evaluate construct validity of the PVFS scale, we determined correlations of PVFS scale with the other health measurements and investigated differences in patients above/below 70 years. Responsiveness was evaluated with a linear regression model, predicting change in PROMIS with change in PVFS scale.Results: We included 211 patients (median (IQR) age: 55.1 (44.1-67.6) years, 40 % women). Pulmonary em-bolism was diagnosed in 105 (49.8 %) patients and 62.6 % of events were unprovoked. The PVFS scale correlated with PROMIS physical function (Spearman's rho (r):-0.67 and-0.63, p < 0.001) and EQ-5D-5L index (r =-0.61 and-0.61, p < 0.001) at baseline and follow-up. Furthermore, PVFS correlated moderately to strongly with disease-specific quality of life. Patients >70 years had significantly higher PVFS grades at follow-up (median (IQR): 2 (0-3) vs. 1 (0-2), p = 0.010). Changes in PVFS scale over time were significantly associated with changes in PROMIS physical function.Conclusions: The PVFS scale showed adequate construct validity and responsiveness in a prospective cohort study of patients with VTE, suggesting that it can be incorporated as additional health measurement and outcome parameter in research and clinical practice. Show less
Jong, C.M.M. de; Blondon, M.; Ay, C.; Buchmuller, A.; Beyer-Westendorf, J.; Biechele, J.; ... ; TEAM VTE Investigators 2022
Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking.... Show morePreliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. Show less
The International Consortium for Health Outcomes Measurement assembled an international working group of venous thromboembolism experts and patient representatives to develop a standardised minimum... Show moreThe International Consortium for Health Outcomes Measurement assembled an international working group of venous thromboembolism experts and patient representatives to develop a standardised minimum set of outcomes and outcome measurements for integration into clinical practice and potentially research to support clinical decision making and benchmarking of quality of care. 15 core outcomes important to patients and health-care professionals were selected and categorised into four domains: patient-reported outcomes, long term consequences of the disease, disease-specific complications, and treatment-related complications. The outcomes and outcome measures were designed to apply to all patients with venous thromboembolism aged 16 years or older. A measurement tool package was selected for inclusion in the core standard set, with a minimum number of items to be measured at predefined timepoints, which capture all core outcomes. Additional measures can be introduced to the user by a cascade opt-in system that allows for further assessment if required. This set of outcomes and measurement tools will facilitate the implementation of the use of patient-centred outcomes in daily practice. Show less
Background: COVID-19 survivors face the risk of long-term sequelae including fatigue, breathlessness, and functional limitations. Pulmonary rehabilitation has been recommended, although formal... Show moreBackground: COVID-19 survivors face the risk of long-term sequelae including fatigue, breathlessness, and functional limitations. Pulmonary rehabilitation has been recommended, although formal studies quantifying the effect of rehabilitation in COVID-19 patients are lacking. Methods: We conducted a prospective observational cohort study including consecutive patients admitted to an outpatient pulmonary rehabilitation center due to persistent symptoms after COVID-19. The primary endpoint was change in 6-min walk distance (6MWD) after undergoing a 6-week interdisciplinary individualized pulmonary rehabilitation program. Secondary endpoints included change in the post-COVID-19 functional status (PCFS) scale, Borg dyspnea scale, Fatigue Assessment Scale, and quality of life. Further, changes in pulmonary function tests were explored. Results: Of 64 patients undergoing rehabilitation, 58 patients (mean age 47 years, 43% women, 38% severe/critical COVID-19) were included in the per-protocol-analysis. At baseline (i.e., in mean 4.4 months after infection onset), mean 6MWD was 584.1 m (+/- 95.0), and functional impairment was graded in median at 2 (IQR, 2-3) on the PCFS. On average, patients improved their 6MWD by 62.9 m (+/- 48.2, p < 0.001) and reported an improvement of 1 grade on the PCFS scale. Accordingly, we observed significant improvements across secondary endpoints including presence of dyspnea (p < 0.001), fatigue (p < 0.001), and quality of life (p < 0.001). Also, pulmonary function parameters (forced expiratory volume in 1 s, lung diffusion capacity, inspiratory muscle pressure) significantly increased during rehabilitation. Conclusion: In patients with long COVID, exercise capacity, functional status, dyspnea, fatigue, and quality of life improved after 6 weeks of personalized interdisciplinary pulmonary rehabilitation. Future studies are needed to establish the optimal protocol, duration, and long-term benefits as well as cost-effectiveness of rehabilitation. Show less
Klok, F.A.; Ageno, W.; Ay, C.; Back, M.; Barco, S.; Bertoletti, L.; ... ; Pruszczyk, P. 2022
This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a... Show moreThis position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control. Show less
Winter, M.A. de; Dorresteijn, J.A.N.; Ageno, W.; Ay, C.; Beyer-Westendorf, J.; Coppens, M.; ... ; Nijkeuter, M. 2021
Background Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not... Show moreBackground Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice.Objectives To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model.Methods In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED").Results Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED" showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration).Conclusion Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED," but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated. Show less
Mahe, I.; Agnelli, G.; Ay, C.; Bamias, A.; Becattini, C.; Carrier, M.; ... ; Laporte, S. 2021
Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them... Show moreCancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed >= 6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (beta=80%; alpha one-sided=0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding. Show less
Roth, P.; Pace, A.; Rhun, E. le; Weller, M.; Ay, C.; Moyal, E.C.J.; ... ; ESMO Guidelines Comm 2021
Background:Patients with pulmonary embolism (PE) may suffer from long-term consequences, including decreased functional capacity. Data on pulmonary rehabilitation (PR) in patients with PE are... Show moreBackground:Patients with pulmonary embolism (PE) may suffer from long-term consequences, including decreased functional capacity. Data on pulmonary rehabilitation (PR) in patients with PE are scarce, and no data on outpatient PR are available so far.Methods:We analyzed data of 22 PE patients who attended outpatient PR due to exertional dyspnea. Patients underwent a multi-professional 6-week PR program. The primary outcome was change in 6-min walk test (6MWT). Secondary outcomes included changes in strength and endurance tests. To assess long-term benefits, follow-up was performed a median of 39 months after PR.Results:Patients started PR a median of 19 weeks after the acute PE event. Their median age was 47.5 years, 33% were women and all presented with NYHA (New York Heart Association) class II and higher. After PR, patients showed significant and clinically relevant improvements in 6MWT (mean difference: 49.4 m [95% CI 32.0-66.8]). Similarly, patients increased performance in maximum strength, endurance and inspiratory muscle strength. At long-term follow-up, 78% of patients reported improved health.Conclusion:We observed significant improvements in exercise capacity in PE patients undergoing outpatient PR. The majority of patients also reported a long-term improvement in health status. Prospective studies are needed to identify patients who would benefit most from structured PR. Show less
ObjectiveTo investigate the characteristics and outcome of abnormal vaginal bleeding in women receiving edoxaban or warfarin for treatment of venous thromboembolism (VTE).Design and settingPost hoc... Show moreObjectiveTo investigate the characteristics and outcome of abnormal vaginal bleeding in women receiving edoxaban or warfarin for treatment of venous thromboembolism (VTE).Design and settingPost hoc analysis of the Hokusai-VTE study, a multicentre, randomised, double-blind trial comparing edoxaban with warfarin for acute symptomatic VTE.PopulationWomen below 50years receiving edoxaban or warfarin for treatment of VTE.MethodsWe collected data on diagnostic measures, treatment, and clinical outcome of abnormal vaginal bleeding events.Main outcome measuresOccurrence of major and clinically relevant nonmajor (CRNM) abnormal vaginal bleeding events.ResultsIn all, 628 women aged under 50years were treated with edoxaban and 665 with warfarin. The rate of abnormal vaginal bleeding was 15/100 person-years (py) (95%CI 11-19) in women receiving edoxaban and 9/100py (95%CI 6-12) in the warfarin group (hazard ratio: 1.7, 95% CI 1.1-2.5). Major abnormal vaginal bleeding occurred in eight (1.3%) women on edoxaban and in three (0.9%) women receiving warfarin [odds ratio (OR) 2.8; 95% CI 0.8-10.8], and CRNM abnormal vaginal bleeding occurred in 53 (8.4%) women treated with edoxaban and in 37 (5.6%) on warfarin therapy (OR 1.6, 95%CI 1.0-2.4). Over 85% of all vaginal bleeds were characterised by heavy menstrual bleeding. Major bleeds frequently required treatment, and in more than 75% of patients anticoagulant therapy was adjusted. The severity of clinical presentation and course of major and CRNM bleeds was mild in most patients.ConclusionsAbnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin. Reassuringly, most events could be managed conservatively and had a mild outcome.Tweetable abstractAbnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin.Tweetable abstract Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin. Show less
