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Risk of recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with first unprovoked VTE event according to sex
Source publication
OBJECTIVES To determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, and the cumulative incidence for recurrent VTE up to 10 years.
DESIGN Systematic review and meta-analysis.
DATA SOURCES Medline, Embase, and the Cochrane Ce...
Context in source publication
Context 1
... men with a first unprovoked VTE, the pooled rate of recurrent VTE per 100 person years after discontinuation of anticoagulation was 11.9 events (95% confidence interval 9.6 to 14.4; I 2 =76%) in the first year, 7.3 events (5.3 to 9.5; I 2 =63%) in the second year, 4.4 events/year (95% confidence interval 3.2 to 5.7; I 2 =60%) in years 3-5, and 3.8 events/year (1.6 to 6.9; I 2 =89%) in years 6-10 (table 3). The cumulative incidence for recurrent VTE in men was 18.3% (95% confidence interval 14.4% to 22.5%) at 2 years, 28.6% (table 3). ...Citations
... VTE events may be provoked by a major transient risk factor, a minor transient risk factor, a persistent risk factor; or may be unprovoked. 8 Data from prior meta-analyses indicate that the pooled rate of recurrent VTE after discontinuation of anticoagulant treatment in patients with unprovoked VTE is 10.3 events per 100 person-year (95% CI, 8.3-12.1) in the first year, 22 whereas the pooled rate of recurrent VTE in patients with VTE provoked by a non-surgical factor is 5.8 per 100 person-year (95% CI, 3.2-8.3). 23 In our work, the rate of recurrent VTE in patients with COVID-19associated VTE was lower than rate in VTE provoked by a non-surgical factor. ...
... Second, this study lacks an efficacy comparison group, making it potentially challenging to determine if discontinuing anticoagulant treatment is effective compared to continuation, although we do have reference cohorts through which we can compare the rate of recurrent VTE. 22,23 Nevertheless, comparing our results with data from systematic reviews and metaanalyses, if done properly and considering potential limitations, can be a valid strategy for assessing the effectiveness of a clinical decision, especially when conducting a clinical trial is not feasible or is complicated. Third, it is possible that during the study period, there were cases of COVID-19 that went undetected because tests were not conducted. ...
Background
The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE.
Methods
A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued.
Findings
Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3–20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5–4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2–4.2). No patient died of recurrent PE (0%, 95% CI: 0–7.6%). Subgroup analyses showed that patients with diagnosis in 2021–2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45–5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19–4.49) had significantly higher rates of VTE recurrences.
Interpretation
In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings.
Funding
10.13039/100004339Sanofi and Rovi, Sanofi Spain.
... Pulmonary embolism (PE), the most severe clinical presentation of venous thromboembolism (VTE), occurs in one patient over 1000 every year and represents the third leading cause of cardiovascular death [1][2][3]. The main complications of PE are recurrent non-fatal and fatal VTE, and long-term sequelae (chronic thromboembolic pulmonary disease with or without pulmonary hypertension) [4]. In 50% of cases, PE occurs in the absence of clinical circumstances (termed "unprovoked PE") [5]. ...
Introduction
The pathophysiology of residual pulmonary vascular obstruction (RPVO) and recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism (PE) remains poorly understood. The purpose was to evaluate fibrinolytic and tissue remodeling markers as indicators of RPVO and recurrence after a first unprovoked PE.
Methods
Analyses were conducted in the 18 to 70-year-old patients included in the PADIS-PE trial, with a pulmonary vascular obstruction (PVO) index ≥30% at PE diagnosis. After an initial six-month vitamin K antagonist treatment, patients were randomised to receive placebo or warfarin for 18 months, assessed for the absence or presence of residual pulmonary vascular obstruction (RPVO < or ≥5%, respectively) and followed during two years. Quantitative assessment of fibrinolytic (D-dimer, tPA, uPA, TFPI) and tissue remodeling (TGFß1) markers, and a tissue-factor-based turbidimetric clot lysis assay (CLA) were performed one month after warfarin discontinuation.
Results
Among the 371 patients included in the PADIS-PE trial, 23 were eligible. Six (26%) patients presented RPVO, symptomatic recurrent VTE occurred in nine (39%) patients. Clot formation and lysis parameters were not associated with RPVO. TGFß1 plasma levels were higher in patients with RPVO. Clot formation potential measured with CLA was higher in patients with recurrent VTE. No association between recurrent VTE and TGFß1 was observed. In multivariable analysis, time to peak was associated with VTE recurrence.
Conclusion
In adult patients with a first unprovoked PE and a PVO index ≥30%, TGFß1 plasma level was associated with RPVO, whereas clot formation parameters measured with CLA were associated with VTE recurrence.
... The incidence of VTE in malignancies is influenced by factors such as the primary location of the tumor, its stage, and histological features. The highest-risk cancers include pancreatic, lung, stomach, and brain cancers, as well as hematologic malignancies, while the lowest-risk cancers include prostate and breast cancers [26][27][28][29]. The likelihood of developing VTE increases proportionally to the severity of the cancer. ...
Venous thromboembolism (VTE) is one of the life-threatening complications in cancer patients, the incidence of which is affected by the patient and malignancy-related variables. Location, type, therapeutic route, stage, grade, and non-supportive treatment of the cancer are the most important VTE risk factors. Patient age, ethnicity, and concomitant genetic or acquired comorbidities or thrombophilias are known risk factors for VTE in cancer. All high-risk cancer patients admitted to hospitals or treated as outpatients should receive VTE prophylaxis. Low molecular weight heparin is the main treatment for active malignant VTE. Vitamin K antagonists and non-Vitamin K-dependent oral anticoagulants are used in stable, non-bleeding cancer patients. Anticoagulation should be continued until the cancer is treated or at least controlled. Over the past two decades, randomized clinical and observational trials have improved the pathogenesis and therapeutic knowledge of VTE, but many challenges remain. The lack of an optimal primary prophylaxis method for inpatients and outpatients in oncology and the care of cancer-associated VTE in standard and high-bleeding risk groups are examples for which more clinical research on cancer-associated thrombosis is necessary to address these issues. In this review, we describe the pathogenesis, factors that increase the risk of VTE, and the comparison between the effectiveness of available anticoagulants in the treatment and prevention of VTE in cancer patients.
... Venous thromboembolism (VTE), encompassing pulmonary embolism (PE) and deep vein thrombosis (DVT), is a common disease that places a substantial burden on both patients and society [1][2][3][4][5][6][7]. The occurrence of a thrombotic event is associated with adverse outcomes such as VTE recurrence and bleeding complications due to anticoagulation therapy [8][9][10]. In addition, both DVT and PE are associated with longterm sequelae, including postthrombotic syndrome and post-PE syndrome [11][12][13][14]. ...
... Epidemiological modelling for six European countries estimated nearly 762 000 symptomatic VTE events/ year and over 370 000 VTE-related deaths/year [1]. Risk factors for VTE (other than major surgery and trauma) [2] include increasing age [3], cancer [3], hospitalization [4] and previous history of VTE [5]. ...
Background
The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice.
Methods
Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed.
Results
Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9–63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes.
Conclusions
This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.
... A systematic review and meta-analysis of studies on patients presenting with an unprovoked VTE reported a rate of VTE recurrence of 10.1% at one year after anticoagulation therapy discontinuation. 14 In 2022, our group evaluated patients requiring longterm anticoagulation for recurrent VTE, receiving DOACs as per VTE secondary prophylaxis. 15 In this retrospective, single-center study, 209 patients were included. ...
Background: Direct oral anticoagulants (DOACs) are widely used for the treatment and secondary prophylaxis of venous thromboembolism (VTE). Nowadays, DOACs represent the gold standard for long-term anticoagulation, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit low-intensity apixaban and rivaroxaban are approved for clinical usage as secondary VTE prophylaxis, there are few literature data regarding their efficacy and safety with a long follow-up. Objectives: The aim of our study was to evaluate the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis in patients at high risk of VTE recurrence. Methods: We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily with a follow-up ≥ 12 months. Results: The examined patients were 323. The median low-dose DOAC administration time was 25.40 months (IQR 13.93-45.90). Twelve (3.7%) VTE recurrences were observed; 21 bleeding events were registered (6.5%), including one episode of Major bleeding (MB) (0.3%), 8 Clinically relevant nonmajor bleeding (CRNMB) (2.5%) and 12 minor bleeding (3.7%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between the rivaroxaban and apixaban groups. Patients included in the study for multiple episodes of VTE presented a significantly higher risk of a new VTE recurrence during low-intensity DOAC. Conclusions: Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis in patients at high risk of VTE recurrence; however, attention might be needed in their choice in such a scenario for patients who experienced multiple episodes of VTE.
... Therefore, only weak support for the use of IVIG was given in the recommendation. year [73], and after stopping anticoagulation, VTE recurrence is 3.6% per year [74]. Data from this cohort study suggest that the majority of patients were not on anticoagulation at the time of VTE recurrence or vaccination. ...
... The risk of recurrence is not uniform among patients; it is very high in those with persistent and strong risk factors (such as cancer), high in those with unprovoked events, low when the event is associated with transient and weak risk factors, and very low when it occurs in association with major surgery or other serious clinical conditions [5]. According to a recent systematic review and meta-analysis that included 18 studies and 7515 patients with unprovoked VTE [6], the recurrence rate one year after anticoagulant withdrawal was 10.3%, with a cumulative incidence at 5 years of 25%. These data seem to support prolonged anticoagulation beyond the first 3-6 months in patients with unprovoked VTE, provided that they are not at high risk of bleeding. ...
Background:
Patients with acute venous thromboembolism (VTE) need anticoagulation (AC) therapy for at least 3/6 months (primary treatment); after that period, they should receive a decision on the duration of therapy.
Methods:
This study examined the complications occurring during two years of follow-up (FU) in patients with a first VTE who were recruited in 20 clinical centers and had discontinued or prolonged AC. They were included in the START2-POST-VTE prospective observational study.
Results:
A total of 720 patients (53.5% males) who, after the completion of primary treatment, had received the decision to continue (n = 281, 39%; 76.1% with a DOAC) or discontinue (n = 439, 61%) AC were followed up for 2 years (total FU = 1318 years). The decision to prolong or suspend AC was made in similar proportions in patients with unprovoked or provoked index events. Courses of sulodexide treatment or Aspirin (100 mg daily) were prescribed to 20.3% and 4.5%, respectively, of the patients who discontinued AC. The bleeding rate was significantly higher in patients who extended AC (1.6% pt/y) than in those who stopped AC (0.1% pt/y; p = 0.001) and was higher in patients using standard-dose DOACs (3.1% pt/y) than in those using reduced-dose DOACs (0.4% pt/y). The recurrent VTE rates were similar between the two groups (2.2% pt/y during AC vs. 3% pt/y off AC).
Conclusion:
Physicians' decisions about AC duration were independent of the unprovoked/provoked nature of the index event. The bleeding rate was higher in patients who continued AC using standard-dose DOACs. Surprisingly, the rate of thrombotic recurrence was not different between those who continued or discontinued AC. Randomized studies comparing different procedures to decide on the duration of AC after a first VTE are needed.
... In addition to being frequent and serious, the frequency of negative consequences following VTE are common. The recurrence rates of VTE is reported to be as high as 36% within ten years after an initial event [3][4][5], and between 40 and 60% of patients experience continued symptoms like pain, cramps and swelling of the affected leg in the case of DVT, and shortness of breath, dizziness and fatigue following PE [3,[6][7][8]. Naturally, these sequelae have a substantial impact on the patients' everyday life as impaired physical and mental health may limit their ability to participate in work and social activities [6,[8][9][10][11][12]. ...
Purpose
Most patient-reported outcome (PROs) used in thrombosis research and clinical practice are delivered using technology like online questionnaires. However, only few have undergone formal electronic adaptation from paper to digital versions, threatening the validity and reliability of the PROs. The present study aimed to perform an electronic adaption and cross-cultural translation of two PROs measuring health-related quality of life in a Danish cohort of patients with venous thrombosis (VTE), specifically the VEINES-QoL/Sym questionnaire and the PEmb-QoL questionnaire.
Methods
The electronic adaption and cross-cultural translation processes followed the international guidelines recommended by ISPOR. The migration of the questionnaires from paper to electronic versions was conducted in the Research Electronic Data Capture (REDCap). Following approval of the electronically adapted and translated versions, a pretest of the questionnaires was performed by cognitive interviewing patients with VTE recruited from a hospital setting.
Results
Nine men and ten women between the age of 19 and 73 years participated in cognitive interviews. The questionnaires were successfully adapted from paper to electronic versions, and during the migration process only a few modifications to the content and format were made. Most comments were related to technicalities, e.g. touch functions and checkboxes. The cross-cultural translation of both questionnaires was satisfactory, as only minor rephrasing was required.
Conclusions
The original and Danish version of VEINES-QoL/Sym and PEmb-QoL were successfully adapted into electronic versions and are ready to share for REDCap users. Furthermore, the Danish versions of the two questionnaires have shown satisfactory face validity.
... Risk of recurrent VTE after stopping anticoagulation after unprovoked VTE has been reported as 25% (95% CI, 21%-29%) at 5 years and 36% (95% CI, 28%-45%) at 10 years, with 4% (95% CI, 2%-6%) of events being fatal [6]. In another systematic review examining long-term bleeding risk in patients receiving extended anticoagulation, the incidence of major bleeding per 100 person-years was 1.74 (95% CI, 1.34-2.20) ...
