Fatal recurrent VTE after anticoagulant treatment for unprovoked VTE: a systematic review

Current guidelines recommend long-term anticoagulant therapy in patients with unprovoked venous thromboembolism (VTE). The risk of fatal recurrent VTE after treatment discontinuation (versus that of fatal bleeding during anticoagulation) is of particular relevance in the decision to continue or stop anticoagulation after the first 3 months. Our primary aim was to provide a point-estimate of the yearly rate of fatal recurrent VTE and VTE case-fatality rate in patients with unprovoked VTE after anticoagulation cessation. Data were extracted from both randomised controlled trials and observational studies published before May 1, 2017. The pooled fatality rates were calculated using a random-effects model. 18 studies with low-to-moderate bias were included in the primary analysis, totalling 6758 patients with a median (range) follow-up duration of 2.2 (1-5) years. After anticoagulation cessation, the weighted pooled rate of VTE recurrence was 6.3 (95% CI 5.4-7.3) per 100 patient-years and the weighted pooled rate of fatal recurrent VTE was 0.17 (95% CI 0.047-0.33) per 100 patient-years, for a case-fatality rate of 2.6% (95% CI 0.86-5.0). These numbers are a solid benchmark for comparison to the risks associated with long-term anticoagulation treatment for the decision on the optimal duration of treatment of patients with unprovoked VTE

Lower prevalence of subsegmental pulmonary embolism after application of the YEARS diagnostic algorithm

The rate of identified isolated subsegmental pulmonary embolism (ssPE) has doubled with advances in computed tomography pulmonary angiography (CTPA) technology, but its clinical relevance is debated. The YEARS diagnostic algorithm was shown to safely reduce the number of required CTPAs in the diagnostic management of PE. We hypothesized that the higher threshold for performing CTPA in YEARS was associated with a lower prevalence of ssPE compared to the conventional diagnostic algorithm. We compared 2291 consecutive patients with suspected PE managed according to YEARS to 3306 consecutive control patients managed according to the Wells score for the prevalence of isolated ssPE. In the YEARS cohort, 52% were managed without CTPA, 12% had pulmonary embolism (PE) of which 10% were isolated ssPE, and the 3-month diagnostic failure rate was 0·35%. In the control cohort, 32% were managed without CTPA, 20% had PE of which 16% were isolated ssPE, and the 3-month failure rate was 0·73%. The isolated ssPE prevalence was significantly lower in YEARS (absolute difference 6·2% (95% confidence interval [CI] 1·4–10), Odds Ratio 0·58 (95% CI 0·37–0·90). In conclusion, YEARS is associated with a lower prevalence of isolated ssPE, due to reduction in CTPAs by the higher D-dimer threshold. This was however not associated with a higher risk of recurrent VTE during follow-up

Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism

Acute pulmonary embolism is one of the leading causes of maternal death, with the overall incidence reported to be 1.72 cases per 1000 deliveries, accounting for approximately 1 death in every 100,000 deliveries. Since the D-dimer test has low specificity and sensitivity, it is common for pregnant women with suspected pulmonary embolism to undergo computed tomography (CT) pulmonary angiography or ventilation-perfusion (V/Q) scanning, both of which involve radiation exposure to the mother and fetus. It is unknown whether a pregnancy-adapted clinical screening algorithm could be used to safely avoid diagnostic imaging in a subset of pregnant women with suspected pulmonary embolism. The researchers performed a multicenter, international, prospective study of pregnant women with suspected pulmonary embolism. They assessed 3 criteria from the YEARS algorithm (clinical signs of deep vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the D-dimer level as components of the screening algorithm. Pulmonary embolism was ruled out if none of the 3 criteria were met and the D-dimer level was less than 1000 ng/mL, or if 1 or more of the 3 criteria were met and the D-dimer level was less than 500 ng/mL. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep vein thrombosis; if the results were positive (ie, a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out by screening criteria underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism (VTE) at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval, 0.0%–1.2%); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% confidence interval, 35%–44%). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. The researchers concluded that the pregnancy-adapted YEARS diagnostic algorithm safely ruled out acute pulmonary embolism in pregnant patients who were referred for suspected pulmonary embolism. Using this approach, they found that the main advantage was that CT pulmonary angiography was averted in 32% to 65% of the patients, depending on the trimester of presentation, without compromising safety

Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study

Validated diagnostic algorithms in patients with suspected pulmonary embolism are often not used correctly or only benefit subgroups of patients, leading to overuse of computed tomography pulmonary angiography (CTPA). The YEARS clinical decision rule that incorporates differential D-dimer cutoff values at presentation, has been developed to be fast, to be compatible with clinical practice, and to reduce the number of CTPA investigations in all age groups. We aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism. We did a prospective, multicentre, cohort study in 12 hospitals in the Netherlands, including consecutive patients with suspected pulmonary embolism between Oct 5, 2013, to July 9, 2015. Patients were managed by simultaneous assessment of the YEARS clinical decision rule, consisting of three items (clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis), and D-dimer concentrations. In patients without YEARS items and D-dimer less than 1000 ng/mL, or in patients with one or more YEARS items and D-dimer less than 500 ng/mL, pulmonary embolism was considered excluded. All other patients had CTPA. The primary outcome was the number of independently adjudicated events of venous thromboembolism during 3 months of follow-up after pulmonary embolism was excluded, and the secondary outcome was the number of required CTPA compared with the Wells' diagnostic algorithm. For the primary outcome regarding the safety of the diagnostic strategy, we used a per-protocol approach. For the secondary outcome regarding the efficiency of the diagnostic strategy, we used an intention-to-diagnose approach. This trial is registered with the Netherlands Trial Registry, number NTR4193. 3616 consecutive patients with clinically suspected pulmonary embolism were screened, of whom 151 (4%) were excluded. The remaining 3465 patients were assessed of whom 456 (13%) were diagnosed with pulmonary embolism at baseline. Of the 2946 patients (85%) in whom pulmonary embolism was ruled out at baseline and remained untreated, 18 patients were diagnosed with symptomatic venous thromboembolism during 3-month follow-up (0·61%, 95% CI 0·36-0·96) of whom six had fatal pulmonary embolism (0·20%, 0·07-0·44). CTPA was not indicated in 1651 (48%) patients with the YEARS algorithm compared with 1174 (34%) patients, if Wells' rule and fixed D-dimer threshold of less than 500 ng/mL would have been applied, a difference of 14% (95% CI 12-16). In our study pulmonary embolism was safely excluded by the YEARS diagnostic algorithm in patients with suspected pulmonary embolism. The main advantage of the YEARS algorithm in our patients is the absolute 14% decrease of CTPA examinations in all ages and across several relevant subgroups. This study was supported by unrestricted grants from the participating hospital

Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data

BACKGROUND: Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. OBJECTIVES: The aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis. METHODS: We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided. RESULTS: We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127). CONCLUSION: This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis

Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data.

BACKGROUND Few studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. OBJECTIVES The aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis. METHODS We performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided. RESULTS We identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127). CONCLUSION This study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis

Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism

BACKGROUND: Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. METHODS: In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. RESULTS: A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval [CI], 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. CONCLUSIONS: Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients