Aims
Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non‐massive PE, which may inform ...clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non‐massive PE during anticoagulation and after its discontinuation.
Methods and results
We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (<90 mm Hg). We compared the risks of recurrent VTE, major bleeding, and mortality using time‐to‐event multivariable competing risk modeling. There were 3.5% of massive PE among 38 996 patients with PE. During the anticoagulation period, massive PE was associated with a greater risk of major bleeding (subhazard ratio sHR 1.72, 95% confidence interval CI 1.28–2.32), but not of recurrent VTE (sHR 1.15, 95% CI 0.75–1.74) than non‐massive PE. An increased risk of mortality was only observed in the first month after PE. After discontinuation of anticoagulation, among 11 579 patients, massive PE and non‐massive PE had similar risks of mortality, bleeding, and recurrent VTE (sHR 0.85, 95% CI 0.51–1.40), but with different case fatality of recurrent PE (11.1% versus 2.4%, P = .03) and possibly different risk of recurrent fatal PE (sHR 3.65, 95% CI 0.82–16.24).
Conclusion
In this large prospective registry, the baseline hemodynamic status of the incident PE did not influence the risk of recurrent VTE, during and after the anticoagulation periods, but was possibly associated with recurrent PE of greater severity.
While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain ...understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (
P
< 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation.
The optimal cutoff for systolic blood pressure (SBP) level to define high-risk pulmonary embolism (PE) remains to be defined.
To evaluate the relationship between SBP levels on admission and ...mortality in patients with acute symptomatic PE, the current study included 39,257 consecutive patients with acute symptomatic PE from the RIETE registry between 2001 and 2018. Primary outcomes included all-cause and PE-specific 30-day mortality. Secondary outcomes included major bleeding and recurrent venous thromboembolism (VTE).
There was a linear inverse relationship between admission SBP and 30-day all-cause and PE-related mortality that persisted after multivariable adjustment. Patients in the lower SBP strata had higher rates of all-cause death (reference: SBP 110–129 mmHg) (adjusted odds ratio OR 2.9; 95% confidence interval CI, 2.0–4.2 for SBP <70 mmHg; and OR 1.7; 95% CI, 1.4–2.1 for SBP 70–89 mmHg). The findings for 30-day PE-related mortality were similar (adjusted OR 4.4; 95% CI, 2.7–7.2 for SBP <70 mmHg; and OR 2.6; 95% CI, 1.9–3.4 for SBP 70–89 mmHg). Patients in the higher strata of SBP had significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR 0.7; 95% CI, 0.5–0.9 for SBP 170–190 mmHg; and OR 0.6; 95% CI, 0.4–0.9 for SBP >190 mmHg). Consistent findings were also observed for 30-day PE-related death.
In patients with acute symptomatic PE, a low SBP portends an increased risk of all-cause and PE-related mortality. The highest mortality was observed in patients with SBP <70 mmHg.
•The optimal cutoff for systolic blood pressure (SBP) level to define high-risk pulmonary embolism (PE) remains to be defined.•There is a linear inverse relationship between admission SBP and 30-day all-cause and PE-related mortality.•The highest mortality is observed in patients with SBP <70 mmHg.
•Deep vein thrombosis (DVT) is associated with mortality in pulmonary embolism (PE).•The impact of DVT symptoms in patients with acute PE and lower-limb DVT is unknown.•Patients with DVT symptoms had ...a higher 30-day all-cause and PE-related mortality.•Assessment of DVT symptoms would assist with risk stratification of these patients.•Tests to detect lower-limb DVT in PE patients with DVT symptoms would be justified.
In patients with acute symptomatic pulmonary embolism (PE), the presence of concomitant lower-limb deep vein thrombosis (DVT) has been associated with a higher mortality rate. The prognostic significance of DVT symptoms among these patients remains uncertain.
We used the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 30-day mortality rate in patients with PE and concomitant lower-limb DVT, according to the presence or absence of DVT symptoms. Primary outcomes were all-cause death and PE-related death within the first 30 days.
Since March 2001 to June 2021, there were 17,742 patients with acute symptomatic PE and objectively proven concomitant lower-limb DVT. Of these, 11,984 (68%) had DVT symptoms. Most patients with or without DVT symptoms (82% vs. 81%) received low-molecular-weight heparin initially. Then, most (61% vs. 58%) switched to vitamin K antagonists. During the first 30 days of therapy, 497 patients with DVT symptoms (4.1%) and 164 (2.8%) with no DVT symptoms died (rate ratio RR: 1.48; 95%CI: 1.23-1.77). The rates of PE-related death were: 1.0% vs. 0.7%, respectively (RR: 1.50; 95%CI: 1.04-2.16). On multivariable analysis, patients with DVT symptoms were at increased risk for all-cause death (adjusted hazard ratio aHR: 1.49; 95%CI: 1.24-1.78), and PE-related death (aHR: 1.52; 95%CI: 1.05-2.20).
Among patients with acute symptomatic PE and concomitant lower-limb DVT, those with DVT symptoms had an increased all-cause and PE-related mortality within 30 days. Assessment of DVT symptoms would assist with risk stratification of these patients.
Background A comprehensive evaluation of temporal trends in the treatment of patients who have DVT may assist with identification of modifiable factors that contribute to short-term outcomes. Methods ...We assessed temporal trends in length of hospital stay and use of pharmacological and interventional therapies among 26,695 adults with DVT enrolled in the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2014. We also examined temporal trends in risk-adjusted rates of all-cause, pulmonary embolism-related, and bleeding-related death to 30 days after diagnosis. Results The mean length of hospital stay decreased from 9.0 days in 2001 to 2005 to 7.6 days in 2010 to 2014 ( P < .01). For initial DVT treatment, the use of low-molecular-weight heparin decreased from 98% to 90% ( P < .01). Direct oral anticoagulants use increased from 0.5% in 2010 to 13.4% in 2014 ( P < .001). Risk-adjusted rates of 30-day all-cause mortality decreased from 3.9% in 2001 to 2005 to 2.7% in 2010 to 2014 (adjusted rate ratio per year, 0.84; 95% CI, 0.74-0.96; P < .01). VTE-related mortality showed a nonstatistically significant downward trend (adjusted rate ratio per year, 0.70; 95% CI, 0.44-1.10; P = .13), whereas 30-day bleeding-related mortality significantly decreased from 0.5% in 2001 to 2005 to 0.1% in 2010-2014 (adjusted rate ratio per year, 0.55; 95% CI, 0.40-0.77; P < .01). Conclusions This international registry-based temporal analysis identified reductions in length of stay for adults hospitalized for DVT. The study also found a decreasing trend in adjusted rates of all-cause and bleeding-related mortality.
Background Transthoracic echocardiography ( TTE ) is often considered for risk stratification of patients with acute pulmonary embolism ( PE ). We sought to determine the contemporary utilization of ...early TTE (within 72 hours of PE diagnosis) and explored the association between TTE findings and PE -related mortality. Methods and Results Data from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry, a multicenter registry of consecutive patients with acute PE , were used (2001-July 2017). We used a generalized linear mixed model to determine predictors of early TTE performance. Moreover, the association between 3 TTE variables (right atrial enlargement, right ventricular hypokinesis, and presence of right heart thrombi) and 30-day PE -related mortality was assessed in generalized linear mixed models adjusted for PE severity index, and other comorbidities. Among 35 935 enrollees with acute PE , 15 375 (42.8%) underwent early TTE . There was an increase in early TTE utilization rate over time ( P<0.001 for trend). Younger age, female sex, enrollment in countries other than Spain, history of coronary disease, heart failure, atrial fibrillation, tachycardia, and hypotension were the main predictors of early TTE ( P<0.01 for all). In multivariable analyses, right atrial enlargement (adjusted odds ratio: 3.74; 95% confidence interval, 2.10-6.66), right ventricular hypokinesis (adjusted odds ratio: 3.11, 95% confidence interval: 1.85-5.21) and right heart thrombi (adjusted odds ratio: 4.39, 95% confidence interval, 1.99-9.71) were associated with increased odds for PE -related mortality. Conclusions Early TTE is commonly performed for acute PE and utilization rates have increased over time. Right atrial enlargement, right ventricular hypokinesis, and right heart thrombi are predictive of worse outcomes. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02832245.
Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins ...without proximal extension or pulmonary embolism (PE).
To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT.
This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection.
Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE.
A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean SD age, 61 17 years; 2975 male patients 50.1%), and 27 959 (82.5%) had proximal DVT (mean SD age, 65 18 years; 14 315 male patients 51.2%). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio OR, 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio HR, 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%).
Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.
The choice of the imaging modality for diagnosis of pulmonary embolism (PE) could be influenced by provider, patient or hospital characteristics, or over time. However, little is known about the ...choice of the diagnostic modalities in practice. The aim of this study was to evaluate the variations in the use of imaging modalities for patients with acute PE.
Using the data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective international registry of patients with venous thromboembolism (March 2001-January 2019), we explored the imaging modalities used in patients with acute PE. The imaging modalities included computed tomography pulmonary angiography, ventilation/perfusion scanning, pulmonary angiography, a combination of these tests, or PE signs and symptoms plus imaging-confirmed proximal deep vein thrombosis but no chest imaging.
Among 38 025 patients with confirmed PE (53.1% female, age: 67.3±17 years), computed tomography pulmonary angiography was the dominant modality of diagnosis in all RIETE enrollees (78.2% 99% CI, 77.6-78.7); including pregnant patients (58.9% 99% CI, 47.7%-69.4%) and patients with severe renal insufficiency (62.5% 99% CI, 59.9-65.0). A greater proportion of patients underwent ventilation/perfusion scanning in larger hospitals compared with smaller hospitals (13.1% versus 7.3%,
<0.001). The use of computed tomography pulmonary angiography varied between 13.3% and 98.3% across the countries, and its use increased over time (46.5% in 2002 to 91.7% in 2018,
<0.001).
In a large multinational PE registry, variations were observed in the use of imaging modalities according to patient or institutional factors and over time. However, computed tomography pulmonary angiography was the dominant modality of diagnosis, even in pregnancy and severe renal insufficiency. The safety, costs, and downstream effects of these tests on PE-related and non-PE-related outcomes warrant further investigation.
Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE).
We used the data ...in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT).
Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE.
During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis.
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