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Papers by Manuel Monreal

Research paper thumbnail of Presenting Characteristics, Treatment Patterns, and Outcomes among Patients with Venous Thromboembolism during Hospitalization for COVID-19

Seminars in Thrombosis and Hemostasis

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). Howe... more Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55–74) years. Most patients (68%) w...

Research paper thumbnail of Association of Inferior Vena Cava Filter Use With Mortality Rates in Older Adults With Acute Pulmonary Embolism

JAMA Internal Medicine

Acute pulmonary embolism (PE) is a common cause of morbidity and mortality in older adults. 1 Inf... more Acute pulmonary embolism (PE) is a common cause of morbidity and mortality in older adults. 1 Inferior vena cava (IVC) filters are frequently used to prevent subsequent PE; nearly 1 in 6 of elderly Medicare fee-for-service (FFS) beneficiaries with PE received an IVC filter. 2 However, the evidence supporting device efficacy and safety is scant. 3 In recent years, the US Food and Drug Administration raised concerns about the safety of IVC filters, and some studies have indicated a temporal decrease in the use of this technology. 4 Meanwhile, some investigators, using administrative data with limited adjustments, have found that the use of IVC filters was associated with reduced mortality rates, recommending their use. 5 This study sought to determine the association between use of IVC filters and mortality rates in Medicare FFS beneficiaries with PE using 3 distinct statistical approaches.

Research paper thumbnail of Meta-Analysis of Prevalence and Short-Term Prognosis of Hemodynamically Unstable Patients With Symptomatic Acute Pulmonary Embolism

The American Journal of Cardiology

There remains limited information about the prevalence and outcomes of hemodynamic unstable patie... more There remains limited information about the prevalence and outcomes of hemodynamic unstable patients with acute pulmonary embolism (PE). We performed a systematic review and meta-analysis of prospective registries that enrolled patients with acute PE to assess the prevalence and prognostic significance of hemodynamic instability for the primary outcome of short-term all-cause mortality, and the secondary outcome of short-term PE-related mortality. We also assessed the association between use of thrombolytic therapy versus no use and short-term outcomes in the subgroup of unstable patients. We used a random-effects model to pool study results; and I testing to assess for heterogeneity. The authors' search retrieved 4 studies that enrolled 1,574 patients with unstable PE (1,574/40,363; 3.9%; 95% confidence interval [CI], 3.7% to 4.1%). Hemodynamic instability had a significant association with short-term all-cause mortality (odds ratio [OR], 5.9; 95% CI, 2.7 to 13.0; I = 94%), and with PE-related death (OR, 8.2; 95% CI, 3.4 to 19.7). In unstable patients, thrombolytic therapy was associated with reduced odds of short-term all-cause mortality (OR, 0.69; 95% CI, 0.49 to 0.95), and PE-related death (OR, 0.66; 95% CI, 0.45 to 0.97). In conclusion, hemodynamic instability significantly increased the risk of death shortly after PE diagnosis. Use of thrombolytic therapy was associated with significantly reduced short-term mortality.

Research paper thumbnail of Apixaban for Treating Venous Thromboembolism in Real-World Clinical Practice

Thrombosis and Haemostasis

Research paper thumbnail of Early Use of Echocardiography in Patients With Acute Pulmonary Embolism: Findings From the RIETE Registry

Journal of the American Heart Association, Jan 4, 2018

Background Transthoracic echocardiography ( TTE ) is often considered for risk stratification of ... more 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 ...

Research paper thumbnail of The impact of co-morbidity on the disease burden of VTE

Journal of thrombosis and thrombolysis, Jan 14, 2018

Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confoun... more Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confound data interpretation concerning VTE-related mortality, costs and quality of life. We aimed to assess the contribution of co-morbidities to the burden of VTE. The PREFER in VTE registry, across seven European countries, documented and followed acute VTE patients over 12 months. Patients with co-morbidities were grouped in major co-morbidity groups: cancer, cardiovascular (CV) comorbidity (other than VTE), CV risks, venous, renal, liver, respiratory, bone and joint diseases, and lower extremity paralysis. Mortality rates and health-related quality of life (HrQoL) utility values grouped per co-morbidity were compared to the UK general population. Regression analyses were performed to determine the impact of co-morbidities on mortality and HrQoL. VTE were analyzed together and separately as pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 3455 patients were included, 40.5% ...

Research paper thumbnail of Pulmonary embolism in Europe - Burden of illness in relationship to healthcare resource utilization and return to work

Thrombosis research, Oct 16, 2018

Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from p... more Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from patients in Europe is scarce. The aim of this study was to report the impacts of PE on healthcare resource utilization (HCRU) and return to work using the PREFER in VTE registry. The PREFER in VTE registry was a prospective, observational, multicenter study in seven European countries, aiming to provide data concerning treatment patterns, HCRU, mortality, quality of life and work-loss. Patients with a first-time or recurrent PE were included and followed up at 1, 3, 6 and 12 months. Treatment patterns, re-hospitalization rates, length of hospital stays (LOS), and ambulatory/office visits, as well as proportion of patients returning to work, were assessed. Subgroups by country and with/without active cancer were examined separately. Zero-inflated negative binomial and Cox regression were applied to investigate the relationship between baseline characteristics and LOS and return to work, re...

Research paper thumbnail of Thirty-day outcomes in patients with acute pulmonary embolism who discontinued anticoagulant therapy before 90 days

American heart journal, Jan 5, 2018

The contemporary natural history of patients with acute pulmonary embolism (PE) not receiving (or... more The contemporary natural history of patients with acute pulmonary embolism (PE) not receiving (or early discontinuing) anticoagulant therapy has not been consistently evaluated. To assess the rate of the composite outcome of PE-related death, sudden death, or recurrent thromboembolism (VTE) within 30 days in all PE patients in whom anticoagulation was not administered or discontinued prematurely (<90 days of anticoagulation). We used the RIETE database to assess the incidence rates (per 100 person-days) of the composite outcome within the subsequent 30 days. The risk of these events was compared to PE patients who were anticoagulated for ≥90 days. Of 34,447 PE recruited from 2001 to 2017, 47 (0.14%) did not receive anticoagulants and 1348 (3.91%) discontinued it before 90 days. Fatal PE developed in 25 (53%) of those without any anticoagulation and in 45 (3.33%) with premature discontinuations. Sudden death or non-fatal recurrent VTE occurred in 6 (0.45%) and 24 (1.48%) patients,...

Research paper thumbnail of Epidemiology, patterns of care and mortality for patients with hemodynamically unstable acute symptomatic pulmonary embolism

International journal of cardiology, Jan 16, 2018

Limited information exists about the epidemiology, management and outcomes of hemodynamically uns... more Limited information exists about the epidemiology, management and outcomes of hemodynamically unstable patients with acute pulmonary embolism (PE). We aimed to evaluate the prevalence and outcomes of unstable PE, and to assess the acute management in routine clinical practice. This study included 34,380 patients from the RIETE registry with PE between 2001 and 2016. Primary outcomes included all-cause and PE-specific 30-day mortality. We used multivariable adjustments to calculate hazard ratios among unstable patients who did and did not receive reperfusion. Overall, 1207 patients (3.5%) presented with hemodynamic instability. All-cause 30-day mortality was 14% and 5.4% in those with versus those without hemodynamic instability (P < 0.001). Two hundred and thirty eight (20%) unstable patients received reperfusion therapy. After multivariable adjustment, reperfusion therapy was associated with non-significantly reduced 30-day all-cause mortality (hazard ratio [HR] 0.71; 95% CI, 0....

Research paper thumbnail of Clinical Course of Venous Thromboembolism in Patients with Pancreatic Cancer: Insights from the RIETE Registry

Thrombosis and haemostasis, 2018

Research paper thumbnail of Lipoprotein (a) levels and outcomes in stable outpatients with symptomatic artery disease

Atherosclerosis, Jan 4, 2018

Although genetic and epidemiological studies support that people with high lipoprotein (a) [Lp(a)... more Although genetic and epidemiological studies support that people with high lipoprotein (a) [Lp(a)] levels are at an increased risk for arterial disease, its prognostic value in patients with established artery disease has not been consistently evaluated. FRENA is a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We assessed the risk for subsequent myocardial infarction, ischemic stroke or limb amputation according to Lp(a) levels at baseline. As of December 2016, 1503 stable outpatients were recruited. Of these, 814 (54%) had levels <30 mg/dL, 319 (21%) had 30-50 mg/dL and 370 (25%) had ≥50 mg/dL. Over a mean follow-up of 36 months, 294 patients developed subsequent events (myocardial infarction 122, ischemic stroke 114, limb amputation 58) and 85 died. On multivariable analysis, patients with Lp(a) levels of 30-50 mg/dL were at a higher risk for myocardial infarction (hazard ratio [HR]: 4.67; 95%CI: 2.77-7.85), ischemi...

Research paper thumbnail of Long-term outcomes of isolated superficial vein thrombosis in patients with active cancer

Thrombosis research, Jan 20, 2018

Cancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at high... more Cancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at higher risk of death than similar cancer patients who do not develop DVT or PE. The impact of isolated superficial venous thrombosis (SVT) (i.e. without DVT or PE) on the prognosis of cancer patients is unknown. Data from the OPTIMEV, multicentre, observational study, to compare at 3 years the incidences of death, DVT-PE recurrence and bleeding of cancer patients with objectively confirmed SVT vs. cancer patients with DVT (matched 1:2 on age, sex, cancer stage) and vs. patients with SVT without cancer (matched 1:3 on age and sex). Cancer patients with SVT (n = 34) had a high risk of death (23.2%patient-year(PY)), that was similar to that of cancer patients with DVT (aHR = 1.0[0.6-1.9]) and higher to that of SVT patients without cancer (aHR = 9.0[3.5-23.1]). Cancer patients with SVT received anticoagulants for a median duration of 45 days and had a high risk of DVT-PE recurrence (6.0%PY), sim...

Research paper thumbnail of Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism

The American journal of medicine, Jan 25, 2018

Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patie... more Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism has been also established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined. The current study analyzed clinical characteristics, time-course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5,717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism). During anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 ...

Research paper thumbnail of Performance of Early Prognostic Assessment Independently Predicts the Outcomes in Patients with Acute Pulmonary Embolism

Thrombosis and haemostasis, 2018

Research paper thumbnail of Validation of a prognostic score for hidden cancer in unprovoked venous thromboembolism

PloS one, 2018

The usefulness of a diagnostic workup for occult cancer in patients with venous thromboembolism (... more The usefulness of a diagnostic workup for occult cancer in patients with venous thromboembolism (VTE) is controversial. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to perform a nested case-control study to validate a prognostic score that identifies patients with unprovoked VTE at increased risk for cancer. We dichotomized patients as having low- (≤2 points) or high (≥3 points) risk for cancer, and tried to validate the score at 12 and 24 months. From January 2014 to October 2016, 11,695 VTE patients were recruited. Of these, 1,360 with unprovoked VTE (11.6%) were eligible for the study. At 12 months, 52 patients (3.8%; 95%CI: 2.9-5%) were diagnosed with cancer. Among 905 patients (67%) scoring ≤2 points, 22 (2.4%) had cancer. Among 455 scoring ≥3 points, 30 (6.6%) had cancer (hazard ratio 2.8; 95%CI 1.6-5; p<0.01). C-statistic was 0.63 (95%CI 0.55-0.71). At 24 months, 58 patients (4.3%; 95%CI: 3.3-5.5%) were diagnosed with cancer. Among 905 pat...

Research paper thumbnail of Systematic review of efficacy and safety of retrievable inferior vena caval filters

Thrombosis research, May 1, 2018

Inferior vena caval (IVC) filters are used with the premise of preventing pulmonary embolism (PE)... more Inferior vena caval (IVC) filters are used with the premise of preventing pulmonary embolism (PE). Concerns for complications due to longstanding dwell time led to development of retrievable filters, which were cleared by the Food and Drug Administration (FDA) in early 2000’s. This temporally correlated with permissive recommendations for use in several clinical scenarios1 and frequent utilization of IVC filters. Among Medicare Fee-For-Service beneficiaries with PE, one in every 6 received an IVC filter.2 Yet, overall evidence for efficacy of IVC filters remains limited.3,4 Further, some retrievable filters possess distinct features that may impact their efficacy and safety. At one hand, such features are presumably advantageous making them amenable to removal (e.g. when a patient no longer has contraindication to anticoagulation). However, alternative anchoring mechanisms may make these filters susceptible to tilting (with potential to reduce retrievability, but also to reduce efficacy), migration, perforation, and injury to adjacent organs. 5,6 We performed a systematic review of the prospective controlled studies to determine the efficacy and safety of retrievable IVC filters.

Research paper thumbnail of Management appropriateness and outcomes of patients with acute pulmonary embolism

The European respiratory journal, 2018

The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary ... more The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary embolism (PE) has not been well defined by previous studies.In this prospective cohort study of patients admitted to a respiratory department (n=2096), we evaluated whether patients with PE had better outcomes if they were acutely managed according to international guidelines. Outcomes consisted of all-cause mortality, PE-related mortality, recurrent venous thromboembolism (VTE) and major bleeding events during the first month of follow-up after diagnosis.Overall, 408 patients (19% (95% CI 18-21%)) did not receive guideline-adherent PE management. Patients receiving non-adherent management were significantly more likely to experience all-cause mortality (adjusted odds ratio (OR) 2.39 (95% CI 1.57-3.61) or PE-related mortality (adjusted OR 5.02 (95% CI 2.42-10.42); p<0.001) during follow-up. Non-adherent management was also a significant independent predictor of recurrent VTE (OR 2.19 ...

Research paper thumbnail of Impact of Thrombus Sidedness on Presentation and Outcomes of Patients with Proximal Lower Extremity Deep Vein Thrombosis

Seminars in thrombosis and hemostasis, Jan 12, 2018

Small studies have suggested differences in demographics and outcomes between left- and right-sid... more Small studies have suggested differences in demographics and outcomes between left- and right-sided deep vein thrombosis (DVT), and also unilateral versus bilateral DVT. We investigated the clinical presentation and outcomes of patients with DVT based on thrombus sidedness. The authors used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) database (2001-2016) to identify patients with symptomatic proximal lower-extremity DVT. Main outcomes included cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality. Overall, 30,445 patients were included. The majority of DVTs occurred in the left leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; < 0.001 for chi-squared test comparing all three groups). Comorbidities were relatively similar in those with left-sided and right-sided DVT. Compared with those with left-sided DVT, patients with right-sided DVT had higher relative frequency of PE (26% versus 23%, < 0.001) and 1-year mor...

Research paper thumbnail of Predictors of Post-Thrombotic Ulcer after Acute DVT: The RIETE Registry

Thrombosis and haemostasis, 2018

In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is the most debilita... more In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is the most debilitating and end-stage clinical expression of the post-thrombotic syndrome (PTS). To date, risk factors for PTS-related ulcer in DVT patients have not been identified.We used the international observational RIETE registry to assess the evolution of PTS signs and symptoms during a 3-year follow-up period and to identify independent predictors of PTS ulcer at 1 year in patients with acute DVT.Among 1,866 eligible patients, cumulative rates of PTS ulcer at 1, 2 and 3 years were 2.7% ( = 50), 4.3% ( = 54) and 7.1% ( = 60), respectively. The proportion of patients with PTS symptoms at 1, 2 or 3 years remained stable (≈40%), while the proportion of patients with PTS signs increased slightly over time (from 49 to 53%). Prior history of venous thromboembolism (VTE) (odds ratio [OR] = 5.5 [2.8-10.9]), diabetes (OR = 2.3 [1.1-4.7]), pre-existing leg varicosities (OR = 3.2 [1.7-6.1]) and male sex (OR =...

Research paper thumbnail of Anticoagulant therapy for venous thromboembolism in patients with inflammatory bowel disease

European journal of gastroenterology & hepatology, Jan 16, 2018

There is lack of evidence to guide the type, intensity, and the duration of anticoagulation follo... more There is lack of evidence to guide the type, intensity, and the duration of anticoagulation following venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD). Registro Informatizado Enfermedad Trombo Embólica (RIETE) is an ongoing, multicenter, observational registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We used the RIETE database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in noncancer patients with or without IBD. As of October 2014, 41 927 patients without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation was similar in patients with VTE during an acute flare (8.3±8.8 months), in remission (9.4±11.5 months), or without IBD (10.0±12.8 months). The rate of VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI: 3.23-19.2; and 5.85, 95% CI: 5.46-6.2...

Research paper thumbnail of Presenting Characteristics, Treatment Patterns, and Outcomes among Patients with Venous Thromboembolism during Hospitalization for COVID-19

Seminars in Thrombosis and Hemostasis

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). Howe... more Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55–74) years. Most patients (68%) w...

Research paper thumbnail of Association of Inferior Vena Cava Filter Use With Mortality Rates in Older Adults With Acute Pulmonary Embolism

JAMA Internal Medicine

Acute pulmonary embolism (PE) is a common cause of morbidity and mortality in older adults. 1 Inf... more Acute pulmonary embolism (PE) is a common cause of morbidity and mortality in older adults. 1 Inferior vena cava (IVC) filters are frequently used to prevent subsequent PE; nearly 1 in 6 of elderly Medicare fee-for-service (FFS) beneficiaries with PE received an IVC filter. 2 However, the evidence supporting device efficacy and safety is scant. 3 In recent years, the US Food and Drug Administration raised concerns about the safety of IVC filters, and some studies have indicated a temporal decrease in the use of this technology. 4 Meanwhile, some investigators, using administrative data with limited adjustments, have found that the use of IVC filters was associated with reduced mortality rates, recommending their use. 5 This study sought to determine the association between use of IVC filters and mortality rates in Medicare FFS beneficiaries with PE using 3 distinct statistical approaches.

Research paper thumbnail of Meta-Analysis of Prevalence and Short-Term Prognosis of Hemodynamically Unstable Patients With Symptomatic Acute Pulmonary Embolism

The American Journal of Cardiology

There remains limited information about the prevalence and outcomes of hemodynamic unstable patie... more There remains limited information about the prevalence and outcomes of hemodynamic unstable patients with acute pulmonary embolism (PE). We performed a systematic review and meta-analysis of prospective registries that enrolled patients with acute PE to assess the prevalence and prognostic significance of hemodynamic instability for the primary outcome of short-term all-cause mortality, and the secondary outcome of short-term PE-related mortality. We also assessed the association between use of thrombolytic therapy versus no use and short-term outcomes in the subgroup of unstable patients. We used a random-effects model to pool study results; and I testing to assess for heterogeneity. The authors&amp;amp;amp;amp;#39; search retrieved 4 studies that enrolled 1,574 patients with unstable PE (1,574/40,363; 3.9%; 95% confidence interval [CI], 3.7% to 4.1%). Hemodynamic instability had a significant association with short-term all-cause mortality (odds ratio [OR], 5.9; 95% CI, 2.7 to 13.0; I = 94%), and with PE-related death (OR, 8.2; 95% CI, 3.4 to 19.7). In unstable patients, thrombolytic therapy was associated with reduced odds of short-term all-cause mortality (OR, 0.69; 95% CI, 0.49 to 0.95), and PE-related death (OR, 0.66; 95% CI, 0.45 to 0.97). In conclusion, hemodynamic instability significantly increased the risk of death shortly after PE diagnosis. Use of thrombolytic therapy was associated with significantly reduced short-term mortality.

Research paper thumbnail of Apixaban for Treating Venous Thromboembolism in Real-World Clinical Practice

Thrombosis and Haemostasis

Research paper thumbnail of Early Use of Echocardiography in Patients With Acute Pulmonary Embolism: Findings From the RIETE Registry

Journal of the American Heart Association, Jan 4, 2018

Background Transthoracic echocardiography ( TTE ) is often considered for risk stratification of ... more 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 ...

Research paper thumbnail of The impact of co-morbidity on the disease burden of VTE

Journal of thrombosis and thrombolysis, Jan 14, 2018

Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confoun... more Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confound data interpretation concerning VTE-related mortality, costs and quality of life. We aimed to assess the contribution of co-morbidities to the burden of VTE. The PREFER in VTE registry, across seven European countries, documented and followed acute VTE patients over 12 months. Patients with co-morbidities were grouped in major co-morbidity groups: cancer, cardiovascular (CV) comorbidity (other than VTE), CV risks, venous, renal, liver, respiratory, bone and joint diseases, and lower extremity paralysis. Mortality rates and health-related quality of life (HrQoL) utility values grouped per co-morbidity were compared to the UK general population. Regression analyses were performed to determine the impact of co-morbidities on mortality and HrQoL. VTE were analyzed together and separately as pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 3455 patients were included, 40.5% ...

Research paper thumbnail of Pulmonary embolism in Europe - Burden of illness in relationship to healthcare resource utilization and return to work

Thrombosis research, Oct 16, 2018

Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from p... more Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from patients in Europe is scarce. The aim of this study was to report the impacts of PE on healthcare resource utilization (HCRU) and return to work using the PREFER in VTE registry. The PREFER in VTE registry was a prospective, observational, multicenter study in seven European countries, aiming to provide data concerning treatment patterns, HCRU, mortality, quality of life and work-loss. Patients with a first-time or recurrent PE were included and followed up at 1, 3, 6 and 12 months. Treatment patterns, re-hospitalization rates, length of hospital stays (LOS), and ambulatory/office visits, as well as proportion of patients returning to work, were assessed. Subgroups by country and with/without active cancer were examined separately. Zero-inflated negative binomial and Cox regression were applied to investigate the relationship between baseline characteristics and LOS and return to work, re...

Research paper thumbnail of Thirty-day outcomes in patients with acute pulmonary embolism who discontinued anticoagulant therapy before 90 days

American heart journal, Jan 5, 2018

The contemporary natural history of patients with acute pulmonary embolism (PE) not receiving (or... more The contemporary natural history of patients with acute pulmonary embolism (PE) not receiving (or early discontinuing) anticoagulant therapy has not been consistently evaluated. To assess the rate of the composite outcome of PE-related death, sudden death, or recurrent thromboembolism (VTE) within 30 days in all PE patients in whom anticoagulation was not administered or discontinued prematurely (<90 days of anticoagulation). We used the RIETE database to assess the incidence rates (per 100 person-days) of the composite outcome within the subsequent 30 days. The risk of these events was compared to PE patients who were anticoagulated for ≥90 days. Of 34,447 PE recruited from 2001 to 2017, 47 (0.14%) did not receive anticoagulants and 1348 (3.91%) discontinued it before 90 days. Fatal PE developed in 25 (53%) of those without any anticoagulation and in 45 (3.33%) with premature discontinuations. Sudden death or non-fatal recurrent VTE occurred in 6 (0.45%) and 24 (1.48%) patients,...

Research paper thumbnail of Epidemiology, patterns of care and mortality for patients with hemodynamically unstable acute symptomatic pulmonary embolism

International journal of cardiology, Jan 16, 2018

Limited information exists about the epidemiology, management and outcomes of hemodynamically uns... more Limited information exists about the epidemiology, management and outcomes of hemodynamically unstable patients with acute pulmonary embolism (PE). We aimed to evaluate the prevalence and outcomes of unstable PE, and to assess the acute management in routine clinical practice. This study included 34,380 patients from the RIETE registry with PE between 2001 and 2016. Primary outcomes included all-cause and PE-specific 30-day mortality. We used multivariable adjustments to calculate hazard ratios among unstable patients who did and did not receive reperfusion. Overall, 1207 patients (3.5%) presented with hemodynamic instability. All-cause 30-day mortality was 14% and 5.4% in those with versus those without hemodynamic instability (P < 0.001). Two hundred and thirty eight (20%) unstable patients received reperfusion therapy. After multivariable adjustment, reperfusion therapy was associated with non-significantly reduced 30-day all-cause mortality (hazard ratio [HR] 0.71; 95% CI, 0....

Research paper thumbnail of Clinical Course of Venous Thromboembolism in Patients with Pancreatic Cancer: Insights from the RIETE Registry

Thrombosis and haemostasis, 2018

Research paper thumbnail of Lipoprotein (a) levels and outcomes in stable outpatients with symptomatic artery disease

Atherosclerosis, Jan 4, 2018

Although genetic and epidemiological studies support that people with high lipoprotein (a) [Lp(a)... more Although genetic and epidemiological studies support that people with high lipoprotein (a) [Lp(a)] levels are at an increased risk for arterial disease, its prognostic value in patients with established artery disease has not been consistently evaluated. FRENA is a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We assessed the risk for subsequent myocardial infarction, ischemic stroke or limb amputation according to Lp(a) levels at baseline. As of December 2016, 1503 stable outpatients were recruited. Of these, 814 (54%) had levels <30 mg/dL, 319 (21%) had 30-50 mg/dL and 370 (25%) had ≥50 mg/dL. Over a mean follow-up of 36 months, 294 patients developed subsequent events (myocardial infarction 122, ischemic stroke 114, limb amputation 58) and 85 died. On multivariable analysis, patients with Lp(a) levels of 30-50 mg/dL were at a higher risk for myocardial infarction (hazard ratio [HR]: 4.67; 95%CI: 2.77-7.85), ischemi...

Research paper thumbnail of Long-term outcomes of isolated superficial vein thrombosis in patients with active cancer

Thrombosis research, Jan 20, 2018

Cancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at high... more Cancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at higher risk of death than similar cancer patients who do not develop DVT or PE. The impact of isolated superficial venous thrombosis (SVT) (i.e. without DVT or PE) on the prognosis of cancer patients is unknown. Data from the OPTIMEV, multicentre, observational study, to compare at 3 years the incidences of death, DVT-PE recurrence and bleeding of cancer patients with objectively confirmed SVT vs. cancer patients with DVT (matched 1:2 on age, sex, cancer stage) and vs. patients with SVT without cancer (matched 1:3 on age and sex). Cancer patients with SVT (n = 34) had a high risk of death (23.2%patient-year(PY)), that was similar to that of cancer patients with DVT (aHR = 1.0[0.6-1.9]) and higher to that of SVT patients without cancer (aHR = 9.0[3.5-23.1]). Cancer patients with SVT received anticoagulants for a median duration of 45 days and had a high risk of DVT-PE recurrence (6.0%PY), sim...

Research paper thumbnail of Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism

The American journal of medicine, Jan 25, 2018

Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patie... more Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism has been also established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined. The current study analyzed clinical characteristics, time-course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5,717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism). During anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 ...

Research paper thumbnail of Performance of Early Prognostic Assessment Independently Predicts the Outcomes in Patients with Acute Pulmonary Embolism

Thrombosis and haemostasis, 2018

Research paper thumbnail of Validation of a prognostic score for hidden cancer in unprovoked venous thromboembolism

PloS one, 2018

The usefulness of a diagnostic workup for occult cancer in patients with venous thromboembolism (... more The usefulness of a diagnostic workup for occult cancer in patients with venous thromboembolism (VTE) is controversial. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to perform a nested case-control study to validate a prognostic score that identifies patients with unprovoked VTE at increased risk for cancer. We dichotomized patients as having low- (≤2 points) or high (≥3 points) risk for cancer, and tried to validate the score at 12 and 24 months. From January 2014 to October 2016, 11,695 VTE patients were recruited. Of these, 1,360 with unprovoked VTE (11.6%) were eligible for the study. At 12 months, 52 patients (3.8%; 95%CI: 2.9-5%) were diagnosed with cancer. Among 905 patients (67%) scoring ≤2 points, 22 (2.4%) had cancer. Among 455 scoring ≥3 points, 30 (6.6%) had cancer (hazard ratio 2.8; 95%CI 1.6-5; p<0.01). C-statistic was 0.63 (95%CI 0.55-0.71). At 24 months, 58 patients (4.3%; 95%CI: 3.3-5.5%) were diagnosed with cancer. Among 905 pat...

Research paper thumbnail of Systematic review of efficacy and safety of retrievable inferior vena caval filters

Thrombosis research, May 1, 2018

Inferior vena caval (IVC) filters are used with the premise of preventing pulmonary embolism (PE)... more Inferior vena caval (IVC) filters are used with the premise of preventing pulmonary embolism (PE). Concerns for complications due to longstanding dwell time led to development of retrievable filters, which were cleared by the Food and Drug Administration (FDA) in early 2000’s. This temporally correlated with permissive recommendations for use in several clinical scenarios1 and frequent utilization of IVC filters. Among Medicare Fee-For-Service beneficiaries with PE, one in every 6 received an IVC filter.2 Yet, overall evidence for efficacy of IVC filters remains limited.3,4 Further, some retrievable filters possess distinct features that may impact their efficacy and safety. At one hand, such features are presumably advantageous making them amenable to removal (e.g. when a patient no longer has contraindication to anticoagulation). However, alternative anchoring mechanisms may make these filters susceptible to tilting (with potential to reduce retrievability, but also to reduce efficacy), migration, perforation, and injury to adjacent organs. 5,6 We performed a systematic review of the prospective controlled studies to determine the efficacy and safety of retrievable IVC filters.

Research paper thumbnail of Management appropriateness and outcomes of patients with acute pulmonary embolism

The European respiratory journal, 2018

The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary ... more The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary embolism (PE) has not been well defined by previous studies.In this prospective cohort study of patients admitted to a respiratory department (n=2096), we evaluated whether patients with PE had better outcomes if they were acutely managed according to international guidelines. Outcomes consisted of all-cause mortality, PE-related mortality, recurrent venous thromboembolism (VTE) and major bleeding events during the first month of follow-up after diagnosis.Overall, 408 patients (19% (95% CI 18-21%)) did not receive guideline-adherent PE management. Patients receiving non-adherent management were significantly more likely to experience all-cause mortality (adjusted odds ratio (OR) 2.39 (95% CI 1.57-3.61) or PE-related mortality (adjusted OR 5.02 (95% CI 2.42-10.42); p<0.001) during follow-up. Non-adherent management was also a significant independent predictor of recurrent VTE (OR 2.19 ...

Research paper thumbnail of Impact of Thrombus Sidedness on Presentation and Outcomes of Patients with Proximal Lower Extremity Deep Vein Thrombosis

Seminars in thrombosis and hemostasis, Jan 12, 2018

Small studies have suggested differences in demographics and outcomes between left- and right-sid... more Small studies have suggested differences in demographics and outcomes between left- and right-sided deep vein thrombosis (DVT), and also unilateral versus bilateral DVT. We investigated the clinical presentation and outcomes of patients with DVT based on thrombus sidedness. The authors used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) database (2001-2016) to identify patients with symptomatic proximal lower-extremity DVT. Main outcomes included cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality. Overall, 30,445 patients were included. The majority of DVTs occurred in the left leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; < 0.001 for chi-squared test comparing all three groups). Comorbidities were relatively similar in those with left-sided and right-sided DVT. Compared with those with left-sided DVT, patients with right-sided DVT had higher relative frequency of PE (26% versus 23%, < 0.001) and 1-year mor...

Research paper thumbnail of Predictors of Post-Thrombotic Ulcer after Acute DVT: The RIETE Registry

Thrombosis and haemostasis, 2018

In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is the most debilita... more In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is the most debilitating and end-stage clinical expression of the post-thrombotic syndrome (PTS). To date, risk factors for PTS-related ulcer in DVT patients have not been identified.We used the international observational RIETE registry to assess the evolution of PTS signs and symptoms during a 3-year follow-up period and to identify independent predictors of PTS ulcer at 1 year in patients with acute DVT.Among 1,866 eligible patients, cumulative rates of PTS ulcer at 1, 2 and 3 years were 2.7% ( = 50), 4.3% ( = 54) and 7.1% ( = 60), respectively. The proportion of patients with PTS symptoms at 1, 2 or 3 years remained stable (≈40%), while the proportion of patients with PTS signs increased slightly over time (from 49 to 53%). Prior history of venous thromboembolism (VTE) (odds ratio [OR] = 5.5 [2.8-10.9]), diabetes (OR = 2.3 [1.1-4.7]), pre-existing leg varicosities (OR = 3.2 [1.7-6.1]) and male sex (OR =...

Research paper thumbnail of Anticoagulant therapy for venous thromboembolism in patients with inflammatory bowel disease

European journal of gastroenterology & hepatology, Jan 16, 2018

There is lack of evidence to guide the type, intensity, and the duration of anticoagulation follo... more There is lack of evidence to guide the type, intensity, and the duration of anticoagulation following venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD). Registro Informatizado Enfermedad Trombo Embólica (RIETE) is an ongoing, multicenter, observational registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We used the RIETE database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in noncancer patients with or without IBD. As of October 2014, 41 927 patients without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation was similar in patients with VTE during an acute flare (8.3±8.8 months), in remission (9.4±11.5 months), or without IBD (10.0±12.8 months). The rate of VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI: 3.23-19.2; and 5.85, 95% CI: 5.46-6.2...