Patient-Level, Institutional, and Temporal Variations in Use of Imaging Modalities to Confirm Pulmonary Embolism.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%, P<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, P<0.001). CONCLUSIONS: 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.

Automatic or manual arterial path for the ankle-brachial differences pulse wave velocity.

An automated method for measuring arterial path length with devices that determine pulse wave velocity (PWV) in peripheral arteries is frequently applied. We aimed to compare arterial path length measurements based on mathematical height-based formulas with those measured manually and to assess whether the ankle-brachial difference (abD-PWV) measured with the VOPITB device is comparable to that obtained by manual measurements. In 245 patients, a metric measuring tape was used to determine the arterial path length from the suprasternal notch to the midpoint of the VOPITB cuffs wrapped around the extremities, and the results were compared with those obtained with height-based formulas. We examined the relationship between the abD-PWV measured with both methods. The arterial path length measured manually was shorter than that calculated automatically by 5 ± 2 and 30 ± 4 cm-of 13% and 21% for the arms and legs, respectively (difference of 13% and 21%). As a result, the abD-PWV calculated with the automatic method was greater (automatic abD-PWV vs. manual: 462 ± 90 vs. 346 ± 79 cm/s). The Blant Altman plot showed a percentage error of: 15,2%, 7,5% and 17,3% for heart-brachial, heart-ankle length and abD-PWV respectively. In conclusion there were significant differences between manual and automated arterial length measurements and it translates into difference abD-PWV calculate from both methods. However, the Bland-Alman plot showed that abD-PWV was comparable for both techniques. The advantages of height-based formulas for the calculation of arterial path lengths suggest that they may be the recommended method for measuring the abD-PWV.

Multivariate analysis for coronary heart disease in heterozygote familial hypercholesterolemia patients.

AIM: rs599839 polymorphism has been related with low levels of cholesterol and reduced coronary heart disease (CHD). METHODS: We investigated the frequency of this polymorphism in patients with heterozygous familial hypercholesterolemia (HeFH) in the Spanish familial hypercholesterolemia cohort, 230 with and 202 without CHD. Results & discussion: A lower G-allele prevalence was observed in HeFH patients with CHD with respect to controls, 35 versus 45%, respectively (p = 0.029), suggesting a protective effect. However, it was found that there was no association between rs599839 alleles and CHD in the multivariate analysis. CONCLUSION: The frequency of the protective G-allele of the rs599839 polymorphism was lower in HeFH patients with CHD compared with those HeFH patients without CHD. However, its role in HeFH may be masked by very high levels of cholesterol.

Clinical Characteristics and Outcomes of Patients with Lung Cancer and Venous Thromboembolism.

Background The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer <3 months before, 1,270 (74%) had metastases, and 1,250 (72%) had no additional risk factors for VTE. During anticoagulation (median, 93 days), 166 patients had symptomatic VTE recurrences (recurrent DVT: 86, PE: 80), 63 had major bleeding (intracranial 11), and 870 died. The recurrence rate was twofold higher than the major bleeding rate during the first month, and over threefold higher beyond the first month. Fifty-seven patients died of PE and 15 died of bleeding. Most fatal PEs (84%) and most fatal bleeds (67%) occurred within the first month of therapy. Nine patients with fatal PE (16%) died within the first 24 hours. Of 72 patients dying of PE or bleeding, 15 (21%) had no metastases and 29 (40%) had the VTE shortly after surgery or immobility. Conclusion Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.

Raised Fibrinogen Levels and Outcome in Outpatients With Peripheral Artery Disease.

The influence of raised fibrinogen levels on outcome in stable outpatients with peripheral arterial disease (PAD) has not been consistently investigated. We used data from the Factores de Riesgo y ENfermedad Arterial (FRENA) registry to compare ischemic events, major bleeding, and mortality in stable outpatients with PAD, according to their baseline plasma fibrinogen levels. Of 1363 outpatients with PAD recruited in FRENA, 558 (41%) had fibrinogen levels >450 mg/100 mL. Over 18 months, 43 patients presented with acute myocardial infarction, 37 had an ischemic stroke, 51 underwent limb amputation, 19 had major bleeding, and 90 died. Compared to patients with normal levels, those with raised fibrinogen levels had an over 2-fold higher rate of ischemic stroke (rate ratio [RR]: 2.30; 95% confidence interval [CI]: 1.19-4.59), limb amputation (RR: 2.58; 95% CI: 1.46-4.67), or death (RR: 2.27; 95% CI: 1.49-3.51) and an over 3-fold higher rate of major bleeding (RR: 3.90; 95% CI: 1.45-12.1). On multivariate analysis, patients with raised fibrinogen levels had an increased risk of developing subsequent ischemic events (hazard ratio [HR]: 1.61; 95% CI: 1.11-2.32) and major bleeding (HR: 3.42; 95% CI: 1.22-9.61). Stable outpatients with PAD and raised plasma fibrinogen levels had increased rates of subsequent ischemic events and major bleeding.

Predicting Cardiovascular Events in Familial Hypercholesterolemia: The SAFEHEART Registry (Spanish Familial Hypercholesterolemia Cohort Study).

BACKGROUND: Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. METHODS: SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. RESULTS: We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant (P=0.023 and P=0.045). CONCLUSIONS: The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02693548.

Cilostazol and outcome in outpatients with peripheral artery disease.

BACKGROUND: Cilostazol increases the walking distance in patients with intermittent claudication, but there is scarce evidence of any effect on the risk for subsequent ischemic events, bleeding or death. PATIENTS AND METHODS: We used data from the FRENA Registry to compare the clinical outcome in stable outpatients with intermittent claudication, according to the use of cilostazol. RESULTS: As of January 2013, 1,317 patients with intermittent claudication were recruited in FRENA, of whom 191 (14.5%) received cilostazol. Over a mean follow-up of 18months, 39 patients developed myocardial infarction, 23 ischemic stroke, 20 underwent limb amputation, 15 had major bleeding and 70 died. There were no significant differences in the rate of subsequent ischemic events, major bleeding or death between patients receiving or not receiving cilostazol. On multivariate analysis, the use of cilostazol had no influence on the risk for subsequent myocardial infarction (hazard ratio [HR]: 0.97; 95% CI: 0.33-20.8), ischemic stroke (HR: 1.46; 95% CI: 0.48-4.43), limb amputation (HR: 0.34; 95% CI: 0.04-20.6), major bleeding (HR: 1.52; 95% CI: 0.33-7.09) or death (HR: 0.90; 95% CI: 0.40-20.0). CONCLUSIONS: In stable outpatients with intermittent claudication, the use of cilostazol was not associated with increased rates of subsequent ischemic events, major bleeding or death.

Influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism.

BACKGROUND: The influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism (VTE) has not been thoroughly studied. METHODS: We used the RIETE Registry data to compare the 3-month mortality rate in cancer patients with VTE, with patients categorized according to the presence of recent immobilization, surgery or neither. The major outcomes were fatal pulmonary embolism (PE) and fatal bleeding within the first 3 months. RESULTS: Of 6,746 patients with active cancer and acute VTE, 1,224 (18%) had recent immobilization, 1,055 (16%) recent surgery, and 4,467 (66%) had neither. The all-cause mortality was 23.4% (95% CI: 22.4-24.5), and the PE-related mortality: 2.5% (95% CI: 2.1-2.9). Four in every ten patients dying of PE had recent immobilization (37%) or surgery (5.4%). Only 28% of patients with immobilization had received prophylaxis, as compared with 67% of the surgical. Fatal PE was more common in patients with recent immobilization (5.0%; 95% CI: 3.9-6.3) than in those with surgery (0.8%; 95% CI: 0.4-1.6) or neither (2.2%; 95% CI: 1.8-2.6). On multivariate analysis, patients with immobilization were at an increased risk for fatal PE (odds ratio: 1.8; 95% CI: 1.2-2.5). CONCLUSIONS: One in every three cancer patients dying of PE had recent immobilization for ≥ 4 days. Many of these deaths could have been prevented with adequate thromboprophylaxis.

Clinical outcome of stable outpatients with coronary, cerebrovascular or peripheral artery disease, and atrial fibrillation.

BACKGROUND: The influence of atrial fibrillation (AF) on outcome in patients with symptomatic atherosclerotic disease has not been thoroughly studied. METHODS: FRENA is an ongoing registry of stable outpatients with coronary (CAD), cerebrovascular (CVD), or peripheral (PAD) artery disease. With the aim to guide therapy, we assessed the incidence of subsequent myocardial infarction (MI), ischemic stroke or major bleeding in patients with AF, according to initial presentation. RESULTS: As of June 2011, 3848 patients were recruited: 1436 had CAD, 1104 CVD, and 1308 had PAD. Of these, 470 (12%) had AF: 151 patients with CAD, 157 with CVD, and 162 with PAD. Over a mean follow-up of 16 ± 13 months, 19 patients with AF developed acute MI, 22 ischemic stroke and 7 bled. Among AF patients with CAD, the incidence of subsequent MI (5.00 events per 100 patient-years; 95% CI: 2.54-8.91) was non-significantly higher than that of stroke (1.48; 95% CI: 0.38-4.04) or major bleeding (1.47; 95% CI: 0.37-4.01). Among those with CVD, the incidence of stroke (5.61; 95% CI: 2.95-9.75) exceeded that of MI (no events) or major bleeding (0.51; 95% CI: 1.24-6.36). Among those with PAD, the incidence of MI (4.41; 95% CI: 2.15-8.10) and stroke (3.93; 95% CI: 1.82-7.46) were similar. CONCLUSIONS: CAD patients with AF are at a higher risk of subsequent MI than of stroke. Among those with CVD, the risk of stroke far exceeds that of MI. Those with PAD have a high and similar risk for both events.

Telmisartan improves insulin resistance in patients with low cytokine levels.

UNLABELLED: Metabolic syndrome (MS) is a disease with an inflammatory component. Telmisartan improves insulin resistance in MS, but its relationship with the inflammatory state is unknown. We investigated the effect of 3-month telmisartan therapy on homeostatic model assessment-insulin resistance (HOMA-IR) in hypertensive subjects with MS with regard to the levels of circulating plasma cytokines. METHODS: A total of 42 patients were included in this study; 30 were men (71%), aged 50 ± 8.2 years (mean ± SD). Cytokines and metabolic parameters were analyzed before and after treatment with telmisartan. RESULTS: Twenty-eight patients showed low plasma levels of cytokines (group 1) similar to control subjects, and 14 showed high levels (group 2). Treatment with telmisartan diminished by 35% HOMA-IR in group 1 (4.5 ± 3.1 vs 2.9 ± 2.1), without improvement in group 2. In the multivariate analysis, the predictors of improvement of HOMA-IR in response to telmisartan treatment were low levels of cytokines, whereas systolic and diastolic blood pressure and the elevation of high-sensitivity C-reactive protein had a negative effect. CONCLUSIONS: Our study provides evidence of a more favorable effect of telmisartan on glucose homeostasis in patients with MS and low levels of serum cytokines.

[Atorvastatin and oxidized low density lipoprotein antibody. Relationship to age]. / Atorvastatina, anticuerpos LDL oxidada y su relación con la edad.

BACKGROUND AND OBJECTIVES: In hypercholesterolemic patients, we studied the relationships of plasma levels of LDLoxab with cardiovascular variables and its changes after treatment with atorvastatin. PATIENTS AND METHODS: We studied, in 48 patients, the levels of LDLoxab, as well as lipid, oxidative stress and inflammatory biomarkers, at baseline and 24 weeks after treatment with 20mg of atorvastatin. RESULTS: Baseline: a correlation was observed between LDLoxab and age (r= 0.41, P=.03), waist (r=0.38, P=.04) and C reactive protein (r= 0.46, P=.02), but not with other variables. Atorvastatin treatment did not decrease LDLoxab;(mU/mL, median [CI 95%]: baseline: 413 [187-1,196] and 24 weeks: 349 [101-1559]). The percentage change at week 24, was negatively correlated with age (r=-0.37, P=.03) but not with other variables. CONCLUSION: In hypercholesterolemic subjects plasma LDLoxab levels were positively corelated with age, waist and C reactive protein. There were no changes in plasma levels of LDLoxab after treatment with atorvastatin, but the variation was associated with age, suggesting that the immunomodulatory actions may depend of this.

Adverse drug reactions in internal medicine units and associated risk factors.

OBJECTIVES: This study was designed to assess the prevalence of adverse drug reactions (ADRs) in the internal medicine wards of two teaching hospitals, identify the most common ADRs, the principal medications involved, and determine the risk factors implicated in the occurrence of such ADRs. METHODS: All admissions over 10 weeks were followed prospectively using an intensive drug surveillance method to identify ADRs. Clinical laboratory data, the drug prescribed, and ADRs were taken into consideration. Status of nutrition, liver and kidney function at admission, and ADR time were determined. In order to assess drug interactions a software package was used. RESULTS: A total of 405 patients were evaluated, 126 patients (31%) had 128 ADRs, 122 ADRs occurred during hospitalization. Two ADR-related deaths were observed during the study. Reactions affecting the gastrointestinal tract, skin, and hematological system were among the most frequent ADRs. For ADRs observed during admission predictors of its occurrence in a multivariate regression model were: OR (95% CI); more than 12 days' hospitalization: 2.11(1.27-3.47), any drug interaction: 9.33 (5.12-17) and acute change in estimated glomerular filtration rate over admission >20%: 2.46 (1.45-4.2). Worsening of renal function or drug interaction was observed in nine of the ten ADRs. Age, sex, nutrition, and number of drugs used were not related to ADRs. CONCLUSION: A significant prevalence of ADRs was found among hospitalized patients. Duration of hospital admission, changes in renal status during hospitalization and drug interactions seem to be important risk factors for ADRs.

[Glucose metabolism disorders in the risk factor control in Extremadura Study (COFRE Study)]. / Alteraciones del metabolismo glucídico en el estudio de control de factores de riesgo de Extremadura (estudio COFRE).

AIMS: To assess the prevalence and control of glucose metabolism disorders in a population of Extremadura (Spain) with at least one cardiovascular risk factor and to compare the characteristics of these patients with those who were normoglycemic in the risk factor control in Extremadura (COFRE study). PATIENTS AND METHODS: The prevalence and control of cardiovascular risk factors were recorded in a sample of 1,022 patients with at least one cardiovascular risk factor consecutively visiting a primary care office. Of these, 951 patients were included in the analysis. In all patients, fasting glycemia was recorded. Glycated hemoglobin was recorded in diabetic patients. RESULTS: A total of 320 patients (33.6%) were previously known to be diabetic (DM) and 84 (8.8%) had glycemia > or = 126 mg/dl without a previous diagnosis of diabetes (12 with glycemia above 200mg/dl). Impaired fasting glycemia (IFG) was found in 211 (22.2%) and normoglycemia (NG) in 336 (35.3%). Within the DM group, glycemia <126 mg/dl was found in only 31.4% but glycated hemoglobin lower than 7% was found in 46.8%. Triglyceride concentrations were higher in the IFG group than in the NG group (137 + or - 65 mg/dL vs 124 + or - 65 mg/dL, p=0,041). Pulse pressure was also higher, but no differences were found in diastolic blood pressure (DBP) or heart rate. Differences in systolic blood pressure (SBP) were at the limit of significance (DM 139.5 + or - 17 vs NG 136.5 + or - 16 mmHg; p=0.056). No significant differences were found in any of these parameters between the DM and IFG groups. CONCLUSIONS: The prevalence of glucose metabolism disorders was very high in the recruited sample. Patients with IFG showed higher pulse pressure and triglyceride concentrations than those with NG but there were no differences in comparison with DM patients. Diabetic control was poor when assessed by fasting glycemia but glycated hemoglobin showed better control.

[Lipid control in diabetic patients in Extremadura (Spain)]. / Control de la dislipemia en pacientes diabéticos en Extremadura.

OBJECTIVE: Our study aimed to assess the prevalence and degree of control of dyslipemia, using the 2004 National Cholesterol Education Program criteria, as well as the use of cholesterol lowering drugs in a sample of diabetic patients followed up in primary care settings in Extremadura. PATIENTS AND METHODS: In this crosssectional, multicenter study the prevalence and control of cardiovascular risk factors was assessed in a sample of 1022 patients having at least one cardiovascular risk factors who were recruited by general practitioners. A total of 988 subjects were avalaible for statistic analysis of dyslipemia; 320 patients had diabetes mellitus (DM); 178 had at least one cardiovascular disease without diabetes and 506 patients without those diseases were used as control. RESULTS: Total cholesterol and low density lipoprotein (LDL) fraction were higher in the group control. High density lipoprotein (HDL)-cholesterol was lower in the group DM as compared to control. Triglycerides were higher in group DM. Women had higher HDL-cholesterol and lower triglycerides levels than men. Only 26.6% of diabetics subjetcs and 28.9% of group ECV were well controlled; 42.5% of the control group had LDL cholesterol < 130 mg/dl. 13.3% of diabetics patients suffering from coronary artery disease had LDL-cholesterol < 70 mg/dl. They were taking statins: DM, 56.6); ECV 61.6%; and control, 39.4%. From patients who did not take cholesterol lowering drugs 51.6% in group DM and 33.8% in group ECV would need to take them. CONCLUSIONS: The study shows a poor control of dyslipemia in diabetics subjects and high risk patients in spite of lower lipid levels when compared to lower risk population and a more frequent use of cholesterol lowering drugs. Nevertheless, statin use is still lower than currently recommended.

[Influenza vaccination and hospitalization in high risk patients]. / Ingresos hospitalarios y vacunación antigripal en pacientes de alto riesgo.

BACKGROUND AND OBJECTIVE: We aimed to analyze the degree of utilization of influenza vaccines in patients who are 65 years and older with decompensated chronic diseases during the 2006-07 influenza epidemic and to compare it with the 2000-01 epidemic. We also investigated the effectiveness of the influenza vaccination in the prevention of incomes for cardiopulmonary illness in this group. PATIENTS AND METHOD: Six hundred and forty two patients were studied; average (standard deviation) age was 74 (10) years, and 404 (63%) were males. Patients considered as cases had been admitted to hospital due to cardiopulmonary illness during the influenza season. Controls were patients attended at hospital but who had not been hospitalized during that period. RESULTS: The population vaccination rate was 445 (68%). In the vaccination group, 275 (57%) people were 75 year old or more vs 77 (37%) patients in the non-vaccination group (p<0.001); 418 (94%) of the vaccination group had been vaccinated in previous years, vs 96 (46%) in the non-vaccination group (p<0.001). Cases were 337 (68%) vs 305 (31%) controls. Cases had major morbidity, previous hospitalization or pneumonia, as well as 2 or more risk factors -292 (85%) cases vs 225 (73%) controls (p<0.001)-. Factors mostly influencing the possibility of hospitalization were: influenza vaccination (odds ratio [OR]=0.59; 95% confidence interval [CI]: 0.41-0.86; p=0.006), chronic ischemic heart disease (OR=0.59; 95% CI, 0.40-0.88; p=0.009), high blood pressure (OR=1.60; 95% CI, 1.03-2.47), and previous hospitalization (OR=2.40; 95% CI, 1.64-3.49; p<0.001). CONCLUSIONS: In high risk patients, the influenza vaccination rate was improved slightly in the last 6 years. Vaccination was associated with less hospitalization for heart and pulmonary diseases. These benefits of vaccination support future efforts to increase the rates of vaccination among elder patients with chronic diseases, especially if they have not been vaccinated in previous campaigns.

Clinical outcome of patients with venous thromboembolism and renal insufficiency. Findings from the RIETE registry.

There is little information on the clinical outcome of patients with venous thromboembolism and renal insufficiency. RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE). In this analysis we analyzed the three-month outcome in patients with creatinine clearance (CrCl) <30 ml/min. As of March 2007, 1,037 of the 18,251 (5.7%) patients enrolled in RIETE had CrCl <30 ml/min. During the three-month study period these patients had an increased incidence of fatal bleeding, fatal PE, and overall death compared to those with CrCl >30 ml/min. Of the 579 patients presenting with clinically overt PE, 52 (9.0%) died of the initial PE, 13 (2.2%) of recurrent PE, and nine (1.6%) died of bleeding complications. During the first 15 days of therapy the 10% incidence of fatal PE was 10-fold their 1.0% of fatal bleeding. From day 16 to 90, the 1.0% rate of fatal PE was not significantly higher than the 0.5% of fatal bleeding. Of the 458 DVT patients with CrCl <30 ml/min, 14 (3.1%) had fatal bleeding and only one (0.2%) died of PE. In patients with CrCl <30 ml/min presenting with clinically overt PE the main threat is PE itself. On the contrary, in those with DVT the main threat is bleeding.