Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients. METHODS: COPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)). RESULTS: Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7). CONCLUSIONS: COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients

Platelet count and outcome in patients with acute venous thromboembolism

The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (450,000/\ub5l) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85-3.95; 1.43 [1.18-1.72]; 1.23 [1.03-1.47]; and 2.13 [1.65-2.75]) and fatal bleeding (OR: 3.70 [1.92-7.16], 2.10 [1.48-2.97], 1.29 [0.88-1.90] and 2.49 [1.49-4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE

A clinical prognostic model for the identification of low-risk patients with acute symptomatic pulmonary embolism and active cancer.

BACKGROUND: Physicians need a specific risk-stratification tool to facilitate safe and cost-effective approaches to the management of patients with cancer and acute pulmonary embolism (PE). The objective of this study was to develop a simple risk score for predicting 30-day mortality in patients with PE and cancer by using measures readily obtained at the time of PE diagnosis. METHODS: Investigators randomly allocated 1,556 consecutive patients with cancer and acute PE from the international multicenter Registro Informatizado de la Enfermedad TromboEmb\uf3lica to derivation (67%) and internal validation (33%) samples. The external validation cohort for this study consisted of 261 patients with cancer and acute PE. Investigators compared 30-day all-cause mortality and nonfatal adverse medical outcomes across the derivation and two validation samples. RESULTS: In the derivation sample, multivariable analyses produced the risk score, which contained six variables: age > 80 years, heart rate 65 110/min, systolic BP < 100 mm Hg, body weight < 60 kg, recent immobility, and presence of metastases. In the internal validation cohort (n = 508), the 22.2% of patients (113 of 508) classified as low risk by the prognostic model had a 30-day mortality of 4.4% (95% CI, 0.6%-8.2%) compared with 29.9% (95% CI, 25.4%-34.4%) in the high-risk group. In the external validation cohort, the 18% of patients (47 of 261) classified as low risk by the prognostic model had a 30-day mortality of 0%, compared with 19.6% (95% CI, 14.3%-25.0%) in the high-risk group. CONCLUSIONS: The developed clinical prediction rule accurately identifies low-risk patients with cancer and acute PE

Outcomes in Neurosurgical Patients Who Develop Venous Thromboembolism: A Review of the RIETE Registry

OBJECTIVES: Registro Informatizado de Enfermedad TromboEmb\uf3lica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of bleeding or VTE and the influence of anticoagulation on these outcomes. METHODS: Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery. RESULTS: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism [PE], no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058). CONCLUSIONS: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation

Factors Associated with elevated Pulmonary Arterial Pressure Levels on the Echocardiographic Assessment in Patients with Prior Pulmonary Embolism

BACKGROUND: Factors associated with the detection of raised systolic pulmonary artery pressure (sPAP) levels in patients with a prior episode of pulmonary embolism (PE) are not well known. METHODS: We used the RIETE Registry database to identify factors associated with the finding of sPAP levels 6550 mm Hg on trans-thoracic echocardiography, in 557 patients with a prior episode of acute, symptomatic PE. RESULTS: Sixty-two patients (11.1%; 95% CI: 8.72-14.1) had sPAP levels 6550 mm Hg. These patients were more likely women, older, and more likely had chronic lung disease, heart failure, renal insufficiency or leg varicosities than those with PAP levels <50mm Hg. During the index PE event, they more likely had recent immobility, and more likely presented with hypoxemia, increased sPAP levels, atrial fibrillation, or right bundle branch block. On multivariate analysis, women aged 6570 years (hazard ratio [HR]: 2.0; 95% CI: 1.0-3.7), chronic heart or chronic lung disease (HR: 2.4; 95% CI: 1.3-4.4), atrial fibrillation at PE presentation (HR: 2.8; 95% CI: 1.3-6.1) or varicose veins (HR: 1.8; 95% CI: 1.0-3.3) were all associated with an increased risk to have raised sPAP levels. Chronic heart disease, varicose veins, and atrial fibrillation were independent predictors in women, while chronic heart disease, atrial fibrillation, a right bundle branch block or an S1Q3T3 pattern on the electrocardiogram were independent predictors in men. CONCLUSIONS: Women aged 6570 years more likely had raised sPAP levels than men after a PE episode. Additional variables influencing this risk seem to differ according to gender

D-dimer levels and 90-day outcome in patients with acute pulmonary embolism with or without cancer

BACKGROUND: The prognostic value of D-dimer testing in patients with acute pulmonary embolism (PE) has not been thoroughly studied. METHODS: We used the RIETE Registry data to assess the 90-day prognostic value of increased IL Test D-dimer levels at baseline in patients with PE, according to the presence or absence of cancer. RESULTS: As of May 2013, 3,283 patients with acute PE underwent D-dimer testing using IL Test D-dimer. Among 2,588 patients without cancer, those with D-dimer levels in the highest quartile had a higher rate of fatal PE (2.6% vs. 0.9%; p=0.002), fatal bleeding (1.1% vs. 0.3%; p=0.017) and all-cause death (9.1% vs. 4.4%; p<0.001) at 90 days compared with those with levels in the lowest quartiles. Among 695 patients with cancer, those with levels in the highest quartile had a similar rate of fatal PE or fatal bleeding but higher mortality (35% vs. 24%; p<0.01). On multivariate analysis, non-cancer patients with D-dimer levels in the highest quartile had an increased risk for fatal PE (odds ratio [OR]: 3.3; 95% CI: 1.6-6.6), fatal bleeding (OR: 4.3; 95% CI: 1.4-13.7) and all-cause death (OR: 2.1; 95% CI: 1.4-3.1) compared with patients with levels in the lowest quartiles. CONCLUSIONS: Non-cancer patients with acute PE and IL Test D-dimer levels in the highest quartile had an independently higher risk for fatal PE, fatal bleeding and all-cause death at 90 days than those with levels in the lowest quartiles. In patients with cancer, D-dimer levels failed to predict fatal PE or fatal bleeding

Influence of recent immobilization and recent surgery on mortality in patients with pulmonary embolism

BACKGROUND: The influence of recent immobilization or surgery on mortality in patients with pulmonary embolism (PE) is not well known. METHODS: We used the Registro Informatizado de Enfermedad TromboEmb\uf3lica (RIETE) data to compare the 3-month mortality rate in patients with PE, with patients categorized according to the presence of recent immobilization, recent surgery, or neither. RESULTS: Of 18,028 patients with PE, 4169 (23%) had recent immobilization, 2212 (12%) had recent surgery, and 11,647 (65%) had neither. The all-cause mortality was 10.0% (95% confidence interval [CI] 9.5-10.4), and the PE-related mortality was 2.6% (95% CI 2.4-2.9). One in every two patients who died from PE had recent immobilization (43%) or recent surgery (6.7%). Only 25% of patients with immobilization had received prophylaxis, as compared with 65% of the surgical patients. Fatal PE was more common in patients with recent immobilization (4.9%; 95% CI 4.3-5.6) than in those with surgery (1.4%; 95% CI 1.0-2.0) or those with neither (2.1%; 95% CI 1.8-2.3). On multivariate analysis, patients with immobilization were at increased risk for fatal PE (odds ratio 2.2; 95% CI 1.8-2.7), with no differences being seen between patients immobilized in hospital or in the community. CONCLUSIONS: Forty-three per cent of patients dying from PE had recent immobilization for 654 days. Many of these deaths could have been prevented

Fondaparinux in the initial and long-term treatment of venous thromboembolism

BACKGROUND: Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice. METHODS: We used the Registro Informatizado de Enfermedad Tromboemb\uf3lica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer. RESULTS: Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05). CONCLUSIONS: An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients

Outcomes during anticoagulation in patients with symptomatic vs. incidental splanchnic vein thrombosis

Introduction: Current guidelines recommend the use of anticoagulant therapy in patients with symptomatic splanchnic vein thrombosis (SVT) and suggest no routine anticoagulation in those with incidental SVT. Methods: We used the RIETE (Registro Informatizado Enfermedad Trombo Emb\uf3lica) registry to assess the rate and severity of symptomatic venous thromboembolism (VTE) recurrences and major bleeding events appearing during the course of anticoagulation in patients with symptomatic or incidental SVT. Results: In March 2017, 521 patients with SVT were recruited. Of them, 212 (41%) presented with symptomatic SVT and 309 had incidental SVT. Most (93%) patients received anticoagulant therapy (median, 147 days). During the course of anticoagulation, 20 patients developed symptomatic VTE recurrences (none died) and 26 had major bleeding (fatal bleeding, 5). On multivariable analysis, patients with incidental SVT had a non-significantly higher risk for symptomatic VTE recurrences (adjusted hazard ratio [HR]: 2.04; 95%CI: 0.71\u20135.88) and a similar risk for major bleeding (HR: 1.12; 95%CI: 0.47\u20132.63) than those with symptomatic SVT. Active cancer was associated with at increased risk for VTE recurrences (HR: 3.06; 95%CI: 1.14\u20138.17) and anaemia (HR: 4.11; 95%CI: 1.45\u201311.6) or abnormal prothrombin time (HR: 4.10; 95%CI: 1.68\u201310.1) were associated with at increased risk for major bleeding. Conclusions: The rates of recurrent SVT and major bleeding were similar between patients with incidental or symptomatic SVT. Because the severity of bleeding complications during anticoagulation may outweigh the severity of VTE recurrences in both groups, further studies should identify those SVT patients who benefit from anticoagulant therapy

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used