C. Falgá

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.

Low-molecular-weight or Unfractionated Heparin in Venous Thromboembolism: The Influence of Renal Function

BACKGROUND In patients with acute venous thromboembolism and renal insufficiency, initial therapy with unfractionated heparin may have some advantages over low-molecular-weight heparin. METHODS We used the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Registry data to evaluate the 15-day outcome in 38,531 recruited patients. We used propensity score matching to compare patients treated with unfractionated heparin with those treated with low-molecular-weight heparin in 3 groups stratified by creatinine clearance levels at baseline: >60 mL/min, 30 to 60 mL/min, or <30 mL/min. RESULTS Patients initially receiving unfractionated heparin therapy (n = 2167) more likely had underlying diseases than those receiving low-molecular-weight heparin (n = 34,665). Propensity score-matched groups of patients with creatinine clearance levels >60 mL/min (n = 1598 matched pairs), 30 to 60 mL/min (n = 277 matched pairs), and <30 mL/min (n = 210 matched pairs) showed an increased 15-day mortality for unfractionated heparin compared with low-molecular-weight heparin (4.5% vs 2.4% [P = .001], 5.4% vs 5.8% [P = not significant], and 15% vs 8.1% [P = .02], respectively), an increased rate of fatal pulmonary embolism (2.8% vs 1.2% [P = .001], 3.2% vs 2.5% [P = not significant], and 5.7% vs 2.4% [P = .02], respectively), and a similar rate of fatal bleeding (0.3% vs 0.3%, 0.7% vs 0.7%, and 0.5% vs 0.0%, respectively). Multivariate analysis confirmed that patients treated with unfractionated heparin were at increased risk for all-cause death (odds ratio, 1.8; 95% confidence interval, 1.3-2.4) and fatal pulmonary embolism (odds ratio, 2.3; 95% confidence interval, 1.5-3.6). CONCLUSIONS In comparison with low-molecular-weight heparin, initial therapy with unfractionated heparin was associated with a higher mortality and higher rate of fatal pulmonary embolism in patients with creatinine clearance levels >60 mL/min or <30 mL/min, but not in those with levels between 30 and 60 mL/min.

Venous thromboembolism in nonagenarians Findings from the RIETE Registry

The balance between the efficacy and safety of anticoagulant therapy in patients aged >/=90 years with venous thromboembolism (VTE) is uncertain. RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We evaluated the efficacy and safety of anticoagulant therapy during the first three months in all patients aged >/=90 years. In addition, we tried to identify those at a higher risk for VTE. Of 21,873 patients enrolled from March 2001 to February 2008, 610 (2.8%) were aged >/=90 years. Of these, 307 (50%) presented with pulmonary embolism (PE), 240 (39%) had immobility >/=4 days, and 271 (44%) had abnormal creatinine levels. During the first three months of therapy, 140 patients aged >/=90 years (23%) died. Of these, 45 (32%) died of PE (34 of the initial episode, 11 of recurrent PE), 18 (13%) had fatal bleeding. Recent immobility >/=4 days was the most common risk factor for VTE (240 of 610 patients, 39%), but only 54 of them (22%) had received thromboprophylaxis. The most frequent causes for immobility were senile dementia, acute infection, trauma or decompensated heart failure. The duration of immobility was <4 weeks in 126 patients (52%), and most of them were bedridden at home. In conclusion, one in every four VTE patients aged >/=90 years died during the first three months of therapy. Of these, one in every three died of PE, one in every eight had fatal bleeding. Identifying at-risk patients may help to prevent some of these deaths.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs

BACKGROUND Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.

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 Tromboembólica (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.

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

Abstract 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; p < 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%, p < 0.001) and 1‐year mortality (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.00‐1.18). This difference in mortality did not persist after multivariable adjustment (OR: 1.01; 95% CI: 0.93‐1.1). Patients with bilateral DVT had a greater burden of comorbidities such as heart failure, and recent surgery compared with those with unilateral DVT (p < 0.001), and higher relative frequency of PE (48%), and 1‐year mortality (24.1%). Worse outcomes in patients with bilateral DVT were attenuated but persisted after multivariable adjustment for demographics and risk factors (OR: 1.64; 95% CI: 1.43‐1.87). Patients with bilateral DVT had worse outcomes during and after discontinuation of anticoagulation. There is a left‐sided preponderance for proximal lower‐extremity DVT. Compared with those with left‐sided DVT, patients with right‐sided DVT have slightly higher rates of PE. Bilateral DVT is associated with markedly worse short‐term and 1‐year outcomes.

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

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 patients scoring ≤2 points, 26 (2.9%) had cancer. Among 455 patients scoring ≥3 points, 32 (7%) had cancer (hazard ratio 2.6; 95%CI 1.5–4.3; p<0.01). C-statistic was 0.61 (95%CI, 0.54–0.69). We validated our prognostic score at 12 and 24 months, although prospective cohort validation is needed. This may help to identify patients for whom more extensive screening workup may be required.