Statin use and mortality in patients with deep vein thrombosis. Data from the RIETE Registry.

BACKGROUND: The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. METHODS: We used the data in the RIETE registry to examine the association between statin use and mortality at 3 months. We used mixed effects survival models accounting for clinical covariates and clustering of patients in enrolling centers. RESULTS: From January 2009 through April 2022, there were 46,440 patients with isolated DVT in RIETE (in the lower-limbs 42,291, in the upper limbs 4149). Of these, 21 % and 18 %, respectively, were using statins. Statin users were older than non-users (72 ± 12 vs. 62 ± 18 years), and more likely had diabetes, hypertension, prior myocardial infarction or ischemic stroke, or were receiving antiplatelets. The 3-month mortality rates were: 6.0 % vs. 5.8 %, respectively. On multilevel multivariable analysis, the adjusted hazard ratio (aHR) for all-cause death in statin users vs. non-users was 0.77 (95%CI: 0.69-0.86). The 3-month risk of death in statin users was significantly lower than in non-users in patients with upper-limb DVT (aHR: 0.81; 95%CI: 0.72-0.91), distal lower-limb DVT (aHR: 0.48; 95%CI: 0.32-0.72), or proximal lower-limb DVT (aHR: 0.69; 95%CI: 0.50-0.95), and in those receiving simvastatin (aHR: 0.73; 95%CI: 0.60-0.90), atorvastatin (aHR: 0.70; 95%CI: 0.59-0.85), or rosuvastatin (aHR: 0.47; 95%CI: 0.27-0.80). Major bleeding, used as a falsification endpoint, did not show an association with use of statins at 3-month follow-up. CONCLUSIONS: Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users.

Enoxaparin for Long-Term Therapy of Venous Thromboembolism in Patients with Cancer and Renal Insufficiency.

BACKGROUND: The optimal therapy of venous thromboembolism (VTE) in cancer patients with renal insufficiency (RI) is unknown. Current guidelines recommend to use low-molecular-weight heparin over direct oral anticoagulants to treat VTE in cancer patients at high risk of bleeding. METHODS: We used the Registro Informatizado Enfermedad Tromboemb00F3lica (RIETE) registry to compare the 6-month incidence rates of (1) VTE recurrences versus major bleeding and (2) fatal pulmonary embolism (PE) versus fatal bleeding in three subgroups (those with mild, moderate, or severe RI) of cancer patients receiving enoxaparin monotherapy. RESULTS: From January 2009 through June 2022, 2,844 patients with RI received enoxaparin for ≥6 months: 1,432 (50%) had mild RI, 1,168 (41%) moderate RI, and 244 (8.6%) had severe RI. Overall, 68, 62, and 12%, respectively, received the recommended doses. Among patients with mild RI, the rates of VTE recurrences versus major bleeding (4.6 vs. 5.4%) and fatal PE versus fatal bleeding (1.3 vs. 1.2%) were similar. Among patients with moderate RI, VTE recurrences were half as common as major bleeding (3.1 vs. 6.3%), but fatal PE and fatal bleeding were close (1.8 vs. 1.2%). Among patients with severe RI, VTE recurrences were threefold less common than major bleeding (4.1 vs. 13%), but fatal PE was threefold more frequent than fatal bleeding (2.5 vs. 0.8%). During the first 10 days, fatal PE was fivefold more common than fatal bleeding (2.1 vs. 0.4%). CONCLUSION: Among cancer patients with severe RI, fatal PE was fivefold more common than fatal bleeding. The recommended doses of enoxaparin in these patients should be revisited.

Identification of Low-risk Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: Identification of patients with acute symptomatic pulmonary embolism (PE) who are at low-risk for short-term complications to warrant outpatient care lacks clarity. METHOD: In order to identify patients at low-risk for 30-day all-cause and PE-related mortality, we used a cohort of haemodynamically stable patients from the RIETE registry to compare the false-negative rate of four strategies: the simplified Pulmonary Embolism Severity Index (sPESI); a modified (i.e., heart rate cutoff of 100beats/min) sPESI; and a combination of the original and the modified sPESI with computed tomography (CT)-assessed right ventricle (RV)/left ventricle (LV) ratio. RESULTS: Overall, 137 of 3117 patients with acute PE (4.4%) died during the first month. Of these, 41 (1.3%) died from PE, and 96 (3.1%) died from other causes. The proportion of patients categorized as having low-risk was highest with the sPESI and lowest with the combination of a modified sPESI and CT-assessed RV/LV ratio (32.5% versus 16.5%; P<0.001). However, among patients identified as low-risk, the 30-day mortality rate was lowest with the combination of a modified sPESI and CT-assessed RV/LV ratio and highest with the sPESI (0.4% versus 1.0%; P=0.03). The 30-day PE-related mortality rates for patients designated as low-risk by the sPESI, the modified sPESI, and the combination of the original and modified sPESI with CT-assessed RV/LV ratio were 0.7%, 0.4%, 0.7%, and 0.2%, respectively. CONCLUSIONS: The combination of a negative modified sPESI with CT-assessed RV/LV ratio ≤1 identifies patients with acute PE who are at very low-risk for short-term mortality.

Statin use and 30-day mortality in patients with acute symptomatic pulmonary embolism.

BACKGROUND: Statins possess antithrombotic and profibrinolytic properties. The association between statin use and short-term outcomes in patients with acute pulmonary embolism (PE) remains unknown. METHODS: We used the data from the Registro Informatizado de Pacientes con Enfermedad TromboEmbólica registry to compare the 30-day all-cause mortality in patients with acute PE according to the use of statins. Secondary outcome was fatal PE. We used cancer-related mortality as a falsification endpoint. RESULTS: From January 2009 to April 2021, 31 169 patients with PE were recruited. Of these, 5520 (18%) were using statins at baseline: low intensity: 829, moderate: 3636, high intensity: 1055. Statin users were older and had a higher frequency of diabetes, hypertension, or atherosclerotic disease than non-users (P <0.001 for all comparisons). During the first 30 days, 1475 patients died (fatal PE, 255). On multivariable analysis, statin users had a lower risk of all-cause death (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.56-0.76) and fatal PE (OR: 0.42; 95% CI: 0.28-0.62) than non-users. The risk for death was lower in patients using either low- (OR: 0.51; 95% CI: 0.34-0.77), moderate- (OR: 0.68; 95% CI: 0.57-0.81), or high-intensity statins (OR: 0.68; 95% CI: 0.51-0.92). Results did not change in mixed effects logistic regression models with hospitals as a random effect. Statins were not associated with a significant chance in cancer mortality (falsification endpoint). CONCLUSIONS: PE patients using statins at baseline had a significantly lower risk of dying within the first 30 days than non-users. Randomized trials are needed to confirm these data.

Liver status and outcomes in patients without previous known liver disease receiving anticoagulant therapy for venous thromboembolism.

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10-2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04-2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation.

Ventilation/perfusion (V/Q) scanning in contemporary patients with pulmonary embolism: utilization rates and predictors of use in a multinational study.

Ventilation/perfusion (V/Q) imaging and computed tomography pulmonary angiography (CTPA) are common tools for acute pulmonary embolism (PE) diagnosis. Limited contemporary data exist about the utilization of each modality, including the predictors of using V/Q versus CTPA. We used the data from patients diagnosed with PE using V/Q or CTPA from 2007 to 2019 in Registro Informatizado Enfermedad ThromboEmbolica, an international prospective registry of patients with venous thromboembolism. Outcomes was to determine the trends in utilization of V/Q vs. CTPA and, in a contemporary subgroup fitting with current practices, to evaluate predictors of V/Q use with multivariable logistic regression. Among 26,540 patients with PE, 89.2% were diagnosed with CTPA, 7.1% with V/Q and 3.7% with > 1 thoracic imaging modality. Over time, the proportional use of V/Q scanning declined (13.9 to 3.3%, P < 0.001). In multivariable analysis, heart failure history (odds ratio [OR]:1.5; 95% confidence interval [CI] 1.14-1.98), diabetes ([OR 1.71; 95% CI 1.39-2.10]), moderate and severe renal failure (respectively [OR 1.87; 95% CI 1.47-2.38] and [OR 9.36; 95% CI 6.98-12.55]) were the patient-level predictors of V/Q utilization. We also observed an influence of geographical and institutional factors, partly explained by time-limited V/Q availability (less use over weekends) and regional practices. Use of V/Q for the diagnosis of PE decreased over time, but it still has an important role in specific situations with an influence of patient-related, institution-related and logistical factors. Local and regional resources should be evaluated to improve V/Q accessibility than could benefit for this population.

Safety of COVID-19 vaccination in patients with previous cerebral venous sinus thrombosis.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) after coronavirus (COVID-19) vaccination has been reported. There are no data about thrombosis risk in prior CVST patients. The objective of the study was to describe short-term serious adverse events to COVID-19 vaccines in patients with history of CVST. MATERIAL AND METHODS: We present an observational prospective study of patients with known CVST who received COVID-19 vaccination. Serious event rates within 30 days after second dose vaccination (except one dose for Janssen) were evaluated, including recurrences, hospital admission and death. RESULTS: The 62 vaccinated patients received: BNT162b2 (Pfizer-BioNTech) in 43 patients (69.4%), mRNA-1273 (Moderna) in 7 patients (11.3%), AZD1222 (ChAdOx1) in 7 patients (11.3%) and Ad26.COV2.S (Janssen) in 5 patients (8.1%). There were no thrombotic recurrences within 30 days of vaccination (95% confidence interval, 0.0-5.8). There was one death (1.6%), not attributable to the vaccine. CONCLUSIONS: COVID-19 vaccines are safe for previous CVST patients.

Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding.

INTRODUCTION: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. METHODS: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. RESULTS: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68-0.79) for major bleeding, 0.73 (95% CI: 0.67-0.78) for non-major bleeding and 0.82 (95% CI: 0.76-0.87) for bleeding-related death. CONCLUSIONS: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.

Clinical presentation of acute Q fever in Spain: seasonal and geographical differences.

OBJECTIVES: The aims of this study were to improve our understanding of the clinical forms of presentation of acute Q fever in Spain and to determine any possible relationships with geographical and seasonal factors. METHODS: This was a retrospective study of 183 cases of acute Q fever from three Spanish regions, Catalonia, Canary Islands, and La Rioja. RESULTS: The main clinical form of presentation was hepatitis (49.2%), followed by isolate febrile syndrome (31.7%) and pneumonia (19.1%). The proportion of cases presenting as pneumonia was significantly higher in La Rioja (40.7%) than in Catalonia (18.3%) or the Canary Islands (12.9%) (p=0.001). In Catalonia and the Canary Islands, most cases (52.1% and 57.6%, respectively) were diagnosed between March and June, whereas in La Rioja, most cases (51.8%) occurred between November and February. Overall, the proportion of cases presenting as pneumonia was significantly higher in the period from November to February (32.6%) than in the periods March-June (16.0%) and July-October (13.0%) (p=0.01). CONCLUSIONS: Our results suggest the existence of seasonal differences in the presentation of acute Q fever in Spain, with a higher proportion of pneumonic forms in the colder months. Furthermore, we confirmed the existence of geographical differences, with a higher proportion of pneumonic forms in the region of La Rioja, in the north of the country.

A 69-year-old man with excessive sweating of the right hemithorax.

The pure autonomic failure is a rare entity, with only a few cases reported in the literature. The authors describe a case with compensatory excessive sweating of the right hemithorax as an initial manifestation of a pure autonomic failure, and the authors review the clinical characteristics of this disease. A 69-year-old man presented excessive sweating of the right hemithorax. Physical examination revealed orthostatic hypotension. No other neurological features were present. The autonomic study showed a low heart rate response to the Valsalva maneuver and reduced supine plasma norepinephrine levels. A pure autonomic failure was diagnosed. Treatment did not improve patient's symptoms. Anhidrosis with asymmetrical compensatory hyperhidrosis can be the only symptom of a pure autonomic failure. The authors highlight an unusual form of presentation of a rare disease, difficult to diagnose if it is not taken into consideration.