A systematic review of thromboembolic complications and outcomes in hospitalised COVID-19 patients.

Thromboembolic (TE) complications [myocardial infarction (MI), stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE)] are common causes of mortality in hospitalised COVID-19 patients. Therefore, this review was undertaken to explore the incidence of TE complications and mortality associated with TE complications in hospitalised COVID-19 patients from different studies. A literature search was performed using ScienceDirect and PubMed databases using the MeSH term search strategy of "COVID-19", "thromboembolic complication", "venous thromboembolism", "arterial thromboembolism", "deep vein thrombosis", "pulmonary embolism", "myocardial infarction", "stroke", and "mortality". There were 33 studies included in this review. Studies have revealed that COVID-19 patients tend to develop venous thromboembolism (PE:1.0-40.0% and DVT:0.4-84%) compared to arterial thromboembolism (stroke:0.5-15.2% and MI:0.8-8.7%). Lastly, the all-cause mortality of COVID-19 patients ranged from 4.8 to 63%, whereas the incidence of mortality associated with TE complications was between 5% and 48%. A wide range of incidences of TE complications and mortality associated with TE complications can be seen among hospitalized COVID-19 patients. Therefore, every patient should be assessed for the risk of thromboembolic complications and provided with an appropriate thromboprophylaxis management plan tailored to their individual needs.

Non-valvular atrial fibrillation in patients on peritoneal dialysis, prevalence, treatment and professionals involved.

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillars for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1,403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% or in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scores used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.

Prophylactic-dose direct oral anticoagulants for non-hospitalised people with COVID-19: A meta-analysis of randomised controlled trials.

Background: Several reviews have been conducted on thromboprophylaxis in non-hospitalised patients with coronavirus disease 2019 (COVID-19). In this systematic review and meta-analysis, we sought to investigate the impact of prophylactic-dose direct oral anticoagulants (DOACs) in this population. Methods: We searched PubMed, Web of Science, EMBASE and Cochrane Library for randomised controlled trials (RCTs) comparing prophylactic-dose DOACs with placebo or no treatment in non-hospitalised patients with COVID-19 until September 2023. The primary efficacy outcome was a composite of all-cause mortality and thromboembolic events, while major bleeding events were the primary safety outcome. We expressed continuous outcome data as mean differences (MDs) with 95% confidence intervals (CIs) and dichotomous outcome data as risk ratios (RRs) with 95% CIs. Results: We included six RCTs involving 4307 patients. Prophylactic-dose DOAC therapy compared with placebo or no treatment was associated with significantly decreased risks of the composite outcome of all-cause mortality and thromboembolic events (1.43% vs 2.67% (RR = 0.53; 95% CI = 0.34-0.82, P = 0.004, I2 = 3%)). Major bleeding events were infrequent, and we detected no significant differences between patients assigned to prophylactic-dose DOACs vs placebo or no treatment (0.19% vs 0.05% (RR = 2.50; 95% CI = 0.49-12.87, P = 0.27, I2 = 0%)). The use of prophylactic-dose DOACs was also associated with a reduction in venous thromboembolism, with no difference in all-cause mortality, arterial thromboembolism, hospitalisations, and clinically relevant nonmajor bleeding between two groups. Sensitivity analyses with the leave-one-out method for the primary efficacy and safety outcome did not change the effect estimate substantially. Conclusions: We found that prophylaxis-dose DOACs could significantly improve clinical outcomes and reduce venous thrombotic events without increasing the risk of major bleeding events compared with placebo or no treatment in non-hospitalised patients with COVID-19. Registration: PROSPERO: CRD42023466889.

Incidence of thromboembolic events in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

ABSTRACT: The incidence of thromboembolic events (TEs) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) has rarely been reported. The MEDLINE, EMBASE, and the Cochrane Library databases were searched. The primary outcome was the incidence of TEs, and the secondary outcome was the relationship between TEs and overall survival (OS) following ICI therapy. A subgroup analysis of TE incidents was performed according to the TE type and combination regimens. The I2 statistic was used to determine the heterogeneity, and funnel plots and Egger's test were used to assess publication bias. A total of 16,602 patients with NSCLC in 63 experimental arms were included in the analysis. The rate of TEs ranged from 0.1% to 13.8%, and the pooled overall incidence of all-grade TEs was 3% (95% confidence interval [CI], 2%-4%). The pooled rate of high-grade TEs was 1% (95% CI, 1%-2%). The venous and arterial TE rates were 3% (95% CI, 2%-4%) and 1% (95% CI, 1%-2%), respectively. Patients who received immunotherapy + chemoradiotherapy had the highest incidence of TEs (7%). The TE pooled rate was higher in patients treated with combined ICIs than in those treated with mono ICIs (4% vs. 2%). The OS was lower in patients with TEs than in those without TEs (hazard ratio, 1.4; 95% CI, 1.02%-1.92%). The incidence of TEs in NSCLC patients treated with ICIs was reasonable. Nonetheless, clinicians must be aware of potential thrombotic complications and treat them promptly.

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.

Unveiling the Hidden Stroke Threat in Patients With Atrial Fibrillation and Primary Hyperparathyroidism.

Recent American College of Cardiology (ACC), American Heart Association (AHA), American College of Clinical Pharmacy (ACCP), and Heart Rhythm Society (HRS) guidelines suggest that patients with atrial fibrillation (AF) at intermediate to low annual risk of ischemic stroke can benefit from consideration of factors that might modify their risk of stroke. The role of nontraditional risk factors, such as primary hyperparathyroidism (PHPT), remains unexplored. In our study, we investigated the potential association between PHPT and the risk of ischemic stroke in patients with AF. Using data from the Nationwide Inpatient Sample Database, a retrospective cohort study focused on the adult population with AF, we stratified the participants based on PHPT presence. Demographic information, co-morbidities, and hospitalization details were extracted using International Classification of Diseases, Tenth revision codes. Propensity score matching was applied, encompassing over 20 confounding variables, including the risk factors outlined in the CHA2DS2-VASc (Congestive heart failure (C), Hypertension (H), Age ≥75 years (A2), Diabetes Mellitus (D), Stroke/Transient Ischemic Attack (TIA)/Thromboembolism (S2), Vascular disease (V), Age 65-74 years (A), Sex category [female] (Sc)) score. Multivariate logistic regression analysis was performed after matching to assess the independent impact of PHPT as an ischemic stroke risk factor. A total of 2,051 of the identified 395,249 patients with AF had PHPT. The PHPT group had an average age of 74 years and consisted of more women (66.1% vs 53.0%). After matching, it was observed that the PHPT group had longer hospital stays (5 vs 4 days) and higher hospitalization charges ($45,126 vs $36,644). This group exhibited higher rates of ischemic stroke (6.0% vs 4.4%) and mortality (6.3% vs 4.9%). The adjusted outcomes showed a 1.4-fold increased risk for ischemic stroke and a 1.32-fold increased risk for mortality in the PHPT cohort. The subgroup analysis showed a higher incidence of mortality in men with a high CHA2DS2-VASc score. In conclusion, this study highlights a marked association between PHPT and ischemic stroke in patients with AF, independent of the conventional CHA2DS2-VASc score. The potential mechanisms implicated include vascular changes, cardiac dysfunction, and coagulation cascade alterations. The presence of PHPT should be taken into consideration when deciding the assessment of thromboembolic risk.

ABO blood type and thromboembolic complications after intracerebral hemorrhage: An exploratory analysis.

BACKGROUND AND PURPOSE: Non-O blood types are known to be associated with thromboembolic complications (TECs) in population-based studies. TECs are known drivers of morbidity and mortality in intracerebral hemorrhage (ICH) patients, yet the relationships of blood type on TECs in this patient population are unknown. We sought to explore the relationships between ABO blood type and TECs in ICH patients. METHODS: Consecutive adult ICH patients enrolled into a prospective observational cohort study with available ABO blood type data were analyzed. Patients with cancer history, prior thromboembolism, and baseline laboratory evidence of coagulopathy were excluded. The primary exposure variable was blood type (non-O versus O). The primary outcome was composite TEC, defined as pulmonary embolism, deep venous thrombosis, ischemic stroke or myocardial infarction, during the hospital stay. Relationships between blood type, TECs and clinical outcomes were separately assessed using logistic regression models after adjusting for sex, ethnicity and ICH score. RESULTS: Of 301 ICH patients included for analysis, 44% were non-O blood type. Non-O blood type was associated with higher admission GCS and lower ICH score on baseline comparisons. We identified TECs in 11.6% of our overall patient cohort. . Although TECs were identified in 9.9% of non-O blood type patients compared to 13.0% in O blood type patients, we did not identify a significant relationship of non-O blood type with TECs (adjusted OR=0.776, 95%CI: 0.348-1.733, p=0.537). The prevalence of specific TECs were also comparable in unadjusted and adjusted analyses between the two cohorts. In additional analyses, we identified that TECs were associated with poor 90-day mRS (adjusted OR=3.452, 95% CI: 1.001-11.903, p=0.050). We did not identify relationships between ABO blood type and poor 90-day mRS (adjusted OR=0.994, 95% CI:0.465-2.128, p=0.988). CONCLUSIONS: We identified that TECs were associated with worse ICH outcomes. However, we did not identify relationships in ABO blood type and TECs. Further work is required to assess best diagnostic and prophylactic and treatment strategies for TECs to improve ICH outcomes.

Thirty-year outcomes of low-intensity anticoagulation for mechanical aortic valve.

The long-term safety, efficacy, and outcomes of low-intensity anticoagulation for mechanical heart valves remain unclear. This study aimed to evaluate the long-term outcomes of low-intensity anticoagulation therapy after aortic valve replacement (AVR) with a mechanical prosthesis. This retrospective cohort study consulted medical records and conducted a questionnaire to investigate 519 patients who underwent single AVR with the St. Jude Medical bileaflet valve and were in sinus rhythm. All patients were followed up with an international normalized ratio (INR) target of 1.6-2.5, and their INR values were checked throughout the follow-up period. The survival rate, incidence of major adverse cardiac and cerebrovascular events (MACCE), and risk factors for cardiac death and MACCE were investigated. The total follow-up was 9793 patient-years, and the follow-up periods were 19.9 (standard deviation [SD]: 7.9) years. The mean INR was 2.03 (SD: 0.54). Survival rates from cardiac death were 93.6% in 20 years and 85.2% in 30 years. Advanced age ≥ 70 years was the only significant risk factor for cardiac death and MACCE, and the INR < 2.0 was not significant risk factor for MACCE including thromboembolism or bleeding events. Low-intensity anticoagulation with an INR of 1.6-2.5 for patients with sinus rhythm after AVR with a bileaflet mechanical valve is safe and effective, even over 30 years.

Thromboembolic events, major bleeding and mortality in essential thrombocythaemia and polycythaemia vera-A matched nationwide population-based study.

Thromboembolic events and bleeding are known complications in essential thrombocythaemia (ET) and polycythaemia vera (PV). Using multiple Swedish health care registers, we assessed the rate of arterial and venous events, major bleeding, all-cause stroke and all-cause mortality in ET and PV compared to matched controls. For each patient with ET (n = 3141) and PV (n = 2604), five matched controls were randomly selected. In total, 327 and 405 arterial or venous events were seen in the group of ET and PV patients respectively. Compared to corresponding controls, the rate of venous thromboembolism, major bleeding and all-cause mortality per 100 treatment years was significantly increased among both ET (0.63, 0.79 and 3.70) and PV patients (0.94, 1.20 and 4.80). The PV patients also displayed a significantly higher rate of arterial events and all-cause stroke compared to controls. When dividing the cohort into age groups, we found a significantly higher rate of arterial and venous events in all age groups of PV patients, and the rate of all-cause mortality was significantly higher in both ET and PV patients in all ages above the age of 50. This study confirms that PV and ET are diseases truly marked by thromboembolic complications and bleeding.

Characteristics and outcome of patients with left atrial appendage closure in China: a single-center experience.

BACKGROUND: Clinical characteristics and long-term data on the safety and efficacy of LAAC in preventing cerebrovascular accident and thromboembolism among Chinese patients with non-valvular AF (NVAF) remain limited. METHODS: Data of consecutive NVAF patients who underwent LAAC at Beijing Anzhen Hospital, Capital Medical University, from June 1, 2014, to December 31, 2021, were collected and analyzed retrospectively. The primary effectiveness endpoint was the composite endpoint of stroke/transient ischemic attack, systemic embolism, and death from cardiovascular causes. The primary safety endpoint is the severe bleeding defined by the LAAC Munich consensus. RESULTS: Of the 222 patients enrolled, the mean age was 66.90 ± 9.62 years, with a majority being male (77.03%). Many patients are non-paroxysmal AF (71.19%) with a median duration of AF of 4.00 years. The mean CHA2DS2-VASc score was 3.78 ± 1.49, and the mean HAS-BLED score was 1.68 ± 0.86. Thromboembolic events (76.58%) were the most common indication for LAAC. The device, technical, and procedural success rates were 98.65%, 98.65%, and 93.69%, respectively. The anticoagulation continuation rate was 56.36%, 31.25%, and 22.60% at 3-, 6- and 12 months post-procedure, respectively. Throughout a mean 2.81 years of follow-up, the incidence of the primary efficacy endpoint was 4.27 per 100 patient-years, predominantly attributable to stroke/TIA (3.12 per 100 PYs). Five patients experienced major bleeding during the follow-up period. Post-procedure imaging revealed minimal complications, with only one substantial peri-device leak. Device-related thrombus occurred in 2.33% of patients, resolving with anticoagulation. CONCLUSION: The study demonstrates that LAAC is a safe and effective alternative option for Chinese patients with AF, with a high success rate, few complications as well as fewer long-term adverse outcome events.

Risk of chronic thromboembolic pulmonary hypertension after splenectomy.

OBJECTIVES: The purpose of the clinical study was to evaluate the risk of chronic thromboembolic pulmonary hypertension (CTEPH) after splenectomy and to analyze some biochemical and coagulation parameters. BACKGROUND: CTEPH caused by incomplete resolution of thromboemboli and irreversible remodeling of the pulmonary arteries is a progressive, and without treatment a fatal disease. Although the definite etiopathophysiology is not quite perfectly researched, numerous clinical conditions associated with CTEPH as history of pulmonary embolism, infected ventriculoatrial shunts or permanent intravascular devices, high-dose thyroid hormone replacement, malignancy and chronic inflammatory diseases, including osteomyelitis, inflammatory bowel diseases, are well accepted. These factors also include splenectomy. METHODS: We performed a prospective follow-up of patients after splenectomy in the period of 5 years (2017-2022). The study population consisted of 62 adult post-splenectomy patients, who were divided into 3 groups based on the cause of the splenectomy - trauma, haematologic diseases, and others. The study population was analyzed in terms of gender, age, cause of splenectomy, blood group, clinical risk factors and thrombophilic conditions. Some basic haemocoagulation parameters and selected coagulation and biochemical parameters were analyzed. All patients underwent screening echocardiography, symptomatic patients repeatedly. In the presence of pulmonary hypertension (PH) unexplained by other diseases, patients underwent ventilation/perfusion lung scan performed to confirm/exclude perfusion defects typical for CTEPH. If PH and perfusion defects persisted despite effective 3-month anticoagulation therapy, patients underwent right heart catheterization to confirm/exclude CTEPH. RESULTS: The study confirmed a higher incidence of CTEPH after splenectomy compared to published data, the 5-year cumulative incidence was 3.2 %. Other detected clinical risk factors did not affect the incidence of thromboembolism/CTEPH after splenectomy. In our study, the strongest factor in terms of the incidence of thromboembolism/CTEPH after splenectomy was the presence of a thrombophilia detected before the screening echocardiography. Tested haemocoagulation and biochemical parameters in small patient subgroup had no impact on the incidence of thromboembolism/CTEPH - however, the limiting factor was a small patient subgroup. CONCLUSION: The results of the study suggest that the incidence of thromboembolism after splenectomy was consistent with the present data, but the incidence of CTEPH after splenectomy was significantly higher. This suggests that post-splenectomy condition may be an independent risk factor for CTEPH and may imply different management of these patients in the future (Tab. 5, Ref. 18).

Fibrillatory wave amplitude and thromboembolic risk in non-anticoagulated patients with atrial fibrillation.

BACKGROUND: The benefit of oral anticoagulation in atrial fibrillation (AF) is well established for patients at elevated stroke risk, but less clear for those at intermediate risk. We investigated whether analysis of electrocardiogram (ECG) derived fibrillatory waves (F-waves) could help identify patients at risk for stroke and systemic embolism (SSE). METHODS: The Finnish Cardioversion (FinCV) study included patients not on permanent anticoagulation therapy who underwent cardioversion for an acute AF episode. We identified 739 individuals with a valid ECG and complete follow-up data. The maximum amplitudes of the F-waves in leads II and V1 were manually measured from the pre-procedure ECG. Patients were categorized into fine and coarse F-wave groups. The optimal lead and amplitude threshold for grouping were found in an events per person-years analysis. SSE were identified from the patient medical records until either anticoagulation was prescribed, AF was deemed chronic, the patient had deceased, or the end of follow-up. RESULTS: Overall 37 (5.0%) patients suffered SSE during the median follow-up time of 5.4 years (1.9-10.8). Measured from lead V1 the SSE rates per 100 person-years were 1.5 and 0.7 in fine and coarse F-wave groups, respectively. Fine F-waves were observed in 112 (15.2%). Baseline characteristics were similar between the groups. Fine F-wave predicted SSE in a competing risk analysis (SHR 2.34, 95%CI 1.12-4.87, p = .023). Analyses from lead II did not provide significant results. CONCLUSION: Electrocardiographic F-wave amplitude may provide additional information on stroke risk in patients with paroxysmal AF and borderline indications or contraindications for anticoagulation.

Cerebral thromboembolic complications during cerebral angiography and their risk factors in different subgroups: Analysis of 2,457 procedures.

PURPOSE: Diagnostic cerebral digital subtraction angiography (DSA) is an invasive examination that involves catheterization of the major supra-aortic arterial trunks and evaluation of intracranial vessels for diagnostic purposes. Although considered the gold standard method for investigating cerebrovascular diseases, DSA carries measurable and potentially serious complication rates. This report describes the frequency of neurological and non-neurological complications of DSA performed in five hospitals in the state of São Paulo, Brazil, and analyzes them in different disease subgroups. It has a special focus on thromboembolic cerebral complications. METHODS: We retrospectively reviewed clinical records of all adult patients who underwent DSAs between January 2019 and December 2022. Demographic variables, DSA reports, CT/MRI reports, and clinical follow-up notes were reviewed. RESULTS: Twenty-four patients experienced some type of complication among 2,457 diagnostic DSAs (0.97%). Thromboembolic complications were recorded in 9 patients (0.36%), and access site hematomas larger than 5 cm were registered in six patients (0.24%). There was a statistical trend for thromboembolic complications in patients with cervical and/or intracranial atherosclerosis (p = 0.07), but age was not associated with them (p = 0.93). Patients who received heparin had lower rates of embolic complications than those who did not receive it, but there was no statistically significant difference (p = 0.17). Intravenous administration of heparin showed a trend toward significance with groin hematoma (p = 0.10). CONCLUSION: Diagnostic catheter DSAs have low complication rates.

Prevalence of Guideline-Discordant Aspirin Use and Associated Adverse Events in Patients on Warfarin for Mechanical Valve Replacement.

BACKGROUND: For patients on warfarin for mechanical heart valve replacement, the 2020 American College of Cardiology and American Heart Association Guidelines recommend only adding aspirin in patients with a specific indication for antiplatelet therapy. This contrasts with prior guidelines, which recommended concomitant aspirin therapy. We sought to assess the prevalence of guideline-discordant aspirin use among patients on warfarin for mechanical heart valve replacement and to compare adverse event rates among patients with and without concomitant aspirin. METHODS: Patients on warfarin for mechanical heart valve replacement were identified from the Michigan Anticoagulation Quality Improvement Initiative registry. Patients with myocardial infarction, percutaneous coronary intervention, or coronary artery bypass within the past 12 months were excluded. Patients were divided into 2 groups based on aspirin use. Patient characteristics and bleeding and thromboembolic outcomes were compared. RESULTS: Four hundred forty-four patients met the inclusion criteria, with 341 (76.8%) on concomitant aspirin. The aspirin group was older (50.6 vs 46.3 years, P = .028) and had more hypertension (57.8% vs 46.6%, P = .046) but other patient characteristics were similar. The aspirin group had a higher rate of bleeding events (28.3 vs 13.3 per 100 patient-years, P < .001) and bleed-related emergency department visits (11.8 vs 2.9 per 100 patient-years, P = .001) compared with the non-aspirin group. There was no observed difference in rates of ischemic stroke (0.56 vs 0.48 per 100 patient-years, P = .89). CONCLUSIONS: A significant proportion of patients on warfarin for mechanical heart valve replacement are on guideline-discordant aspirin. Aspirin deprescribing in select patients may safely reduce bleeding events.

Thromboembolic events in burn patients: An analysis of risk factors and different anticoagulants.

BACKGROUND: Burn patients are in a state of activated coagulation, putting them at risk for thromboembolic events. Additionally, certain patient-related factors are associated with an increased risk of thrombus formation. This study aimed to evaluate the incidence of thromboembolic events and identify potential risk factors, including patient characteristics, surgical treatment, anticoagulation strategies, and laboratory parameters. METHODS: A single-centre retrospective cohort study was conducted on all patients with burns treated between 2002 and 2020. Medical reports of patients with and without thromboembolic events were descriptively analysed. The association of time to thromboembolic events with total body surface area (TBSA) was assessed by cause-specific Cox models adjusted for different covariates. The association of time to thromboembolic events with type and dosage of anticoagulants was assessed using a cause-specific Cox proportional hazards model with time-dependent covariates, applied to a matched subset of patients. RESULTS: The incidence of thromboembolic events was 8.1% in a cohort of 642 patients. We found a statistically significant increase in the hazard for thromboembolic events by a factor of 1.02 (95% CI 1.00 to 1.03; P ≤ 0.05) per percent increase in TBSA. We identified former alcohol abuse (HR=2.54, CI 1.33 to 4.84, P = 0.005) and higher body mass index (HR=1.06, 95% CI 1.00 to 1.12, P = 0.046) as potential risk factors for the development of thromboembolic events. We further noted inadequate median anti-Factor-X activity levels and elevated C-reactive protein and procalcitonin levels at the time of the event. CONCLUSION: Our results showed a moderate risk of thromboembolic events among burn patients, underlining the importance of close monitoring with regard to thrombus formation. In particular, patients with higher TBSA, alcohol abuse and BMI may be evaluated more regularly for thromboembolic events. Anti-Factor-X activity levels should be determined regularly and therapy should be adjusted if necessary.

Net Clinical Benefit of Oral Anticoagulation Among Frail Patients With Atrial Fibrillation: Nationwide Cohort Study.

BACKGROUND: Frail people with atrial fibrillation are often undertreated with oral anticoagulants (OACs), and evidence for the net clinical benefit (NCB) of OAC is sparse. We, therefore, examined the risk of thromboembolic events, major bleeding, and NCB of anticoagulation treatment. METHODS: This was a nationwide cohort study including frail patients aged with incident atrial fibrillation between 2013 and 2018. Patients were categorized according to OAC treatment exposure. One-year risks of thromboembolic events and major bleeding were ascertained where death was treated as a competing risk. The NCB of anticoagulation was assessed by a bivariate trade-off between thromboembolism and bleeding. RESULTS: We identified 36 223 frail patients with atrial fibrillation (median age, 79 years; 50.5% female), of whom 61.8% started OAC therapy, while 38.2% were untreated despite indication for stroke prevention. At 1 year, the risk of thromboembolic events was 2.1% (95% CI, 1.8%-2.3%) among patients not receiving OAC versus 1.5% (95% CI, 1.4%-1.7%) in patients with OAC. The bleeding risk was 3.2% (95% CI, 2.9%-3.5%) among patients without OAC versus 3.5% (95% CI, 3.2%-3.8%) among anticoagulated patients. The NCB was 0.70% (95% CI, 0.32%-1.08%), suggesting a benefit of OAC treatment; however, the NCB declined with age and increasing frailty and was lowest among patients >75 years of age or with high frailty level. CONCLUSIONS: Frail patients with atrial fibrillation are often untreated with OAC in routine clinical care despite an indication for stroke prevention. The NCB balancing thromboembolic events and major bleeding was in favor of anticoagulation but decreased with advancing age and increasing frailty.

Thromboembolic Events With the Woven Endobridge Device: Incidence, Predictive Factors, and Management.

BACKGROUND AND OBJECTIVES: The Woven EndoBridge (WEB) device has been increasingly used to treat wide-neck aneurysms showing a safe and effective profile, but a relatively high number of thromboembolic events (TEEs) have been reported with such treatment. We aimed to evaluate the incidence and management of TEEs and possible predictive factors related to WEB embolization of ruptured and unruptured intracranial aneurysms. METHODS: A single-center database with consecutive aneurysms treated with a WEB device between July 2012 and May 2022 was reviewed for intraoperative and delayed TEEs. Univariate and multivariable analyses were used to determine factors associated with TEEs. RESULTS: A total of 266 independent aneurysms were treated with WEB devices in 245 patients (mean age 55.78 ± 11.64 years, 169 (63.5%) females, 80 (30%) ruptured). The overall rate of TEEs is 13% (35/266), including 8.7% intraoperative. Symptomatic TEEs with clinical sequelae at a 3-month follow-up are reported to be 2.6% (7/266) with no TEE-related mortality. Both the replacement of a WEB device during the procedure (adjusted odds ratio = 2.61, 95% CI 1.24-5.49; P = .01) and ruptured aneurysms (adjusted odds ratio = 2.74, 95% CI 1.31-5.7; P = .007) were independent predictors of TEEs. A case-by-case management of intraprocedural TEE is also presented; tirofiban was successfully used in most cases of this cohort. CONCLUSION: In this study, we demonstrated that ruptured aneurysms and WEB device replacement during the procedure were independent predictive factors for TEEs. As a result, making the correct choice of WEB is crucial for improving treatment outcomes. Moreover, with proper medical management of TEEs, minimal morbidity and no mortality could be achieved, which reinforces the safety of the technique.

Mitigating the Risk of Tofacitinib-induced Adverse Events in the Elderly Population with Ulcerative Colitis.

BACKGROUND AND AIMS: Older patients with ulcerative colitis treated with tofacitinib are at risk for major cardiovascular events, thromboembolism, herpes zoster, and malignancies and, accordingly, its use is limited by the regulatory authorities. The aim of the present study was to evaluate the occurrence of adverse events and potential preventive measures. METHODS: We retrospectively evaluated patients treated with tofacitinib, divided into two groups according to comorbidities and age. Patient- and disease-related variables were recorded [primary non-response, loss of response, and persistence], together with deviations from the recommended induction regimen, ie, dose reduction, and concomitant treatments with anti-thrombotic therapy. RESULTS: The age-adjusted Charlson comorbidity index of Group 1 [n = 30] was ≥2 and that of Group 2 [n = 37] was ≤ 1. No differences were observed for primary or secondary treatment failures. Both groups achieved comparable steroid-free remission rates at 12 months [53% and 46%, respectively]. Herpes zoster occurred in two patients per group, and no more cases occurred after strict recombinant zoster vaccination. No major cardiovascular event or thromboembolism was registered. Half of patients in Group 1 were treated with a reduced induction dose of 5 mg twice daily and 47% were on concomitant anti-thrombotic therapy. Malignancies were registered in two patients from Group 1 and one patient from Group 2. CONCLUSIONS: Modulation of induction dose and anti-thrombotic therapy may have contributed to prevent cardiological events and thromboembolism. The introduction of zoster vaccine virtually eliminated zoster risk after the first cases. Potential malignancies deserve a careful work-up of older patients before treatment start.

Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.

BACKGROUND: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). METHODS: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min-1·1.73 m-2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. RESULTS: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61). CONCLUSIONS: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications. REGISTRATION: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).