Elevated Risk Of Thromboembolism Research Articles

Favorable safety profile of NOAC therapy in patients after tricuspid transcatheter edge-to-edge repair.

Transcatheter edge-to-edge repair for severe tricuspid regurgitation (TR) is a new treatment option (t-TEER). Data on optimal antithrombotic therapy after t-TEER in patients with an indication for anticoagulation are scarce and evidence-based guideline recommendations are lacking. We sought to investigate efficacy and safety of novel oral anticoagulation (NOAC) and vitamin-K-antagonists (VKA) in patients undergoing t-TEER. Among 78 consecutive patients with t-TEER of severe TR, 69 patients were identified with concomitant indication for oral anticoagulation. Outcomes of these patients treated with NOAC or VKA were compared over a median follow-up period of 327 (177-460) days. Despite elevated thromboembolic and bleeding risk scores (CHA2DS2-VASc 4.2 ± 1.1, HEMORR2HAGES 3.0 ± 1.0 and HAS-BLED 2.1 ± 0.8), only one major bleeding incidence occurred under NOAC therapy. The risk for overall (NOAC 8% vs. VKA group 26%, p = 0.044) and major bleeding events (NOAC 2% vs. VKA 21%, p = 0.010) was significantly lower in the NOAC compared to the VKA group. No significant difference was found between NOAC and VKA treatment in terms of mortality (NOAC 18% vs. VKA 16%, p = 0.865) or the combined endpoint of death, heart failure hospitalization, stroke, embolism, thrombosis, myocardial infarction, and severe bleeding (NOAC 48% vs. VKA 42%, p = 0.801). A comparison between apixaban (n = 27) and rivaroxaban (n = 16) treated patients revealed no significant differences between NOAC substances (all bleeding events apixaban 7% vs. rivaroxaban 13%, p = 0.638). Results of this study indicate that NOACs may offer a favorable risk-benefit profile for patients with concomitant indication for anticoagulation therapy following t-TEER.

Apixaban versus warfarin for primary thromboprophylaxis in patients with multiple myeloma undergoing immunomodulatory treatment.

7548 Background: Immunomodulatory drugs (IMiDs) have been demonstrated to improve clinical outcomes in patients with multiple myeloma (MM), but are associated with an elevated risk of thromboembolism. Existing guidelines recommend low-dose direct oral anticoagulants as an alternative to warfarin for primary thromboprophylaxis in MM. However, the data comparing these two therapies are limited. We aim to compare the efficacy and safety of apixaban versus warfarin in patients with MM undergoing IMiD treatment. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included adult patients with MM who underwent IMiD treatment. Patients treated with apixaban were matched in a 1:1 ratio to those treated with warfarin using clinical variables a priori. The primary safety outcomes included all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding, while the primary efficacy outcomes included thromboembolic events including pulmonary embolism, deep venous thrombosis, and ischemic stroke within a 3-year period following IMiDs initiation. Results: We identified 448 patients on apixaban who were matched to patients on warfarin. In a Cox proportional hazard analysis, apixaban was associated with a 30% lower risk of all-cause mortality compared to warfarin (Hazard ratio (HR), 0.70 [95% CI: 0.56-0.88]).There was a tendency toward a reduced risk of gastrointestinal bleeding in patients treated with apixaban compared to warfarin (HR, 0.58 [95% CI: 0.31-1.08], log-rank p = 0.083). The risk of intracranial hemorrhage was similar between the two groups.The risks of thromboembolic events including pulmonary embolism, deep venous thrombosis, and ischemic stroke were comparable between the apixaban and warfarin cohorts. Conclusions: Apixaban was associated with a lower risk of all-cause mortality and a comparable risk of bleeding and thromboembolism compared with warfarin among MM patients undergoing immunomodulatory treatment. [Table: see text]

Hyperhomocysteinemia is associated with the risk of venous thromboembolism in patients with mental illness: a case-control study.

The risk of venous thromboembolism in patients with mental illness has been insufficiently addressed. This study aimed to assess the correlation between hyperhomocysteinemia and venous thromboembolism prevalence among this population. Patients with a diagnosis of mental illness and concurrent venous thromboembolism, admitted to Sir Run Run Shaw Hospital at Zhejiang University School of Medicine between January 2014 and December 2021, were included in the venous thromboembolism group. The control group, approximately twice the size, comprised individuals with mental illness but without venous thromboembolism. Basic clinical data were gathered for both cohorts. In psychiatric patients, elevated D-dimer levels(OR=5.60,95% CI 3.28-10.00), hyperhomocysteinemia (OR=2.37,95% CI 1.10-5.14), and hyperprolactinemia(OR= 2.68,95% CI 1.12-6.42)were significant risk factors for venous thromboembolism. According to further subgroup analyses, hyperhomocysteinemia is a significant risk factor associated with pulmonary embolism, with an OR of 5.08 (95% CI 1.20-21.48). An interaction effect between gender and homocysteine level was found, with a p-interaction of 0.022.A subsequent analysis confirmed the association between hyperhomocysteinemia and venous thromboembolism in female psychiatric patients, with an OR of 3.34 (95% CI 1.68-6.65), indicating that hyperhomocysteinemia is a significant risk factor for venous thromboembolism in women. Patients with psychiatric disorders were found to have an elevated risk of venous thromboembolism, which was associated with increased levels of D-dimer, hyperprolactinemia, and hyperhomocysteinemia. A strong correlation between hyperhomocysteinemia and pulmonary embolism was identified in patients with mental illnesses. Furthermore, the study revealed that female psychiatric patients with hyperhomocysteinemia constituted a high-risk group for venous thromboembolism. This finding holds significant clinical implications, suggesting that early preventative measures could be implemented for this high-risk population to reduce the incidence of thromboembolic events during hospitalization for psychiatric patients.

Comprehensive evaluation of genetic and acquired thrombophilia markers for an individualized prediction of clinical thrombosis in patients with lymphoma and multiple myeloma

Patients diagnosed with lymphoma or multiple myeloma are at elevated risk of venous thromboembolism (VTE). Optimum risk stratification and effective thromboprophylaxis can only be achieved through the development of a multiple-specific risk score that successfully captures all aspects of the heterogeneous prothrombotic environment existing in these patients. Our aim was to identify risk factors for thrombosis and suggest an improved tool combining clinical data, thrombo-inflammatory biomarkers and genetic (Thrombo inCode® test) variables for predicting thrombotic risk in patients with lymphoma and multiple myeloma. A prospective longitudinal study was conducted on newly-diagnosed lymphoma and multiple myeloma patients who presented at our institution between February 2020 and January 2021. The study included 47 patients with lymphoma and 16 patients with multiple myeloma. We performed a follow-up of 1 year or until September 2021. The incidence of venous thrombosis and associated risk factors were analysed, including the genetic Thrombo inCode® test. Khorana and ThroLy scores for lymphoma patients and IMPEDE VTE score for myeloma patients were calculated. At a median follow-up of 9.1 months, VTE incidence was 9.5% (6/63), with 4 and 2 patients with lymphoma and myeloma who developed the events, respectively. Univariate analysis showed that the incidence of thrombosis was significantly higher in patients with ECOG ≥ 2 and prior immobility. Median factor VIII levels were significantly higher in patients with thrombosis (with increased values in all of them). Moreover, there was a trend in genetic variant rs5985 (factor XIII) as a protective factor, and a trend to higher thrombotic risk in patients with factor V Leiden, rs2232698 variant (serpinA10), low total protein S activity, elevated D-dimer, aggressive lymphoma and treatment with dexamethasone. The results of our study demonstrate promise for the potential use of widely accessible markers to increase precision in risk prediction for VTE in patients with lymphoma and multiple myeloma, particularly ECOG ≥ 2, immobility and higher factor VIII levels, as well as lymphoma aggressiveness, treatment with dexamethasone and the haemostatic biomarkers D-dimer and total protein S activity. Additionally, genetic variants factor V Leiden, serpinA10 rs2232698 and factor XIII-A Val34Leu warrant further investigation for use in the research setting.Graphical

Left atrial appendage filling defect in exclusive early-phase scanning of dual-phase cardiac computed tomography: An indicator for elevated thromboembolic risk.

Dual-phase cardiac computed tomography (CCT) has been applied to detect left atrial appendage (LAA) thrombosis, which is characterized as the presence of left atrial appendage filling defects (LAADF) in both early- and delayed-phase scanning. However, the clinical implication of LAAFD in exclusive early-phase scanning (LAAFD-EEpS) of CCT in patients with atrial fibrillation (AF) is unclear. The baseline clinical data and dual-phase CCT findings in 1183 AF patients (62.1 ± 11.6 years, 59.9% male) was collected and analyzed. A further analysis of CCT and transesophageal echocardiography (TEE) data (within 5 days) in a subgroup of 687 patients was performed. LAAFD-EEpS was defined as LAAFD present in early-phase and absent in delayed-phase scanning of dual-phase CCT. A total of 133 (11.2%) patients were detected with LAAFD-EEpS. Patients with LAAFD-EEpS had a higher prevalence of ischemic stroke or transient ischemic attack (TIA) (p < 0.001) and a higher predefined thromboembolic risk (p < 0.001). In multivariate analysis, a history of ischemic stroke or TIA was independently associated with LAAFD-EEpS (odds ratio [OR] 11.412, 95% confidence interval [CI] 6.561-19.851, p < 0.001). When spontaneous echo contrast in TEE was used as the reference standard, the sensitivity, specificity, positive predictive value, and negative predictive value of LAAFD-EEpS was 77.0% (95% CI 66.5-87.6%), 89.0% (95% CI 86.5-91.4%), 40.5% (95% CI 31.6-49.5%), 97.5% (96.3-98.8%), respectively. In AF patients, LAAFD-EEpS is not an uncommon finding in dual-phase CCT scanning, and is associated with elevated thromboembolic risk.

Risk factors for venous thromboembolism in patients with pneumonia in the pre-COVID-19 era: a meta-analysis and systematic review.

Elevated risk of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) pneumonia has been recognized, while the risk factors associated with VTE in patients with non-COVID-19 pneumonia remain to be defined. This study aimed to conduct a meta-analysis and systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify potential risk factors for VTE in patients with pneumonia from the pre-COVID-19 era. PubMed, EMBASE, and Cochrane Library were searched. Two reviewers performed screening, full-text review, and extraction. Risk factors and odds ratio (OR) were estimated. Of 595 articles identified, six studies were included. Pooled analysis suggested that age ≥60 years [OR =2.75, 95% confidence interval (CI): 2.55-2.97, P<0.001], mechanical ventilation (MV) (OR =9.48, 95% CI: 8.24-10.91, P<0.001), hypertension (OR =1.41, 95% CI: 1.09-1.83, P=0.010), diabetes (OR =1.49, 95% CI: 1.36-1.64, P<0.001), heart failure (OR =3.15, 95% CI: 1.05-9.41, P=0.040) and cancer (OR =2.86, 95% CI: 2.07-3.95, P<0.001) were associated with higher risk for deep vein thrombosis in patients with pneumonia. While age ≥60 years (OR =2.46, 95% CI: 2.21-2.73, P<0.001), bacterial pneumonia (OR =3.80, 95% CI: 1.65-8.73, P=0.002), hyperlipidemia (OR =1.55, 95% CI: 1.00-2.41, P=0.049), heart failure (OR =2.70, 95% CI: 2.05-3.56, P<0.001), chronic obstructive pulmonary disease (OR =4.73, 95% CI: 3.11-7.17, P<0.001) and cancer (OR =2.90, 95% CI: 2.39-3.53, P<0.001) were risk factors for pulmonary embolism in patients with pneumonia. Patients with non-COVID-19 pneumonia, particularly those with advanced age, MV, cardiovascular comorbidities or cancer, warrant individualized management during hospitalization. Our findings could contribute to refining risk prediction models and further risk stratification for VTE in patients with pneumonia in clinical practice.

Gaps in guideline-recommended anticoagulation in patients with atrial fibrillation and elevated thromboembolic risk within an integrated healthcare delivery system

BackgroundAtrial Fibrillation (AF) is the leading cause of stroke, which can be reduced by 70% with appropriate oral anticoagulation (OAC) therapy. Nationally, appropriate anticoagulation rates for patients with AF with elevated thromboembolic risk are as low as 50% even across the highest stroke risk cohorts. This study aims to evaluate the variability of appropriate anticoagulation rates among patients by sex, ethnicity, and socioeconomic status within the Kaiser Permanente Mid-Atlantic States (KPMAS).MethodsThis retrospective study investigated 9513 patients in KPMAS’s AF registry with CHADS2 score ≥ 2 over a 6-month period in 2021.ResultsAppropriately anticoagulated patients had higher rates of diabetes, prior stroke, and congestive heart failure than patients who were not appropriately anticoagulated. There were no significant differences in anticoagulation rates between males and females (71.8% vs. 71.6%%, [OR] 1.01; 95% CI, 0.93-1.11; P = .76) nor by SES-SVI quartiles. There was a statistically significant difference between Black and White patients (70.8% vs. 73.1%, P = .03) and Asian and White patients (68.3% vs. 71.6%, P = .005). After adjusting for CHADS2, this difference persisted for Black and White participants with CHADS2 scores of ≤3 (62.6% vs. 70.6%, P < .001) and for Asian and White participants with CHADS2 scores > 5 (68.0% vs. 79.3%, P < .001).ConclusionsBlack and Asian patients may have differing rates of appropriate anticoagulation when compared with White patients. Characterizing such disparities is the first step towards addressing treatment gaps in AF.

Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis.

Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.

Comparison of Medical and Mental Health Sequelae Following Hospitalization for COVID-19, Influenza, and Sepsis

People who survive hospitalization for COVID-19 are at risk for developing new cardiovascular, neurological, mental health, and inflammatory autoimmune conditions. It is unclear how posthospitalization risks for COVID-19 compare with those for other serious infectious illnesses. To compare risks of incident cardiovascular, neurological, and mental health conditions and rheumatoid arthritis in 1 year following COVID-19 hospitalization against 3 comparator groups: prepandemic hospitalization for influenza and hospitalization for sepsis before and during the COVID-19 pandemic. This population-based cohort study included all adults hospitalized for COVID-19 between April 1, 2020, and October 31, 2021, historical comparator groups of people hospitalized for influenza or sepsis, and a contemporary comparator group of people hospitalized for sepsis in Ontario, Canada. Hospitalization for COVID-19, influenza, or sepsis. New occurrence of 13 prespecified conditions, including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis, within 1 year of hospitalization. Of 379 366 included adults (median [IQR] age, 75 [63-85] years; 54% female), there were 26 499 people who survived hospitalization for COVID-19, 299 989 historical controls (17 516 for influenza and 282 473 for sepsis), and 52 878 contemporary controls hospitalized for sepsis. Hospitalization for COVID-19 was associated with an increased 1-year risk of venous thromboembolic disease compared with influenza (adjusted hazard ratio, 1.77; 95% CI, 1.36-2.31) but with no increased risks of developing selected ischemic and nonischemic cerebrovascular and cardiovascular disorders, neurological disorders, rheumatoid arthritis, or mental health conditions compared with influenza or sepsis cohorts. In this cohort study, apart from an elevated risk of venous thromboembolism within 1 year, the burden of postacute medical and mental health conditions among those who survived hospitalization for COVID-19 was comparable with other acute infectious illnesses. This suggests that many of the postacute consequences of COVID-19 may be related to the severity of infectious illness necessitating hospitalization rather than being direct consequences of infection with SARS-CoV-2.

Re-evaluation of the risk of venous thromboembolism after COVID-19 vaccination using haematological criteria

An elevated risk of venous thromboembolism (VTE) following a first dose of the ChAdOx1 adenovirus-vectored vaccine was found in a national epidemiological study in England using routine discharge diagnosis codes. Separately, the syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) was identified using haematological criteria based on presence of thrombocytopenia, significantly elevated D-dimers and development of anti-PF4 antibodies. To re-evaluate risk estimates using haematological criteria, we obtained the haematology results for hospital admitted patients aged 18–64 years in 43 National Health Service trusts in England who were included in the national epidemiological study. Diagnoses were confirmed and haematological parameters obtained from local records without knowledge of vaccination status. The haematological parameters in patients admitted for a confirmed VTE following ChAdOx1 or BNT162b2 mRNA vaccination were then compared with those in a randomly selected 40% sample of unvaccinated patients with VTE. Overall, 12 (14%) of the 84 vaccinated cases had a diagnosis compatible with VITT, 11 after a first dose of ChAdOx1 and one after a first dose of BNT162b2. Thrombocytopenia (platelet count <150 × 109/L) occurred in 17 vaccinated (20%) and 4 (4%) of 108 unvaccinated patients, with all 6 cases of severe thrombocytopenia (<50 × 109/L) occurring within 42 days of a first dose of ChAdOx1. The attributable risk estimates for a cerebral venous thrombosis (CVT) or other VTE with thrombocytopenia after a first dose of ChAdOx1 vaccine were 2.82 and 9.62 per million doses respectively. However, elevated risks were also found after a first dose of ChAdOx1 for VTE without thrombocytopenia with relative incidences for CVT and other VTE of 2.67 (1.77–3.77) and 1.93 (1.57–2.35) respectively. While we identified a distinct population with features of VITT within 42 days of receiving ChAdOx1 vaccination, confirming current diagnostic criteria, we also found evidence of an increased risk of a VTE without thrombocytopenia after ChAdOx1 vaccine.

Non-vitamin k oral antagonists versus aspirin for primary thromboprophylaxis in patients with multiple myeloma on outpatient chemotherapy: A systematic review and meta-analysis.

e20041 Background: Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased in patients receiving immunomodulatory drugs (IMiDs). Current guidelines suggest that non-vitamin K oral anticoagulants (NOACs) may be an alternative to low-dose aspirin (ASA) for primary thromboprophylaxis in this population. However, there is limited data comparing these two antithrombotic therapies among MM patients undergoing treatment with IMiDs. Methods: We performed a systematic review and meta-analysis to compare NOACs with ASA for primary thromboprophylaxis in individuals with newly-diagnosed or relapsed/refractory MM undergoing outpatient chemotherapy with an IMiD-based regimen. PubMed, Cochrane, and EMBASE were systematically searched from inception to January 2023. Observational studies and randomized controlled trials were included when comparing NOACs versus aspirin for thrombotic and hemorrhagic outcomes. Statistical analysis was performed with Review Manager 5.4.1. Results: We included 10 randomized controlled trials and observational studies comprising 1026 MM patients who underwent primary thromboprophylaxis with NOACs (33%) or ASA (67%). Thromboprophylaxis with NOACs was associated with a significantly lower incidence of VTE compared with ASA (OR, 0.33; 95% CI, 0.16-0.68; p &lt; 0.001; I² = 0%). Each group had one major bleeding event, with no statistically significant difference between NOACs and ASA (OR, 1.35; 95% CI, 0.05-35.51; p = 0.86; I² = 51%). Similarly, clinically relevant non-major bleeding (OR, 0.56; 95% CI, 0.12-2.70; p = 0.47; I² = 0%) and minor bleeding (OR 1.48; 95% CI: 0.42-5.24; p = 0.54; I² = 0%) event rates did not differ significantly between groups. Conclusions: These findings suggest that NOACs may be superior to ASA for VTE prophylaxis among MM patients receiving IMiD-based chemotherapy, with no significant difference in the overall bleeding risk between the two groups.

Immunothrombosis and COVID-19 ‒ a nested post-hoc analysis from a 3186 patient cohort in a Latin American public reference hospital

ObjectiveCOVID-19 is associated with an elevated risk of thromboembolism and excess mortality. Difficulties with best anticoagulation practices and their implementation motivated the current analysis of COVID-19 patients who developed Venous Thromboembolism (VTE). MethodThis is a post-hoc analysis of a COVID-19 cohort, described in an economic study already published. The authors analyzed a subset of patients with confirmed VTE. We described the characteristics of the cohort, such as demographics, clinical status, and laboratory results. We tested differences amid two subgroups of patients, those with VTE or not, with the competitive risk Fine and Gray model. ResultsOut of 3186 adult patients with COVID-19, 245 (7.7%) were diagnosed with VTE, 174 (5.4%) of them during admission to the hospital. Four (2.3% of these 174) did not receive prophylactic anticoagulation and 19 (11%) discontinued anticoagulation for at least 3 days, resulting in 170 analyzed. During the first week of hospitalization, the laboratory most altered results were C-reactive protein and D-dimer. Patients with VTE were more critical, had a higher mortality rate, worse SOFA score, and, on average, 50% longer hospital stay. ConclusionProven VTE incidence in this severe COVID-19 cohort was 7.7%, despite 87% of them complying completely with VTE prophylaxis. The clinician must be aware of the diagnosis of VTE in COVID-19, even in patients receiving proper prophylaxis.

Clinical effectiveness and safety of aspirin and other anticoagulants for venous thromboembolism prophylaxis after major orthopedic surgery: a systematic review and meta-analysis of randomized clinical trials.

Patients undergoing major orthopedic surgeries, such as total hip replacement (THR), total knee replacement (TKR), and trauma surgery, are at an elevated risk of venous thromboembolism (VTE), causing significant morbidity and mortality. Previous studies have investigated aspirin as a thromboprophylactic agent for arthroplasty, besides trauma surgery. Therefore, we sought to analyze the efficacy of aspirin compared to that of other anticoagulants for VTE prophylaxis in patients undergoing major orthopedic surgeries. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered with the PROSPERO register. Randomized controlled trials that investigated the use of aspirin for thromboprophylaxis in major orthopedic lower limb surgeries were included and analyzed. Quality analysis of the literature and level of evidence were assessed. The primary clinical outcome was VTE. Secondary clinical outcomes included mortality, bleeding events, and wound complications. Eight high-quality studies with level 2 evidence (published within 2006-2021) were included, comprising 6220 patients. The incidence of VTE with aspirin was not found to be more significant than other anticoagulants (risk ratio (RR) = 1.18, 95% CI: 0.89-1.58, P = 0.25). Regarding secondary outcomes, there were no significant differences between aspirin and other anticoagulants (mortality (RR = 1.40, 95% CI: 0.27-7.23, P = 0.69), bleeding events (RR = 0.89, 95% CI: 0.57-1.39, P = 0.61), or wound complications (RR = 0.64, 95% CI: 0.30-1.35, P = 0.24)). The current meta-analysis did not show any difference between aspirin and other anticoagulants as thromboprophylactic agents in preventing VTE in patients who underwent major orthopedic surgeries.

Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis.

Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30–10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17–32.35), mucositis (RR 3.18; 95% CI 1.52–6.65), hypomagnesemia (RR 20.10; 95% CI 5.92–68.21), and dehydration (RR 2.81; 95% CI 1.03–7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.

Long-Term Outcomes of Perioperative Versus Nonoperative Myocardial Infarction: A Danish Population-Based Cohort Study (2000-2016).

Perioperative myocardial infarction is a serious cardiovascular complication of noncardiac surgery. The clinical course of perioperative myocardial infarction, other than all-cause mortality, is largely unknown. We examined long-term fatal and nonfatal outcomes of perioperative myocardial infarction compared with nonoperative myocardial infarction. We conducted a population-based cohort study of first-time myocardial infarction in Denmark from 2000 to 2016. We calculated cumulative incidence of all-cause mortality, cardiac mortality, recurrent myocardial infarction, heart failure, stroke, venous thromboembolism, acute kidney injury, and kidney failure with replacement therapy. We computed 5-year risk ratios adjusted for age, sex, year of diagnosis, educational level, and comorbidities. We identified 5068 patients with perioperative myocardial infarction and 137 862 patients with nonoperative myocardial infarction. The 5-year risk of all-cause mortality was 67.5% (95% CI, 66.1%-69.0%) for perioperative myocardial infarction patients and 38.0% (95% CI, 37.7%-38.3%) for nonoperative myocardial infarction patients. The adjusted risk ratio of all-cause mortality was 1.13 (95% CI, 1.11-1.16) at 5 years. After adjustment, we found no association between patients with perioperative myocardial infarction and 5-year cardiac mortality, recurrent myocardial infarction, heart failure, stroke, or kidney failure with replacement therapy when compared with nonoperative myocardial infarction patients. Perioperative myocardial infarction patients had a higher relative risk of venous thromboembolism (5-year risk ratio, 1.21 [95% CI, 1.01-1.46]) and acute kidney injury (5-year risk ratio, 1.37 [95% CI, 1.22-1.53]). Compared with nonoperative myocardial infarction patients, perioperative myocardial infarction patients had elevated risk of all-cause mortality, venous thromboembolism, and acute kidney failure. In addition to the myocardial infarction component of perioperative myocardial infarction, this poor prognosis seemed associated with the surgery or underlying comorbidities. These findings warrant further research on strategies to reduce the risk of perioperative myocardial infarction and on strategies to manage perioperative myocardial infarction.

Vascular access thrombosis among end-stage renal disease patients with acute COVID19 infection (a retrospective cohort study)

Background According to studies, coronavirus disease 2019 (COVID19) infection is linked to an elevated risk of venous thromboembolism (TE). The frequencies of overall COVID19 thrombotic events and the influence of TE on COVID19 mortality, however, are unknown. Although respiratory symptoms are the most common symptom of the disease, evidence is growing suggesting that it is linked to coagulation system malfunction, which puts patients at risk for venous and arterial TE and higher mortality as well. Materials and methods A retrospective cohort study was conducted on 50 end-stage renal disease patients on maintenance hemodialysis (25 patients with confirmed COVID19 infection and 25 patients without COVID19 infection) to determine the incidence of vascular access thrombosis among patients with COVID19 during a 3-month period. Risk factors for mortality and severity were considered as secondary outcomes. Patients with previous history of vascular access dysfunction were excluded from the study. Results In all, 24% of COVID19-positive patients (n=6) developed vascular access thrombosis during 3 months of follow-up while no one of the COVID19-negative patient developed access thrombosis. The incidence of vascular access thrombosis was statistically higher in the COVID19 positive group (p value &lt; 0.022). The incidence of vascular access thrombosis was significantly can u please add this part : increased in patients who had lymphopenia, elevated LDH, also it was more common in patients who needed mechanical ventilation and who had severe disease Conclusion The incidence of vascular access thrombosis was statistically higher in the COVID19 positive group (p value &lt; 0.022). The incidence of vascular access thrombosis was significantly can u please add this part: increased in patients who had lymphopenia, elevated LDH, also it was more common in patients who needed mechanical ventilation and who had severe disease.

ISCHEMIC PRIAPISM: A STARTLING THROMBOEMBOLIC COMPLICATION OF COVID-19

TYPE: Case Report TOPIC: Chest Infections INTRODUCTION: The coronavirus disease-2019 (COVID-19) is known to cause severe systemic inflammation leading to thrombotic complications. Deep vein venous thrombosis, pulmonary embolism and stroke are some of the most commonly reported. However, ischemic priapism has been rarely documented as a thromboembolic consequence. CASE PRESENTATION: A 39-year-old man with a history of hypertension and type 2 diabetes mellitus presented with a painful irreducible erection of six-hour duration. Physical exam revealed tachycardia and a tender, rigid penile shaft, with an engorged glans and corpus spongiosum. He denied prior episodes or penile trauma. Laboratory-work revealed an elevated D-Dimer and inflammatory markers, as well as a positive COVID PCR test. Further investigations showed no previous hematological diseases or medications with an elevated thromboembolic risk. He received epinephrine irrigation and cavernosal blood aspiration which resolved the priapism. Nonetheless, the erection recurred a few hours later and a heparin infusion was started. Despite being on heparin for 24 hours, the erection persisted, requiring surgical intervention via a corpora cavernosa - penis glans fistula. The erection resolved and he was discharged home. DISCUSSION: Priapism is a prolonged penile erection of more than four hours without sexual stimulation. Interestingly, COVID-19 induces thrombosis by the hypercoagulability, hyperviscosity, and endothelial dysfunction after the massive inflammatory response and free radical damage. Ischemic priapism is a medical emergency that prompts treatment with a-agonists and corporal blood aspiration if needed. Detumescence can be achieved surgically if the initial measures fail. CONCLUSIONS: This case highlights a rare complication of COVID-19. Early recognition and medical treatment can prevent irreversible complications. DISCLOSURE: Nothing to declare. KEYWORD: COVID-19 Ischemic Priapism

Atrial fibrillation and stroke risk of patients with hypertrophic cardiomyopathy in denmark from 2005-2018: a nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Internal funding: Herlev-Gentofte Cardiovascular Research Department. Background Hypertrophic cardiomyopathy (HCM) can be associated with serious complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms. Previous studies have suggested that HCM patients with AF have an elevated risk of thromboembolism and stroke compared to AF patients without HCM regardless of their CHA2DS2VASc score. Purpose To determine the risk of AF and stroke in HCM patients. Methods Through the Danish National Registers all patients aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM, AF, and stroke was investigated using multivariable Cox proportional-hazard analysis adjusted for gender, age, atrial fibrillation, ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease and hypertension. Cumulative incidence of AF and stroke was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account. Results A total of 3856 patients were included, 2060 (53,4%) were male and median age of 67,8 (IQR 56 and 77,8) years. During the study period, 384 (10%) patients were diagnosed with AF. The risk of AF was significantly lower in males (HR 0,72 (0,59–0,90), p-value = 0.003) and for patients below 60 years (HR 0,18 (0,12–0,27), p-value = &amp;lt;0.001). (Figure 1) 157 (4,1%) of the HCM patients developed stroke. The risk of developing stroke was significantly decreased for patients aged under 60 (HR 0,32 (0,2–0,52), p-value = &amp;lt;0.001). There was no increased risk of stroke comparing genders. Stroke risk was further analyzed in patients with known AF at time of inclusion, 656 (17%) in total. Compared to patients without AF and adjusted for age, gender and co-morbidities, there was no significant difference in stroke risk between these groups (HR 1.2 (0,81-1,76), p-value = 0.36). (Figure 2) Conclusion AF and stroke are common complications in HCM. Women are more susceptible to developing AF than men, and age over 60 at the time of diagnosis was associated with significantly higher risk of AF and stroke. HCM patients with previously known AF did not have a significantly elevated risk of stroke. More research will be needed to further explore these connections.

PO-718-03 IDENTIFYING AND CHARACTERIZING PATIENTS WITH ATRIAL FIBRILLATION AND ELEVATED THROMBOEMBOLIC RISK WHO ARE NOT APPROPRIATELY ANTICOAGULATED

Atrial fibrillation (AF) is the leading cause of stroke, which can be reduced by 70% with appropriate use of anticoagulation therapy. Nationally, appropriate anticoagulation rates for patients with AF with elevated thromboembolic risk are as low as 50% even across the highest CHADS2VASC score cohorts. Understanding anticoagulation fallout rates among gender, ethnicity, and socioeconomic status is an important first step towards decreasing the risk of thromboembolic events. This study aims to evaluate the variability of appropriate anticoagulation rates among patients with different gender, ethnicity, and socioeconomic status within the Kaiser Permanente Mid-Atlantic States (KPMAS) AF population. This retrospective study investigated 9513 patients in KPMAS’s AF registry with CHADS2 score >2 over a 6 month period from March to September 2021. We compared appropriate rates of anticoagulation across subsets of gender, ethnicity, and socioeconomic status by social vulnerability index socioeconomic status (SVI-SES) quartile. Rates were compared using Pearson's Chi-squared tests with SAS Version 9.4. Appropriately anticoagulated patients had higher rates of diabetes, prior stroke, and congestive heart failure than patients who were not appropriately anticoagulated. There were no differences in anticoagulation rates between males and females (71.8% vs. 71.6% [OR] 1.01; 95% CI, 0.93-1.11; P =.76). There was a statistically significant difference between blacks and whites (70.8% vs. 73.1%, P =.03) and Asians and whites (68.3% vs. 71.6%, P=.005). After adjusting for CHADS2 risk factors, this difference persisted for blacks and whites with CHADS2 scores of 2 (62.6% vs. 70.6%, P<.001) and for Asians and whites with CHADS2 scores >5 (68.0% vs. 79.3%, P<.001).There were no differences in anticoagulation rates between SES-SVI quartile. Appropriate anticoagulation rates within KPMAS appear to be higher than what has been reported in National Registry data. There was no difference in appropriate anticoagulation between males and females. Asians and blacks may have a lower rate of appropriate anticoagulation when compared with white patients. Characterizing such disparities is the first step towards addressing treatment gaps in atrial fibrillation.

Abstract 12: Oral Anticoagulant Prescribing For Older Adults Newly Diagnosed With Atrial Fibrillation During Hospitalization

Background: Oral anticoagulants are indicated in patients with atrial fibrillation (AF) at elevated thromboembolic risk. AF is often diagnosed during hospitalization, yet little is known about rates of anticoagulant initiation in this setting. Methods: We examined a 20% national sample of Medicare fee-for-service beneficiaries enrolled in Part D, aged &gt; 65 years, who were hospitalized in 2016, and who received a new diagnosis of AF. The primary outcome was anticoagulant claim within 7 days of discharge home. We used multivariable logistic regression and post-estimation predicted probabilities to identify predictors of discharge with an anticoagulant, hypothesizing that thromboembolic risk, bleeding risk, and frailty would independently influence anticoagulant initiation. Results: Among 31,889 patients diagnosed with AF while hospitalized (mean age, 78; 52% female; 84% white; 95% CHA 2 DS 2 -VASc ≥2; 84% HAS-BLED ≥2; 37% frail), one-quarter initiated an anticoagulant following discharge. In multivariable models, rates of anticoagulant initiation varied by primary reason for hospitalization, with the highest predicted probability of initiation among those with a primary diagnosis of AF (46.3%; 95% CI 45.1-47.5), followed by cardiac surgery (42.8%; 39.6-46.0), other cardiovascular conditions (25.1%; 24.3-26.0), non-cardiac diagnoses (18.6%; 17.3-19.9), and bleeds (3.6%; 2.3-5.0). Higher CHA 2 DS 2 -VASc score was associated with a small increase in anticoagulant initiation (predicted probability 19.8% [15.4-24.2] for CHA 2 DS 2 -VASc &lt;2 and 25.2% [24.7-25.7] for ≥4). Higher HAS-BLED score was associated with a small decrease (25.7% [24.6-26.8] for HAS-BLED &lt;2 and 23.4% [22.7-24.1] for ≥3). Increased frailty was associated with decreased likelihood of anticoagulant initiation, with robust and moderately-severely frail patients having predicted probabilities of 25.0% (23.3-26.6) and 17.6% (15.9-19.2) respectively. Discussion: Anticoagulant initiation is uncommon among older adults newly diagnosed with AF during hospitalization, even among those hospitalized primarily for AF and those with high thromboembolic risk. Providers should carefully weigh risks and benefits of anticoagulants with all inpatients found to have AF.