Use Of Antiplatelet Medications Research Articles

Antiplatelet Medications and Biomarkers of Hemostasis May Explain the Association of Hematoma Appearance and Subsequent Hematoma Expansion After Intracerebral Hemorrhage.

To test the hypothesis that appearances of intracranial hematomas on diagnostic computed tomography (CT) are not idiosyncratic and reflect a biologically plausible mechanism, we evaluated the association between hematoma appearance on CT, biomarkers of platelet activity, and antiplatelet or anticoagulant medication use prior to admission. We studied 330 consecutively identified patients from 2006 to 2019. Biomarkers of platelet activity (platelet aspirin assay) and medication history (aspirin, clopidogrel) were prospectively recorded on admission. A blinded interpreter recorded the presence of hematoma appearances from the diagnostic scan. Associations were tested with parametric or nonparametric statistics, as appropriate. The black hole sign (101, 30%) was most prevalent, followed by the island sign (57, 17%) and blend sign (32, 10%). There was reduced platelet activity in patients with a black hole sign (511 [430-610] vs. 562 [472-628] aspirin reaction units, P = 0.01) or island sign (505 [434-574] vs. 559 [462-629] aspirin reaction units, P = 0.004). Clopidogrel use prior to admission was associated with the black hole sign (odds ratio 2.25, 95% confidence interval 1.02-4.98, P = 0.04). In patients with acute intracerebral hemorrhage, hematoma appearances on CT are associated with biomarkers of platelet activity and clopidogrel use prior to admission. Appearances of intracranial hematomas on CT may reflect reduced hemostasis from antiplatelet medication use.

Atrial Fibrillation Is Not Associated With Sudden Sensorineural Hearing Loss.

The aim of this study is to assess the association between atrial fibrillation (AF) and sudden sensorineural hearing loss (SSNHL). This study was conducted by searching the longitudinal health insurance database of the Taiwan National Health Insurance Program for relevant information from January 1, 2000, to December 31, 2011. Patients with AF were matched with non-AF controls with a 1:1 strategy according to propensity scores. Multiple logistic regression analyses were performed to determine the risk of SSNHL. In total, 14 698 patients with AF were matched with the same number of non-AF patients as controls. After propensity score matching, the use of antiplatelet or anticoagulation medications and the occurrence of SSNHL were found to have a significant difference between AF and non-AF patients. The occurrence of SSNHL was found to be higher in men, those of 45 to 74 years old, and patients with hypertension in both AF and non-AF groups. Multiple logistic regression analyses revealed that male gender, age between 45 and 74 years, hyperlipidemia, and hypertension are risk factors for SSNHL. The use of aspirin was found to reduce the rate of SSNHL (odds ratio [OR]: 0.67, 95% CI: 0.49-0.94, P = .019), but AF was not found to be a risk factor for SSNHL (OR: 0.89, 95% CI: 0.64-1.23, P = .467). The association between AF and SSNHL is not significant.

Rapid detection of platelet inhibition and dysfunction in traumatic brain injury: A prospective observational study.

Rapid platelet function testing is frequently used to determine platelet function in patients with traumatic intracranial hemorrhage (tICH). Accuracy and clinical significance of decreased platelet response detected by these tests is not well understood. We sought to determine whether VerifyNow and whole blood aggregometry (WBA) can detect poor platelet response and to elucidate its clinical significance for tICH patients. We prospectively enrolled patients with isolated tICH between 2018 and 2020. Demographics, medical history, injury characteristics, and patient outcomes were recorded. Platelet function was determined by VerifyNow and WBA testing at the time of arrival to the trauma bay and 6 hours later. A total of 221 patients were enrolled, including 111 patients on no antiplatelet medication, 78 on aspirin, 6 on clopidogrel, and 26 on aspirin and clopidogrel. In the trauma bay, 29.7% and 67.7% of patients on no antiplatelet medication had poor platelet response on VerifyNow and WBA, respectively. Among patients on aspirin, 72.2% and 82.2% had platelet dysfunction on VerifyNow and WBA. Among patients on clopidogrel, 67.9% and 88.9% had platelet dysfunction on VerifyNow and WBA. Patients with nonresponsive platelets had similar in-hospital mortality (3 [3.0%] vs. 6 [6.3%], p = 0.324), tICH progression (26 [27.1%] vs. 24 [26.1%], p = 0.877), intensive care unit admission rates (34 [34.3%] vs. 38 [40.0%), p = 0.415), and length of stay (3 [interquartile range, 2-8] vs. 3.2 [interquartile range, 2-7], p = 0.818) to those with responsive platelets. Platelet transfusion did not improve platelet response or patient outcomes. Rapid platelet function testing detects a highly prevalent poor platelet response among patients with tICH, irrespective of antiplatelet medication use. VerifyNow correlated fairly with whole blood aggregometry among patients with tICH and platelet responsiveness detectable by these tests did not correlate with clinical outcomes. In addition, our results suggest that platelet transfusion may not improve clinical outcomes in patients with tICH. Diagnostic tests, level II.

EFFECT OF ANTICOAGULATION AND ANTIPLATELET AGENTS ON HYPERCOAGULABILITY STATES IN PATIENTS WITH COVID-19

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: We retrospectively investigated COVID-19 patients on anticoagulation or antiplatelet medications as their home medication or used as inpatient treatment to evaluate if they exhibited lower levels of D-dimer and lower rates of embolic events and mortality. METHODS: This correlational retrospective study evaluated n=319 COVID-19 patients admitted to acute inpatient services across the Mercy Health Youngstown hospitals. A retrospective chart audit included home medications and admission medications, hospital and ICU length of stay, days on the ventilator, initial and follow-up labs (D-dimer), and thromboembolic events after diagnosis of COVID-19. We constructed a composite index for any embolic events occurring in inpatient: MI, DVT, PE, stroke, and cardiac arrest. The prevalence of these embolic events was 23.5% (n=75/319). For propensity modeling, comorbidities, initial D-dimer, demographics, days from a positive COVID-19 test result to admission, and a summative index of comorbidities were entered in a binary logistic regression model to predict embolic events. RESULTS: The rate of any embolic events among COVID inpatients was 23.5% (n=75/319). Initial D-dimer was 1648±1702 ng/mL among patients experiencing any embolic events and was lower among patients without embolic events, 1009±1205 ng/mL (t=3.638, p < 0.001). In iterative forward selection, logistic modeling retained in the model for embolic events were age, initial D-dimer, past medical history of ESRD, and ethnicity, which correctly classified 75% of embolic events in patients (AUC=0.702). The addition of home medications, antiplatelets and anticoagulants to the propensity model did not significantly improve AUC (0.704) which indicates that neither home use of anticoagulation nor antiplatelets was associated with inpatient embolic events in a propensity adjusted model. However, when inpatient anticoagulation therapy was initiated, statistically significant benefit in preventing embolic events was observed (AOR = 3.32 (95% CI 1.79-6.16); AUC 0.752 (p < 0.001)). Similarly, home use of antiplatelet and anticoagulation medications was not associated with mortality in COVID-19 patients, but in-hospital use of anticoagulation was statistically significant (p=0.036). CONCLUSIONS: Our study aimed to see if taking antiplatelet or anticoagulation medications as a home medication would have any effect on thromboembolic events and mortality in COVID-19 patients compared to when receiving antiplatelet or anticoagulation agents during hospitalization. We found that being on an antiplatelet or anticoagulation medication at home (before hospitalization) did not prevent COVID-19 patients from thromboembolic events or improve mortality. However, after adjusting for baseline risk of embolic events, in-hospital anticoagulation had a statistically significant benefit in preventing embolic events and mortality. CLINICAL IMPLICATIONS: It has been established that COVID-19 patients are at higher risk for embolic events that have been linked to increased mortality. In our current study using a composite index model to predict embolic events in COVID-19 patients, the use of anticoagulation agents during hospitalization revealed a significant reduction in embolic risks and mortality while patients on home antiplatelet or anticoagulation medications did not show benefits in reducing the same risks. DISCLOSURES: No relevant relationships by Omotooke Babalola, source=Web Response No relevant relationships by Timothy Barreiro, source=Web Response No relevant relationships by David Gemmel, source=Web Response No relevant relationships by Oyidiya Osoka, source=Web Response No relevant relationships by Jeannie Ur, source=Web Response

Nailfold capillaroscopy and microvascular involvement in Diabetes Mellitus

Objective: to study the relationship between microvascular lesions of Diabetes Mellitus and alterations in the nailfold capillaroscopy. Subjects and Methods: cross-sectional study including 140 individuals (70 with Diabetes Mellitus and 70 controls). Epidemiological and clinical variables were collected from patient’s charts. Fundus ophthalmoscopy, nailfold capillaroscopy, analysis of microalbuminuria and renal clearance as well as fasting glycaemia and HbA1c values were studied simultaneously.Results: capillary density was reduced, and vascular dilatation was increased in Diabetes Mellitus patients when compared to controls (both with p&lt;0.0001). In diabetic individuals the number of dermal papillary capillaries/mm3 correlated negatively with microalbuminuria (p=0.02), patient’s age (p=0.03), values of HbA1c (p=0.03). Patients with diabetic retinopathy and using antiplatelet agents had lower capillary density (p&lt;0.0001 and 0.04 respectively). Capillary dilatation was associated with disease duration (p=0.04).Conclusion: microvascular disease in Diabetes Mellitus is reflected in nailfold capillaroscopy. Decreased capillary density, increased number of ectasias and increased presence of avascular areas were observed in patients with diabetes when compared to controls. In the present study, capillary density correlated/ associate with age, retinopathy, use of antiplatelet medication, HbA1c, microalbuminuria and diabetes duration. Ectasias or dilatations were related to retinopathy, glomerular filtration rate and longer disease duration.

Preprocedural Hypertension Is Not a Risk Factor for Postoperative Bleeding following Image-Guided Core Needle Breast Biopsy.

Objective To evaluate the association between preprocedural hypertension and the risk of prolonged bleeding following image-guided core needle breast biopsy in nonpregnant/nonlactating women. Methods A single institution-based, retrospective cohort study of 400 women who underwent image-guided core needle breast biopsy was conducted. Males and pregnant and lactating women were excluded. Preprocedural systolic or diastolic blood pressure greater than 140 or 90 mm of Hg, respectively, was defined as hypertension. Prolonged bleeding was defined >15 minutes of local, manual pressure required to achieve hemostasis following the biopsy. Severe bleeding complications defined as clinical significant hematoma formation, prolonged bleeding requiring an ER visit, hospitalization, or surgical intervention were also recorded. Results The difference in the mean time for which manual pressure was held after biopsy for patients with and without preprocedural hypertension was not statistically significant (13 ± 7 vs. 13 ± 8 minutes, respectively, P = 0.856). There was no difference in the number of patients requiring manual postoperative pressure >15 minutes between those with preprocedural hypertension and the normotensive patients (13% vs. 12%, respectively, P = 0.765). Bivariate analysis demonstrated statistically significant association between prolonged bleeding and current antithrombotic or antiplatelet medication use (P = 0.010), the use of stereotactic guidance (P = 0.019), and a tethered vacuum-assisted device (P = 0.045). The use of a tethered vacuum-assisted biopsy device was the only variable associated with prolonged bleeding in the multivariate model (P = 0.044). Conclusion Preprocedural hypertension is not a risk factor for prolonged bleeding following image-guided core needle breast biopsies in nonpregnant/nonlactating women.

Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis.

Gut microbiota and their generated metabolites impact the host vascular phenotype. The metaorganismal metabolite trimethylamine N-oxide (TMAO) is both associated with adverse clinical thromboembolic events, and enhances platelet responsiveness in subjects. The impact of TMAO on vascular Tissue Factor (TF) in vivo is unknown. Here, we explore whether TMAO-enhanced thrombosis potential extends beyond TMAO effects on platelets, and is linked to TF. We also further explore the links between gut microbiota and vascular endothelial TF expression in vivo. In initial exploratory clinical studies, we observed that among sequential stable subjects (n = 2989) on anti-platelet therapy undergoing elective diagnostic cardiovascular evaluation at a single-site referral centre, TMAO levels were associated with an increased incident (3 years) risk for major adverse cardiovascular events (MACE) (myocardial infarction, stroke, or death) [4th quartile (Q4) vs. Q1 adjusted hazard ratio (HR) 95% confidence interval (95% CI), 1.73 (1.25-2.38)]. Similar results were observed within subjects on aspirin mono-therapy during follow-up [adjusted HR (95% CI) 1.75 (1.25-2.44), n = 2793]. Leveraging access to a second higher risk cohort with previously reported TMAO data and monitoring of anti-platelet medication use, we also observed a strong association between TMAO and incident (1 year) MACE risk in the multi-site Swiss Acute Coronary Syndromes Cohort, focusing on the subset (n = 1469) on chronic dual anti-platelet therapy during follow-up [adjusted HR (95% CI) 1.70 (1.08-2.69)]. These collective clinical data suggest that the thrombosis-associated effects of TMAO may be mediated by cells/factors that are not inhibited by anti-platelet therapy. To test this, we first observed in human microvascular endothelial cells that TMAO dose-dependently induced expression of TF and vascular cell adhesion molecule (VCAM)1. In mouse studies, we observed that TMAO-enhanced aortic TF and VCAM1 mRNA and protein expression, which upon immunolocalization studies, was shown to co-localize with vascular endothelial cells. Finally, in arterial injury mouse models, TMAO-dependent enhancement of in vivo TF expression and thrombogenicity were abrogated by either a TF-inhibitory antibody or a mechanism-based microbial choline TMA-lyase inhibitor (fluoromethylcholine). Endothelial TF contributes to TMAO-related arterial thrombosis potential, and can be specifically blocked by targeted non-lethal inhibition of gut microbial choline TMA-lyase.

Incidence of Atrial Fibrillation and Bleeding in CLL Patients Treated with Ibrutinib: Evidence from the Veterans Health Administration

Background: Chronic Lymphocytic Leukemia (CLL) is the second most common type of leukemia in adults, with an estimated 62,130 new cases expected to be diagnosed in 2017 (Siegel, Miller, and Jemal 2017). The introduction of novel oral agents in CLL, starting with ibrutinib (IB) in 2013, has revolutionized the therapeutic landscape, with efficacy and safety that compare favorably overall with prior mainstays of treatment such as chemoimmunotherapy. However, novel agents are associated with specific toxicities that may limit their utility. Several clinical trials have suggested that there is an association between IB and the risk of bleeding-related adverse events and atrial fibrillation (Afib) in CLL patients (Leong et al. 2016; McMullen et al. 2014; Lipsky et al. 2015). The risk of bleeding and Afib in CLL patients treated with IB in a real-world clinical setting is unknown.Aims: This study examines the real-world incidence of bleeding and Afib in CLL patients receiving IBR in the Veterans Health Administration (VHA). We also report the utilization of anticoagulant and antiplatelet medications following treatment with IB. For comparison, the incidence of bleeding and Afib and use of anticoagulant and antiplatelet medications during treatment in a cohort of CLL patients treated with bendamustine and rituximab (BR) is also reported.Methods: Patients who were diagnosed and treated for CLL at the VHA from 2010-2014 were identified through the VA Clinical Cancer Registry (VACCR). Patients were excluded if they had a prior malignancy. Patients were followed until the end of study observation period, death, or lack of utilization of hematology/oncology services for 18 months, or incidence of another cancer. For the IB cohort, patients were indexed at the time of the first dispensation of IB. Comorbidities and medications that could influence incidence of bleeding or Afib were extracted in the six months prior to the index date while the incidence of bleeding and Afib was extracted in the six months following the index date. Charlson Comorbidity Index (CCI),(Deyo 1992; D'Hoore, Bouckaert, and Tilquin 1996) liver disease (cirrhosis, alcoholic liver disease, HCV infection)(Kramer et al., n.d.), and diabetes (controlled and uncontrolled) were examined (Guzman et al. 2014). Treatments dispensed, evidence of VHA system use, bleeding events, and Afib were determined from the administrative records, lab records, pharmacy dispensation records, and clinical notes in the electronic medical record. Descriptive statistics were used to report estimates.Results: From 2010-2014, 2,796 patients were diagnosed and received care for their CLL within the VHA. We identified 172 patients receiving IB and 291 patients receiving BR (table 1).Of the BR patients, 282 (97%) were male. Similarly, 167 (97%) of IB patients were male. The median age at diagnosis was 67 years for BR patients and 69 years for IB patients. The CCI, liver disease and end-stage liver disease comorbidities were higher in patients receiving BR than IB, however, there were significantly more patients with diabetes (both controlled and uncontrolled) who received IB (24%) compared to those who received BR (8%). The use of anticoagulants following induction therapy did not differ between BR and IB patients (9% v 8%), nor did the use of antiplatelets (6% v 2%). Incidence of anticoagulants and antiplatelet usage prior to BR or IB induction therapy was minimal (fewer than 10 patients) and is therefore not reported. Of the 291 patients that received BR, 12 (4%) developed a bleeding event compared to 20 (12%) of the 172 patients that received IB. Additionally, 13 (8%) of IB patients developed Afib compared to only 3% of BR patients.Conclusions: Real-world evidence from a nationwide cohort of CLL patients suggest that while IB is associated with increased bleeding-related adverse events and Afib it is comparable to those reported in previous clinical trials (Leong et al. 2016; Lipsky et al. 2015). Additionally, these findings suggest that patients in real-world clinical care settings with higher levels of comorbidities may be at an increased risk for bleeding events and Afib. [Display omitted] DisclosuresHalwani:Kyowa Hikko Kirin: Research Funding; Bristol Myers Squib: Research Funding; Seattle Genetics: Research Funding; Roche/Genentech Inc.: Research Funding; Genetech Inc.: Research Funding; Takeda: Research Funding; Pharmacyclics: Research Funding; Amgen: Research Funding; AbbVie: Research Funding; Immune Design: Research Funding; Miragen: Research Funding. Sauer:AbbVie: Research Funding; Genentech Inc.: Research Funding; Pharmacyclics: Research Funding; Amgen: Research Funding.

Survey and Analysis of Age and Antiplatelet/Anticoagulation Medication Status of the Desert Regional Medical Center Emergency Department Patients.

ObjectiveTo delineate whether the geographical region served by the Desert Regional Medical Center (DRMC) emergency department (ED) in Palm Springs, California has a higher percentage of patients taking antiplatelet and/or anticoagulant medications during the winter season due to the seasonal influx of elderly patients.MethodWe conducted a prospective study in the patients seen in the DRMC ED between November 12, 2019 and November 14, 2019, and those patients were anonymously surveyed regarding their outpatient use of antiplatelet and anticoagulant medications. Verbal consent for participation was obtained. All the registered patients at the DRMC ED during the prescribed period of time were included. While the patients who were sent home by a triage nurse for non-medical issues or minor ailments requiring no treatment from ED providers and patients who refused to participate or were unable to consent were excluded. Age, gender, medication status including whether on any medication, antiplatelet and anticoagulant use, including dosage, and last dose time were recorded.ResultsOf the 110 consecutive patients arriving to the ED during the study period, 11 patients were unwilling or unable to provide consent for participation. Of the 99 participating patients, 37 (37%) were over 65 years old. The most common antiplatelet and/or anticoagulant medication taken by the patients was aspirin (24 patients). Aspirin was most commonly taken as once a day, in a total of 11 patients (11%). Thirty patients were taking one or more antiplatelet or anticoagulant medications. ConclusionED at a hospital in Palm Springs, California has more elderly visits as compared to the national and California state averages. However, antiplatelet usage in elderly patients in our study was lower than the national average.

Pre-hospital antiplatelet medication use on COVID-19 disease severity

ObjectiveTo evaluate the association between pre-hospitalization antiplatelet medication use and COVID-19 disease severity. DesignRetrospective cohort study. SettingInpatient units at The Mount Sinai Hospital. PatientsAdults age ≥18 admitted between March 1, 2020 and April 9, 2020 with confirmed COVID-19 infection with at least 28 days follow-up. MeasurementsWe captured baseline demographic, pre-hospitalization antiplatelet medication use, and clinical encounter data for all patients who met inclusion criteria. The primary endpoint was peak score on a 6-point modified ordinal scale (MOS), which is based on World Health Organization blueprint R&S groups, used to grade severity of illness through clinical outcomes of interest. Scores indicate the following: 1 – COVID-19 infection not requiring hospitalization, 2 – requiring hospitalization but not supplemental oxygen, 3 – hospitalization requiring supplemental oxygen, 4 – hospitalization requiring high-flow nasal cannula (HFNC) or non-invasive positive pressure ventilation (NIPPV), 5 – hospitalization requiring intubation or extracorporeal membrane oxygenation (ECMO), 6 – death. Multivariable adjusted partial proportional odds model (PPOM) was performed to examine the association between pre-hospitalization antiplatelet medication use and likelihood of each MOS score. Main ResultsOf 762 people admitted with COVID-19, 239 (31.4%) used antiplatelet medications pre-hospitalization while 523 (68.6%) did not. Antiplatelet users were older and had more co-morbidities at baseline. Before adjusting for covariates, patients who used antiplatelet medications pre-hospitalization were more likely than non-users to have peak MOS score 6 (death, OR 1.75, 95% CI 1.21–2.52), peak MOS score ≥5 (intubation/ECMO or death, OR 1.4, 95% CI 1.00–1.98) and peak MOS score ≥4 (HFNC, NIPPV, intubation/ECMO or death, OR 1.40, 95% CI 1.01–1.94). On multivariable adjusted PPOM analysis controlling for 13 covariates, there were no longer any significant differences in peak MOS scores between users and non-users. ConclusionsAfter adjusting for covariates, pre-hospital antiplatelet use was not associated with COVID-19 severity in hospitalized patients.

Intraoperative hematoma volume can predict chronic subdural hematoma recurrence.

Background: We routinely measured the exact chronic subdural hematoma (CSDH) volume during single burr hole surgery. To date, several risk factors have been reported for CSDH recurrence, including sex, hematoma volume and degree of midline shift calculated from computed tomography, use of anticoagulants or antiplatelet medications, and alcohol consumption habits. The aim of this study was to clarify whether hematoma volume, in conjunction with other factors, can predict recurrence.Methods: We retrospectively reviewed the clinical data of 194 consecutive patients with CSDH who underwent single burr hole surgery. The risk factors for recurrence were analyzed based on patients’ sex, age, bilaterality, existence of apparent trauma history, exact intraoperative hematoma volume, and various clinical factors, including preoperative anticoagulant/antiplatelet intake.Results: Recurrence occurred in 22 patients (11.3%). Multivariate logistic regression analysis revealed that intraoperative hematoma volume was an independent risk factor for CSDH recurrence (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.01–1.02, P < 0.001), in addition to sex (male) (OR 9.25; 95% CI, 1.00–84.8; P = 0.049) and diabetes mellitus (DM) (OR: 3.97, 95% CI, 1.34–11.7, P = 0.013). Based on receiver operating characteristics analysis, the cutoff value of the hematoma volume predicting CSDH recurrence was 150 ml (sensitivity and specificity of 72.7% and 72.1%, respectively; area under the curve: 0.7664, 95% CI: 0.654–0.879, P < 0.001). Of these, a hematoma volume ≥150 mL was the strongest independent risk factor for recurrence according to multiple regression (OR: 8.98, 95% CI: 2.73–29.6, P < 0.001) and Cox regression analysis (hazard ratio: 3.05, 95% CI: 1.18–7.87, log-rank P = 0.0046, P = 0.021). Follow-up periods after surgery were significantly longer for cases with recurrence than for non-recurrence cases (24.8 ± 11.5 vs. 15.9 ± 9.7 days), and the recurrence prediction cutoff value was 17 days, with a sensitivity and specificity of 83.1% and 68.2%, respectively (AUC: 0.7707, 95% CI: 0.6695–0.8720, P < 0.001).Conclusion: Intraoperative hematoma volume could be a predictive value for CSDH recurrence.

Reliability of patient‐reported outcome measures: Hemorrhage, anticoagulant, antiplatelet medication use

BackgroundMost antithrombotic medication users are older adults. Patient‐reported outcome measures are commonly used in clinical research on antithrombotic medication, such as the diagnosis of intracranial hemorrhage. ObjectivesTo determine the reliability of patient‐reported intracranial hemorrhage, anticoagulant and platelet aggregation inhibitor use in the older adult population. Patients/MethodsWe conducted a secondary analysis of a prospective, observational cohort study of older adults who presented to the emergency department with a fall. The primary outcome was diagnosis of intracranial bleeding. We compared patient‐reported intracranial bleeding to structured chart review with adjudication. We also compared patient‐reported use of antiplatelet and anticoagulant medication to physician‐reported medication use supplemented with structured chart review. We calculated the diagnostic accuracy of the patient‐reported outcomes using our comparators as the reference standard. ResultsExact agreement for patient‐reported intracranial bleeds was 95%, with a Cohen’s kappa of 0.30 (95% confidence interval [CI], 0.15‐0.45). The sensitivity was 36.7% (95% CI, 20.6%‐56.1%) and specificity 97.2% (95% CI, 95.8%‐98.1%). For anticoagulant medication use, exact agreement was 87%, Cohen’s kappa 0.66 (95% CI, 0.63‐0.72), sensitivity 84.0% (95% CI, 79.3%‐83.8%), and specificity 87.6% (95% CI, 85.1%‐89.7%). For antiplatelet medication use, exact agreement was 77%, Cohen’s kappa 0.50 (95% CI, 0.44‐0.55), sensitivity 68.7% (95% CI, 64.0%‐73.1%), and specificity 81.2% (95% CI, 78.0‐83.8%). ConclusionsPatient‐reported outcome and exposure data were unreliable in this study. Our findings have a bearing on future research study design.

Risk Factors for Severe Bleeding Complications in Vitreoretinal Surgery and the Role of Antiplatelet or Anticoagulant Agents

To evaluate the influences and risk factors for severe bleeding complications during vitreoretinal surgery and to investigate the role of antiplatelet and anticoagulant agents. Prospective trial. Patients undergoing vitreoretinal surgery. The procedures included were pars plana vitrectomy and scleral buckling. We developed a uniform classification to grade the bleeding severity. Bleeding was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and 1 day later, the incidence and the severity of bleeding events was documented on a standardized form. A grade of 3 or more was defined as severe bleeding. Furthermore, the influence of known systemic disorders before surgery, the type of anesthesia, type of surgical procedure, intraoperative blood pressure, and the use or change of antiplatelet or anticoagulant agents on intraoperative bleeding was analyzed. Incidence and risk factors for severe intraoperative bleeding events. Data from 374 eyes undergoing vitreoretinal procedures were included in our study (mean age, 67.6± 12.9 years). A severe intraoperative bleeding event was observed in 15 eyes (4%). We found that concomitant diseases such as diabetes mellitus and carotid artery stenosis, the presence of diabetic retinopathy, younger age, and scleral buckling combined with a transscleral puncture were associated significantly with severe bleeding events. By contrast, use of antiplatelet or anticoagulant agents, or both, had no significant influence on severe intraoperative bleeding events. Although external manipulations during buckling surgery (e.g., drainage of subretinal fluid) and concomitant diseases such as diabetes mellitus and carotid artery stenosis influences the risk of severe intraoperative bleeding events, we did not detect an increased risk related to coexisting antiplatelet or anticoagulant medication use, or both.

Association of Statins With Functional Outcome and 30-Day Mortality in Patients With Intracerebral Hemorrhage.

AimThe effect of statins is well established in cardiac and cerebrovascular diseases. However, its impact on intracerebral hemorrhage (ICH) is unclear. We aim to identify an association of pre-ICH statin treatment and statin use during admission for ICH with functional outcome at discharge and 30-day mortality.Material and methodsA retrospective cohort study was held in patients with ICH admitted to our stroke unit over a year period. Demographic characteristics, risk factors and cardiovascular diseases, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Score (NIHSS), systolic blood pressure (SBP) at admission, cholesterol levels and radiologic findings were analyzed to explore the association between pre-ICH and inpatient statin use with outcomes. The primary endpoint was functional outcome defined as modified Rankin Score (mRS) at discharge and 30-day mortality. We performed a univariate analysis and the variables with statistical significance were included in a multivariate analysis to control for confounding covariates.ResultsThe study included 78 patients, 33 (42.31%) had previous statin intake history, of which 13 (39.39%) maintained statin intake during hospitalization. Regarding functional outcome we did not report a statistically significant difference between groups. In the “pre-ICH statin use” group a decreased 30-day mortality (6.06%, p = 0.009) was observed. In this group it was also noted higher antiplatelet medication use (33.33%, p = 0.006), higher GCS at admission (13-15: 84.38%, p = 0.018) and deep ICH (81.82%, p = 0.030). However, 30-day mortality had no impact in multivariate regression (Odds ratio (OR) 4.535, 95% Confidence Interval (CI) = 0.786-26.173, p = 0.091). In the group that maintained statin treatment during hospitalization no deaths were registered (p = 0.020) and there was no association with functional status. Multivariate regression analysis was not performed due to sample size.ConclusionThe only association demonstrated in this study was lower 30-day mortality with pre-ICH statin use and continued statin treatment during admission. However, this was not confirmed by multivariate regression analysis. There were no differences between groups concerning cholesterol values, results that can be explained by the pleiotropic and immunomodulatory effect of statins. However, prospective studies are needed to prove the benefit of the statins in ICH.

Antiplatelet Therapy after Intracerebral Hemorrhage and Subsequent Clinical Events: A 12-Year South Korean Cohort Study

Introduction: Antiplatelet agents are usually discontinued to reduce hemorrhagic tendency during the acute phase of intracerebral hemorrhage (ICH). However, their use after ICH remains controversial. Methods: This study investigated the effect of antiplatelet agents in ICH survivors. We used the National Health Insurance Service-National Sample Cohort 2002–2013 database for retrospective cohort modeling, estimating the effects of antiplatelet therapy on clinical events. Subgroup analyses assessed antiplatelet medication administered before ICH. Results: The prescription rate of antiplatelets after ICH was also examined. Of 1,007 ICH-surviving patients, 303 subsequent clinical events were recorded, 41 recurrences of nonfatal ICH recurrence, 26 incidents of nonfatal ischemic stroke, 6 nonfatal myocardial infarctions, and 230 incidents of all-cause mortality. The use of antiplatelet therapy significantly decreased the risk of primary outcomes (adjusted hazard ratio [AHR] = 0.743, 95% confidence interval [CI] = 0.578–0.956) and all-cause mortality (AHR = 0.740, 95% CI = 0.552–0.991), especially in patients without a history of antiplatelet treatment. The use of antiplatelet medication after ICH did not significantly increase the recurrence of ICH. The prescription rate of antiplatelet therapy within 1 year was 16.6%. Among 220 patients with a history of using antiplatelet medication, the resumption rate was 0.5% at discharge, 5% after a month, 12.7% after 3 months, and 29.1% after a year. Conclusion: Using antiplatelet treatment after ICH does not increase chances of recurrence, but lowers the occurrence of subsequent clinical events, especially mortality. However, the prescription and resumption rate of antiplatelet therapy after ICH remains low in South Korea.

PLASMA ACE2 ACTIVITY IS INCREASED IN PATIENTS RECOVERED FROM SARS-COV-2 INFECTION: IMPLICATIONS FOR THE PROLONGED CONSEQUENCES OF COVID-19

Objective: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), utilises the catalytic site of membrane-bound angiotensin converting enzyme 2 (ACE2) for cell entry. It is thought that endocytosis of ACE2 results in a decrease in membrane bound ACE2 expression, and disruption of the local tissue renin angiotensin system protection. In this study, we hypothesised that SARS-CoV-2 infection would be associated with shedding of ACE2 leading to increased plasma ACE2 activity. Design and method: Australians aged &gt; 18 years (n = 66) who had recovered from SARS-CoV-2 infection (positive result by PCR testing) and uninfected controls (n = 70) were recruited. Serial samples were available in 23 recovered SARS-CoV-2 patients. Plasma ACE2 activity was measured using a fluorescent substrate-based assay and levels were compared using the Mann-Whitney or Kruskal–Wallis test. Serial ACE2 activity were analysed using the Friedman test for repeated measures. Post-hoc analysis was performed with a Bonferroni correction. Two-tailed P-values &lt; 0.05 were considered significant. Results: Controls and SARS-CoV-2 recovered patients were matched for age (mean ± SD, 54 ± 11 vs. 53 ± 14 years, p = 0.47) and gender (53% vs. 59% male, p = 0.49). There were no significant differences (p &gt; 0.05) in the proportion of hypertension, obesity, diabetes, cardiovascular disease, or use of anti hypertensive, lipid lowering, and anti-platelet medications between the controls and SARS-CoV-2 patients. Plasma ACE2 activity at median 35 days post-infection [interquartile range 30–38 days] was 97-fold higher in SARS-CoV-2 patients compared to controls (5.8 [2–11.3] vs. 0.06 [0.02–2.2] pmol/min/ml, p &lt; 0.0001). Plasma ACE2 activity was significantly different across disease severity (p = 0.033), with severe COVID-19 associated with higher ACE2 activity compared to mild disease (11.2 [8.3–23.2] vs. 5.4 [1.8–9.0] pmol/min/ml, p = 0.027). Men recovered from SARS-CoV-2 had higher ACE2 levels compared to women (9.2 [5.8–15.3] vs. 2.1 [0.2–5.1] pmol/min/ml, p &lt; 0.0001). In 23 patients who had serial blood samples at 63 [56–65] and 114 [111–125] days post infection, median ACE2 activity remained persistently elevated with no differences between time-points (p &gt; 0.05). Conclusions: Plasma ACE2 activity is elevated after SARS-CoV-2 infection and remains elevated post-infection. Our findings indicate the need for ongoing investigation to determine if ACE2 levels identify people at risk of prolonged illness following COVID-19.

Safety of gastrointestinal endoscopy in patients with acute coronary syndrome and concomitant gastrointestinal bleeding.

BACKGROUNDGastrointestinal bleeding (GIB) is a major concern in patients hospitalized with acute coronary syndrome (ACS) due to the common use of both antiplatelet medications and anticoagulants. Studies evaluating the safety of gastrointestinal endoscopy (GIE) in ACS patients with GIB are limited by their relatively small size, and the focus has generally been on upper GIB and esophago-gastroduod-enoscopy (EGD) only. AIMTo evaluate the safety profile and the hospitalization outcomes of undergoing GIE in patients with ACS and concomitant GIB using the national database for hospitalized patients in the United States.METHODSThe Nationwide Inpatient Sample database was queried to identify patients hospitalized with ACS and GIB during the same admission between 2005 and 2014. The International Classification of Diseases Code, 9th Revision Clinical Modification was utilized for patient identification. Patients were further classified into two groups based on undergoing endoscopic procedures (EGD, small intestinal endoscopy, colonoscopy, or flexible sigmoidoscopy). Both groups were compared regarding demographic information, outcomes, and comorbi-dities. Multivariate analysis was conducted to identify factors associated with mortality and prolonged length of stay. Chi-square test was used to compare categorical variables, while Student’s t-test was used to compare continuous variables. All analyses were performed using SAS 9.4 (Cary, NC, United States).RESULTSA total of 35612318 patients with ACS were identified between January 2005 and December 2014. 269483 (0.75%) of the patients diagnosed with ACS developed concomitant GIB during the same admission. At least one endoscopic procedure was performed in 68% of the patients admitted with both ACS and GIB. Patients who underwent GIE during the index hospitalization with ACS and GIB had lower mortality (3.8%) compared to the group not undergoing endoscopy (8.6 %, P < 0.001). A shorter length of stay (LOS) was observed in patients who underwent GIE (mean 6.59 ± 7.81 d) compared to the group not undergoing endoscopy (mean 7.84 ± 9.73 d, P < 0.001). Multivariate analysis showed that performing GIE was associated with lower mortality (odds ratio: 0.58, P < 0.001) and shorter LOS (-0.36 factor, P < 0.001).CONCLUSIONPerforming GIE during the index hospitalization of patients with ACS and GIB was correlated with a better mortality rate and a shorter LOS. Approximately two-thirds of patients with both ACS and GIB undergo GIE during the same hospitalization.

Pre-injury use of antiplatelet and anticoagulations therapy are associated with increased mortality in a cohort of 1038 hip fracture patients.

Hip fractures are a large burden on the health care systems of developed nations. Patients usually have multiple co-morbidities and the pre-injury use of anticoagulants and anti-platelet medication is common. This study used a single hospital hip fracture database to facilitate a retrospective analysis of the impact of anti-coagulation and anti-platelet therapy on mortality and complications after surgical management of hip fractures. There were 92 patients on warfarin, 69 on DOAC, 260 antiplatelet patients and 617 control patients. Mortality rates at 30 days were 4.8% for the control group, 12.6% for the antiplatelet group, warfarin 7.0%, 9.5% for Direct Oral Anticoagulant (DOAC) group, p=0.004. Mortality rates at 1 year were 22.4% for the control group, 32.3% for the antiplatelet group, 29.3% for the warfarin group and 29.0% for DOAC group (p=0.007). Amongst complications, significant differences were found in transfusion (DOAC) and wound ooze (warfarin) rates, but the study did not detect significant clinical consequences arising from these differences. A matched analysis for age, sex, and ASA was undertaken to look in more detail at mortality data. Some mortality differences remained between groups with anti-platelet medication associated with increased mortality, but the differences no longer appeared to be significant. Our data suggests that this is a non-causal association, which could be incorporated into predictive mortality risk scores such as the Nottingham hip fracture score. We believe that pre-injury antiplatelet therapy is a strong indicator for high risk patients with higher expected mortality after hip fracture surgery. We saw no evidence to support delayed surgery in patients taking DOACs.

Systemic antiplatelet agents and anticoagulants in eyes with branch retinal vein occlusion

Purpose:The purpose of this study was to investigate the effect of systemic antiplatelet agents and anticoagulants on the structural and functional outcomes of eyes with branch retinal vein occlusion (BRVO).Methods:A retrospective longitudinal cohort study was performed on BRVO patients evaluated at a single tertiary care referral center between 2009 and 2017. Medical records were reviewed for antiplatelet agent and anticoagulant use including aspirin, clopidogrel, warfarin, rivaroxaban, apixaban, or dabigatran prior to BRVO onset. In addition, optical coherence tomography (OCT) parameters, clinical outcomes, and treatment patterns were also recorded.Results:A total of 354 BRVO eyes were identified with a mean follow-up time of 36 months. Antiplatelet or anticoagulant use was associated with presence of cystoid macular edema (CME) at presentation after controlling for potential confounding variables in a multivariate logistic regression. Multivariate regression also revealed an association between foveal hemorrhage at presentation and use of antiplatelet or anticoagulant medications. There were no significant differences in visual acuity or prevalence of CME at the final visit in those with antiplatelet/anticoagulant use compared to those not on these agents.Conclusion:Although the use of systemic antiplatelet or anticoagulant agents was associated with increased prevalence of CME and foveal hemorrhage at presentation of BRVO, the use of these medications was not associated with different visual or structural outcomes at the final visit.

791. Evaluation of NSAID Exposure as a Risk Factor for Clostridium difficile infection: A Propensity-Score-Matched Case-Control Study

BackgroundExposure to certain medications, particularly antibiotics and proton pump inhibitors, has been associated with increased risk for Clostridium difficile infection (CDI). Studies have suggested an increased risk for CDI associated with exposure to certain non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a retrospective case-control study to evaluate the risk for CDI associated with NSAID use.MethodsThe population included 1338 patients tested for CDI from February–December 2016 at the University of Michigan. NSAID use within 30 days of CDI testing was determined by chart review. Both scheduled and as-needed NSAID use met the definition for exposure, but aspirin use alone did not. Additional clinical data such as comorbid disease and baseline laboratory parameters were extracted through electronic query. A random forest model imputed missing data. A propensity score for NSAID use was developed via logistic regression and included gender, back pain, baseline serum creatinine, osteoarthritis, rheumatoid arthritis, serum albumin, and use of anticoagulant or antiplatelet medications. Cases were matched 1:1 with C. difficile negative controls by propensity score, with a matching caliper of 0.2 x standard deviation of the logit of the score. The final study population consisted of 1256 cases and their matched controls, however 6 cases could not be matched to controls as none had scores within the matching caliper. Conditional logistic regression was used to compare cases to controls.ResultsNSAID use was similar between the two groups on unadjusted analyses. The adjusted, multivariable model demonstrates that non-aspirin NSAID use is not a significant risk factor for CDI (P =.816), after adjustment for comorbid disease burden, age, and history of prior CDI (Table). Older age and prior CDI were independent risk factors for CDI (Table). Table Study population and modeling results ConclusionIn this retrospective case-control study, non-aspirin NSAID use was not associated with an increased risk of CDI. To our knowledge, this is the first study of NSAID use as a risk factor for CDI that accounted for bias due to treatment assignment using a propensity score. Future studies should account for frequency or chronicity of NSAID use, which may affect the results.DisclosuresKrishna Rao, MD, MS, Bio-K+ International, Inc. (Consultant)Merck and Co., Inc. (Research Grant or Support)Roche Molecular Systems, Inc. (Consultant)