Validation of high bleeding risk criteria and definition as proposed by the academic research consortium for high bleeding risk.

AIMS: To validate the set of clinical and biochemical criteria proposed by consensus by the Academic Research Consortium (ARC) for High Bleeding Risk (HBR) for the identification of HBR patients. These criteria were categorized into major and minor, if expected to carry in isolation, respectively, ≥4% and <4% Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding risk within 1-year after percutaneous coronary intervention (PCI). High bleeding risk patients are those meeting at least 1 major or 2 minor criteria. METHODS AND RESULTS: All patients undergoing PCI at Bern University Hospital, between February 2009 and September 2018 were prospectively entered into the Bern PCI Registry (NCT02241291). Age, haemoglobin, platelet count, creatinine, and use of oral anticoagulation were prospectively collected, while the remaining HBR criteria except for planned surgery were retrospectively adjudicated. A total of 16 580 participants with complete ARC-HBR criteria were included. After assigning 1 point to each major and 0.5 point to each minor criterion, we observed for every 0.5 score increase a step-wise augmentation of BARC 3 or 5 bleeding rates at 1 year ranging from 1.90% among patients fulfilling no criterion, through 4.01%, 5.98%, 7.42%, 8.60%, 12.21%, 12.29%, and 17.64%. All major and five out of six minor criteria, conferred in isolation a risk for BARC 3 or 5 bleeding at 1 year exceeding 4% at the upper limit of the 95% confidence intervals. CONCLUSION: All major and the majority of minor ARC-HBR criteria identify in isolation patients at HBR.

Oncologic long-term outcomes of emergency versus elective resection for colorectal cancer.

PURPOSE: Long-term outcomes in patients undergoing emergency versus elective resection for colorectal cancer (CRC) are discussed controversially. This study aims to assess long-term outcomes of emergency versus elective CRC surgery. METHODS: Single-center retrospective cohort study. Patients undergoing emergency or elective CRC surgery from July 2002 to January 2013 were included. Primary outcome was 5-year survival, secondary outcomes were in-hospital mortality and local tumor recurrence. RESULTS: Overall, 475 patients were included. Median age was 69.0 (IQR 59.0-77.0) years. A total of 141 patients (30%) were operated for rectal cancer and 334 patients (70%) for colon cancer. Median follow-up was 445 (IQR 67-1409) days. Emergency resection was performed in 105 patients (22%) due to obstruction, perforation, or bleeding. Stage IV tumors and ASA scores≥ 3 were significantly more frequent in the emergency than in the elective resection group (39.0% vs. 33.5%, p < 0.001; 75.5% vs. 61.3%, p = 0.003). The rate of patients with positive lymph nodes was similar in the two groups (46.2% vs. 46.3%, p = 1.000). In-hospital mortality was significantly higher in the emergency CRC versus the elective CRC group (8.4% vs. 3.0%, p = 0.023). Five-year survival (aHR 1.38; 95%CI 0.81-2.37, p = 0.237) or local tumor recurrence (aHR 1.48; 95%CI 0.47-4.66, p = 0.500) were not significantly different in patients undergoing emergency versus elective surgery for CRC. CONCLUSION: In-hospital mortality was increased in emergency versus elective CRC resections. However, 5-year survival and local recurrence after surgery for CRC were determined by the tumor stage, and not by the emergency versus elective setting of surgical resection.

Electrocardiographic Changes after Endovascular Mechanical Thrombectomy in a Patient with Pulmonary Embolism-A Case Report and Literature Review.

Background: Pulmonary embolism (PE) is a common disease with an annual incidence of about 1/1000 persons. About every sixth patient dies within the first 30 days after diagnosis. The electrocardiogram (ECG) is one of the first diagnostic tests performed, and is able to confirm the suspicion of PE with typical electrocardiographic signs. Some ECG signs and their regression are also prognostically relevant. Endovascular mechanical thrombectomy is one option for PE treatment, and aims to relieve right heart strain immediately. The first studies on endovascular mechanical thrombectomy using a dedicated device (FlowTriever System, Inari Medical, Irvine, CA, USA) yielded promising results. Methods: In the following, we report the case of a 66-year-old male patient who presented with New York Heart Association III dyspnea in our emergency department. Among typical clinical and laboratory results, he displayed very impressive electrocardiographic and radiological findings at the time of PE diagnosis. Results: After endovascular mechanical thrombectomy, the patient's complaints and pulmonary hemodynamics improved remarkably. In contrast, the ECG worsened paradoxically 18 h after intervention. Nevertheless, control echocardiography 4 days after the intervention no longer showed any signs of right heart strain, and dyspnea had disappeared completely. At a 4-month follow-up visit, the patient presented as completely symptom-free with a high quality of life. His ECG and echocardiography were normal and excluded recurrent right heart strain. Conclusions: Overall, the patient benefitted remarkably from endovascular mechanical thrombectomy, resulting in an almost complete resolution of electrocardiographic PE signs at the 4-month follow-up after exhibiting multiple typical electrocardiographic PE signs at time of diagnosis and initial electrocardiographic worsening 18 h post successful intervention.

Acute Coronary Occlusion in Patients With Non-ST-Segment Elevation Out-of-Hospital Cardiac Arrest.

BACKGROUND: According to current guidelines, hemodynamic status should guide the decision between immediate and delayed coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-segment elevation. A delayed strategy is advised in hemodynamically stable patients, and an immediate approach is recommended in unstable patients. OBJECTIVES: This study sought to assess the frequency, predictors, and clinical impact of acute coronary occlusion in hemodynamically stable and unstable OHCA patients without ST-segment elevation. METHODS: Consecutive unconscious OHCA patients without ST-segment elevation who were undergoing CAG at Bern University Hospital (Bern, Switzerland) between 2011 and 2019 were included. Frequency and predictors of acute coronary artery occlusions and their impact on all-cause and cardiovascular mortality at 1 year were assessed. RESULTS: Among the 386 patients, 169 (43.8%) were hemodynamically stable. Acute coronary occlusions were found in 19.5% of stable and 24.0% of unstable OHCA patients (P = 0.407), and the presence of these occlusions was predicted by initial chest pain and shockable rhythm, but not by hemodynamic status. Acute coronary occlusion was associated with an increased risk of cardiovascular death (adjusted HR: 2.74; 95% CI: 1.22-6.15) but not of all-cause death (adjusted HR: 0.72; 95% CI: 0.44-1.18). Hemodynamic instability was not predictive of fatal outcomes. CONCLUSIONS: Acute coronary artery occlusions were found in 1 in 5 OHCA patients without ST-segment elevation. The frequency of these occlusions did not differ between stable and unstable patients, and the occlusions were associated with a higher risk of cardiovascular death. In OHCA patients without ST-segment elevation, chest pain or shockable rhythm rather than hemodynamic status identifies patients with acute coronary occlusion.

Enoxaparin for outpatients with COVID-19: 90-day results from the randomised, open-label, parallel-group, multinational, phase III OVID trial.

INTRODUCTION: The benefits of early thromboprophylaxis in symptomatic COVID-19 outpatients remain unclear. We present the 90-day results from the randomised, open-label, parallel-group, investigator-initiated, multinational OVID phase III trial. METHODS: Outpatients aged 50 years or older with acute symptomatic COVID-19 were randomised to receive enoxaparin 40 mg for 14 days once daily vs. standard of care (no thromboprophylaxis). The primary outcome was the composite of untoward hospitalisation and all-cause death within 30 days from randomisation. Secondary outcomes included arterial and venous major cardiovascular events, as well as the primary outcome within 90 days from randomisation. The study was prematurely terminated based on statistical criteria after the predefined interim analysis of 30-day data, which has been previously published. In the present analysis, we present the final, 90-day data from OVID and we additionally investigate the impact of thromboprophylaxis on the resolution of symptoms. RESULTS: Of the 472 patients included in the intention-to-treat population, 234 were randomised to receive enoxaparin and 238 no thromboprophylaxis. The median age was 57 (Q1-Q3: 53-62) years and 217 (46 %) were women. The 90-day primary outcome occurred in 11 (4.7 %) patients of the enoxaparin arm and in 11 (4.6 %) controls (adjusted relative risk 1.00; 95 % CI: 0.44-2.25): 3 events per group occurred after day 30. The 90-day incidence of cardiovascular events was 0.9 % in the enoxaparin arm vs. 1.7 % in controls (relative risk 0.51; 95 % CI: 0.09-2.75). Individual symptoms improved progressively within 90 days with no difference between groups. At 90 days, 42 (17.9 %) patients in the enoxaparin arm and 40 (16.8 %) controls had persistent respiratory symptoms. CONCLUSIONS: In adult community patients with COVID-19, early thromboprophylaxis with enoxaparin did not improve the course of COVID-19 neither in terms of hospitalisation and death nor considering COVID-19-related symptoms.

Comparative Outcomes After Percutaneous Coronary Intervention in Unconscious and Conscious Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Up to 70% of out-of-hospital cardiac arrest (OHCA) patients have a relevant coronary stenosis which may need revascularization. The short- and long-term ischemic and bleeding risk of unconscious and conscious OHCA patients undergoing percutaneous coronary intervention (PCI) is largely unknown. OBJECTIVES: This study sought to compare the occurrence of 1-year outcomes after PCI between OHCA patients, stratified on the basis of state of consciousness, with patients with acute coronary syndrome (ACS) not preceded by OHCA. METHODS: The study assessed the unadjusted and adjusted risk of cardiovascular events in a prospective single-center cohort of 9,303 consecutive PCI patients. RESULTS: At 1 year, all-cause mortality was higher in unconscious (49.5%) but not in conscious OHCA (8.9%) patients than in ACS patients (8.0%), and both unconscious and conscious OHCA patients were more likely than ACS patients to experience definite stent thrombosis (4.4% and 3.5% vs 1.3%) and Bleeding Academic Research Consortium 3 or 5 bleeding (17.8% and 9.0% vs 5.1%). The higher hazards were largely determined by events occurring in the first 30 days. After multivariable adjustment, only unconscious OHCA patients remained at increased risk of death (adjusted HR: 3.27; 95% CI: 2.65-4.05), definite stent thrombosis (adjusted HR: 2.40; 95% CI: 1.30-4.43), and Bleeding Academic Research Consortium 3 or 5 bleeding (adjusted HR: 2.51; 95% CI: 1.82-3.47) at 1 year. CONCLUSIONS: At 1 year after PCI, unconscious OHCA patients were at higher risk of death, definite stent thrombosis, and bleeding, while conscious OHCA patients had similar hazards compared with an all-comer ACS population without OHCA. Dedicated PCI strategies for OHCA patients taking into account their state of consciousness after resuscitation are warranted.

Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

BACKGROUND: COVID-19 is a viral prothrombotic respiratory infection. Heparins exert antithrombotic and anti-inflammatory effects, and might have antiviral properties. We aimed to investigate whether thromboprophylaxis with enoxaparin would prevent untoward hospitalisation and death in symptomatic, but clinically stable outpatients with COVID-19. METHODS: OVID was a randomised, open-label, parallel-group, investigator-initiated, phase 3 trial and was done at eight centres in Switzerland and Germany. Outpatients aged 50 years or older with acute COVID-19 were eligible if they presented with respiratory symptoms or body temperature higher than 37·5°C. Eligible participants underwent block-stratified randomisation (by age group 50-70 vs >70 years and by study centre) in a 1:1 ratio to receive either subcutaneous enoxaparin 40 mg once daily for 14 days versus standard of care (no thromboprophylaxis). The primary outcome was a composite of any untoward hospitalisation and all-cause death within 30 days of randomisation. Analysis of the efficacy outcomes was done in the intention-to-treat population. The primary safety outcome was major bleeding. The study was registered in ClinicalTrials.gov (NCT04400799) and has been completed. FINDINGS: At the predefined formal interim analysis for efficacy (50% of total study population), the independent Data Safety Monitoring Board recommended early termination of the trial on the basis of predefined statistical criteria having considered the very low probability of showing superiority of thromboprophylaxis with enoxaparin for the primary outcome under the initial study design assumptions. Between Aug 15, 2020, and Jan 14, 2022, from 3319 participants prescreened, 472 were included in the intention-to-treat population and randomly assigned to receive enoxaparin (n=234) or standard of care (n=238). The median age was 57 years (IQR 53-62) and 217 (46%) were women. The 30-day risk of the primary outcome was similar in participants allocated to receive enoxaparin and in controls (8 [3%] of 234 vs 8 [3%] of 238; adjusted relative risk 0·98; 95% CI 0·37-2·56; p=0·96). All hospitalisations were related to COVID-19. No deaths were reported during the study. No major bleeding events were recorded. Eight serious adverse events were recorded in the enoxaparin group versus nine in the control group. INTERPRETATION: These findings suggest thromboprophylaxis with enoxaparin does not reduce early hospitalisations and deaths among outpatients with symptomatic COVID-19. Futility of the treatment under the initial study design assumptions could not be conclusively assessed owing to under-representation of older patients and consequent low event rates. FUNDING: SNSF (National Research Programme COVID-19 NRP78: 198352), University Hospital Zurich, University of Zurich, Dr-Ing Georg Pollert (Berlin), Johanna Dürmüller-Bol Foundation.

Sex-Based Differences in Bleeding Risk After Percutaneous Coronary Intervention and Implications for the Academic Research Consortium High Bleeding Risk Criteria.

Background Female sex was not included among the high bleeding risk (HBR) criteria by the Academic Research Consortium (ARC) as it remains unclear whether it constitutes an HBR condition after percutaneous coronary intervention. We investigated whether female sex associates with HBR and assessed the performance of ARC HBR criteria separately in women and men. Methods and Results Among all consecutive patients undergoing percutaneous coronary intervention between 2009 and 2018, bleeding occurrences up to 1 year were prospectively collected and centrally adjudicated. All but one of the originally defined ARC HBR criteria were assessed, and the ARC HBR score generated accordingly. Among 16 821 patients, 25.6% were women. Compared with men, women were older and had lower creatinine clearance and hemoglobin values. After adjustment, female sex was independently associated with access-site (adjusted hazard ratio, 2.14; 95% CI, 1.22-3.74; P=0.008) but not with overall or non-access-site 1-year Bleeding Academic Research Consortium 3 or 5 bleeding. This association remained consistent when the femoral but not the radial approach was chosen. The ARC HBR score discrimination, using the original criteria, was lower among women than men (c-index 0.644 versus 0.688; P=0.048), whereas a revised ARC HBR score, in which age, creatinine clearance, and hemoglobin were modeled as continuous rather than dichotomized variables, performed similarly in both sexes. Conclusions Female sex is an independent predictor for access-site bleeding but not for overall bleeding events at 1 year after percutaneous coronary intervention. The ARC HBR framework shows an overall good performance in both sexes, yet is lower in women than men, attributable to dichotomization of age, creatinine clearance, and hemoglobin values, which are differently distributed between sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Impact of clinical presentation on bleeding risk after percutaneous coronary intervention and implications for the ARC-HBR definition.

BACKGROUND: The identification of bleeding risk factors in patients undergoing percutaneous coronary intervention (PCI) is essential to inform subsequent management. Whether clinical presentation per se affects bleeding risk after PCI remains unclear. AIMS: We aimed to assess whether clinical presentation per se predisposes to bleeding in patients undergoing PCI and if the Academic Research Consortium (ARC) High Bleeding Risk (HBR) criteria perform consistently in acute (ACS) and chronic (CCS) coronary syndrome patients. METHODS: Consecutive patients undergoing PCI from the Bern PCI Registry were stratified by clinical presentation. Bleeding events at one year were compared in ACS versus CCS patients, and the originally defined ARC-HBR criteria were assessed. RESULTS: Among 16,821 patients, 9,503 (56.5%) presented with ACS. At one year, BARC 3 or 5 bleeding occurred in 4.97% and 3.60% of patients with ACS and CCS, respectively. After adjustment, ACS remained associated with higher BARC 3 or 5 bleeding risk (adjusted HR 1.21, 95% CI: 1.01-1.43; p=0.034), owing to non-access site-related occurrences, which accrued mainly within the first 30 days after PCI. The ARC-HBR score had lower discrimination among ACS compared with CCS patients, and its performance slightly improved when ACS was computed as a minor criterion. CONCLUSIONS: ACS presentation per se predicts one-year major bleeding risk after PCI. The ARC-HBR score discrimination appeared lower in ACS than CCS, and its overall performance improved numerically when ACS was computed as an additional minor risk criterion.