Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Empagliflozin to prevent post-operative atrial fibrillation in patients undergoing coronary artery bypass graft surgery: Rationale and design of the EMPOAF trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common types of acute AF and can complicate the treatment course of approximately one third of patients undergoing cardiac surgery. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are among the newest antidiabetic drugs which can be therapeutic options for preventing POAF by different mechanisms. METHODS: Empagliflozin to Prevent POAF (EMPOAF) is an interventional, investigator-initiated, double-blind, placebo-controlled, multicenter, randomized controlled trial which will be conducted in two referral teaching cardiology hospitals in Tehran. Four-hundred ninety-two adult patients who are scheduled for elective isolated coronary artery bypass graft (CABG) surgery will be randomly assigned to one of the groups of intervention (empagliflozin 10 mg daily) or placebo starting at least 3 days before surgery until discharge. Key exclusion criteria are a history of diabetes mellitus, AF, ketoacidosis, or recurrent urinary tract infections along with severe renal or hepatic impairment, unstable hemodynamics, and patients receiving SGLT2 inhibitors for another indication. The primary outcome will be the incidence of POAF. Key secondary endpoints will be the composite rate of life-threatening arrhythmias, postoperative acute kidney injury, hospitalization length, in-hospital mortality, stroke, and systemic embolization. Key safety endpoints will be the rate of life-threatening and/or genitourinary tract infections, hypoglycemia, and ketoacidosis. CONCLUSIONS: EMPOAF will prospectively evaluate whether empagliflozin 10 mg daily can reduce the rate of POAF in patients undergoing elective CABG. Enrolment into this study has started by November 2023 and is expected to be ended before the end of 2025.

Comparison of Safety and Biological Efficacy of Anakinra (Kineret) Dispensed in Polycarbonate Plastic versus Borosilicate Glass Syringes: A Patient-Level Analysis of VCUART2 and VCUART3 Clinical Trials.

Anakinra is a recombinant human interleukin-1 receptor antagonist approved for the treatment of inflammatory diseases. Kineret is available as a solution prepared in a borosilicate glass syringe. For implementing a placebo-controlled double-blind randomized clinical trial, anakinra is commonly transferred into plastic syringes. However, there is limited data on anakinra's stability in polycarbonate syringes. We described the results of our previous studies on the use of anakinra in glass (VCUART3) versus plastic syringes (VCUART2) compared with placebo. These studies were conducted in patients with ST-segment elevation myocardial infarction (STEMI), and we assessed the anti-inflammatory effects of anakinra versus placebo by comparing the area under the curve for high-sensitivity cardiac reactive protein (AUC-CRP) levels during the first 14 days of STEMI, its clinical effects on heart failure (HF) hospitalization, cardiovascular death, or new diagnosis of HF as well as adverse events profile between groups. The levels of AUC-CRP were 75 (50-255 mg·day/l) for anakinra in plastic syringes versus 255 (116-592 mg·day/l) in placebo and 60 (24-139 mg·day/l) and 86 (43-123 mg·day/l) for anakinra once and twice daily in glass syringes, respectively, compared with placebo 214 (131-394 mg·day/l). The rate of adverse events was also comparable between groups. There were no differences in the rate of HF hospitalization or cardiovascular death in patients who received anakinra in plastic or glass syringes. Fewer cases of new-onset heart failure occurred in patients receiving anakinra in plastic or glass syringes compared with placebo. Anakinra stored in plastic (polycarbonate) syringes provides comparable biologic and clinical effect to glass (borosilicate) syringes. SIGNIFICANCE STATEMENT: Anakinra (Kineret) 100 mg administered subcutaneously in patients with ST-segment elevation myocardial infarction (STEMI) for a duration of up to 14 days appears to have comparable safety and biological efficacy signals when delivered in prefilled glass or transferred into plastic polycarbonate syringes. This may have important implications for the feasibility of designing clinical trials in STEMI and other clinical conditions.

COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment.

COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.

ACE-Inhibitors in Hypertension: A Historical Perspective and Current Insights.

PURPOSE OF REVIEW: This review describes the discovery and development of ACE inhibitors as antihypertensive agents, compares their efficacy, tolerability, and safety to ARBs, and highlights the contemporary issues surrounding ACE inhibitor use for HTN. RECENT FINDINGS: Angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for the management of hypertension (HTN) and other chronic conditions including heart failure and chronic kidney disease. These agents inhibit ACE, the enzyme that is responsible for converting angiotensin (AT) I to AT II. Inhibiting the synthesis of AT II causes arterial and venous vasodilation, natriuresis, and a decrease in sympathetic activity, resulting in the reduction of blood pressure. ACE inhibitors are first-line therapy in HTN management along with thiazide diuretics, calcium channel blockers, and angiotensin receptor blockers (ARB). Along with inhibiting AT II synthesis, inhibition of ACE causes accumulation of bradykinin, increasing the risk of bradykinin-mediated side effects like angioedema and cough. Since ARBs do not work on ACE in the renin-angiotensin system, the risk of angioedema and cough are lower with ARBs. Recent evidence has also suggested ARBs may have neuroprotective effects compared to other antihypertensives, including ACE inhibitors; however, this warrants further study. Currently, ACE inhibitors and ARBs have an equal class of recommendation for first-line treatment for the management of HTN. Recent evidence has shown ARBs to be just as effective as ACE inhibitors for HTN but with improved tolerability.

Select drug-drug interactions with colchicine and cardiovascular medications: A review.

Several randomized clinical trials have demonstrated the clinical utility of colchicine in the prevention and management of various cardiovascular conditions, including secondary prevention of atherosclerotic cardiovascular disease, acute and chronic pericarditis, and atrial fibrillation. As a result, it is reasonable to anticipate increased use of colchicine within the cardiovascular specialty. However, colchicine is metabolized by cytochrome P450 3A4 (CYP3A4) and a substrate of the efflux transporter, P-glycoprotein (P-gp), creating the potential for clinically significant drug-drug interactions (DDIs). Therefore, when colchicine is administered concomitantly with other cardiovascular agents that inhibit CYP3A4 or P-gp, there is an increased risk of significant DDIs, potentially leading to negative sequelae. This article summarizes the evidence supporting the use of colchicine for cardiovascular disease, describes the mechanisms behind DDIs with select cardiovascular medications, and provides suggestions regarding colchicine dosing and management of DDIs to minimize the risk of poor tolerability and colchicine toxicity.

Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study.

BACKGROUND: Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. METHOD: We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. DISCUSSION: The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. TRIAL REGISTRATION: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.

Steroid Use for Recovery of advanced atrioVentricular block Immediately after VALvular surgery (SURVIVAL): A preliminary randomized clinical trial.

BACKGROUND: Atrioventricular block (AVB) is an important complication following valvular surgery. Several factors including inflammation-mediated injury might trigger AVB. METHODS: Patients with advanced postoperative AVB were randomly assigned to receive either dexamethasone (0.4 mg/kg, maximum 30 mg/day) intravenously for 3 days or conservative care only. Primary endpoint was recovery rate in Day 5 since randomization. Secondary endpoints were recovery rate in Day 7 and Day 10, cumulative AVB time, permanent pacemaker (PPM) implantation rate, length of stay in critical care units, and postoperative major adverse events (MAE). RESULTS: We enrolled 139 subjects (48.9% male) with mean age of 59.9 years randomly allocated to intervention group (n = 69) and control group (n = 70). Dexamethasone led to higher recovery rates at Day 5 (82.6% vs. 62.9%, p = .009) and Day 7 (88.4% vs. 61.4%, p < .0001) respectively. This benefit ceased at Day 10 (83.05% vs. 78.6%, p = .547). Median cumulative AVB time was shorter in dexamethasone group compared with control group (41 h vs. 64 h, p = .044). PPM implantation rates were similar between the dexamethasone and control groups (15.9% vs. 17.1%, respectively, p = .849). Median length of stay in intensive care unit (ICU) (10 days vs. 12 days, p = .03) and MAE (17.4% vs. 25.7%, p = .133) tended to be lower with dexamethasone. CONCLUSION: Dexamethasone may serve as a safe and effective medication to help hasten recovery of advanced AVB after valvular surgery.

Preprocedural Colchicine in Patients With Acute ST-elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Randomized Controlled Trial (PodCAST-PCI).

ABSTRACT: Primary percutaneous coronary intervention (PPCI) is the gold standard of treatment in patients with acute ST-elevation myocardial infarction (STEMI). The no-reflow phenomenon (NRP) is a detrimental consequence of STEMI. Colchicine is an anti-inflammatory drug that may help prevent the NRP and improve patient outcomes. In a randomized, double-blind, placebo-controlled clinical trial, 451 patients with acute STEMI who were candidates for PPCI and eligible for enrollment were randomized into the colchicine group (n = 229) and the control group (n = 222). About 321 patients were eligible to participate; 161 patients were assigned to the colchicine group, whereas 160 patients were assigned to the control group. Colchicine was administered 1 mg before PCI and 0.5 mg daily after the procedure until discharge. NRP, measured by angiographic findings including the thrombolysis in myocardial infarction flow grade and the thrombolysis in myocardial infarction myocardial perfusion grade, was reported as the primary outcome. Secondary end points included ST resolution 90 minutes after the procedure, P-selectin, high-sensitivity C-reactive protein, and troponin levels postprocedurally, predischarge ejection fraction, and major adverse cardiac events (MACE) at 1 month and 1 year after PPCI. NRP rates did not show a significant difference between the 2 groups ( P = 0.98). Moreover, the levels of P-selectin, high-sensitivity C-reactive protein, and troponin were not significantly different. MACE and predischarge ejection fraction were also not significantly different between the groups. In patients with STEMI treated by PPCI, colchicine administered before PPCI was not associated with a significant reduction in the NRP and MACE prevention (trial registration: IRCT20120111008698N23).

The effects of vitamin D supplementation on postoperative atrial fibrillation after coronary artery bypass grafting in patients with vitamin D deficiency.

INTRODUCTION: Postoperative atrial fibrillation (POAF) as a common complication of coronary artery bypass grafting (CABG) surgery is associated with increased mortality and morbidity rates. Vitamin D deficiency increases the prevalence of POAF; however, the effects of vitamin D supplementation on the incidence of POAF have not yet been completely elucidated. METHODS: In this prospective, open-label, randomized clinical trial the level of 25-hydroxy vitamin D (25(OH) D) was measured in patients undergoing CABG surgery. Patients with vitamin D insufficiency (defined as 25(OH) D level < 30 ng/ml) were included and randomly assigned to control group to receive either the general standard of care (Group A) or to study group to receive the general standard of care plus oral vitamin D3 , 600,000 IU 5 days before surgery (Group B). The primary outcome of our study was the occurrence of POAF during the first 5 days after CABG surgery. RESULTS: Totally, 93 patients in group B and 103 patients in group A completed the study. The occurrence of POAF was significantly lower in group B as compared to group A (9.68% vs. 20.39%, p = .038). The length of intensive care unit (ICU) stay and hospital stay were reduced in group B patients (2.21 vs. 3.86 days, p < .001 and 7.40 vs. 9.58 days, p = .022, respectively). CONCLUSION: Our study demonstrated that vitamin D supplementation reduces the incidence of POAF, duration of ICU, and hospital stay following CABG surgery.

Management of ST-segment-elevation myocardial infarction during the coronavirus disease 2019 (COVID-19) outbreak: Iranian"247" National Committee's position paper on primary percutaneous coronary intervention.

World Health Organization has designated coronavirus disease 2019 (COVID-19) as a pandemic. During the past several weeks, a considerable burden has been imposed on the Iranian's healthcare system. The present document reviewed the latest evidence and expert opinion regarding the management of ST-segment-elevation myocardial infarction during the outbreak of COVID-19 and outlines a practical algorithm for it.

Pharmacologic Prevention of Myocardial Ischemia-Reperfusion Injury in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

ABSTRACT: Establishing efficient perfusion into the myocardium is the main purpose in patients with acute coronary syndrome, but the process of reperfusion is not without risk and can damage the myocardium paradoxically. Unfortunately, there is no effective treatment for reperfusion injury, and efforts to find an efficient preventive approach are still ongoing. In the past 3 decades, there have been many successful animal studies on how to prevent reperfusion injury; nonetheless, translation to the clinical setting has almost always proven disappointing. In this article, we review clinical studies on the prevention of reperfusion injury in patients with acute coronary syndrome undergoing primary percutaneous coronary intervention in a pharmacologic-based approach. We categorize all the agents that are evaluated for the prevention of myocardial reperfusion injury based on their mechanisms of action into 5 groups: drugs that can reduce oxidative stress, drugs that can affect cellular metabolism, rheological agents that target microvascular obstruction, anti-inflammatory agents, and agents with mixed mechanisms of action. Then, review all the clinical studies of these agents in the setting of primary percutaneous coronary intervention. Finally, we will discuss the possible reasons for the failure in translation of studies into practice and propose potential solutions to overcome this problem.

COVID-19 and Cardiovascular Diseases.

We herein seek to expound on up-to-the-minute information regarding cardiovascular disease in the era of coronavirus disease 2019 (COVID-19) by highlighting acute myocardial injury caused by COVID-19 and probing into its pathophysiology, clinical signs, diagnostic tests, and treatment modalities. We aim to share the latest research findings vis-à-vis cardiovascular disease patients with confirmed or suspected COVID-19 on the association between hypertension and this infectious disease along with the relevant recommendations; describe the mechanism of coronary artery disease in such patients together with the necessary measures in the setting of non-ST-segment elevation acute coronary syndrome, ST-segment elevation myocardial infarction, and chronic coronary syndrome; discuss tachy- and bradyarrhythmias in the COVID-19 setting alongside their treatments; elucidate coagulopathies, venous thromboembolism, and its prophylactic measures in the context of this infection; set out the cardiopulmonary resuscitation protocol as well as the pertinent safety concerns during the current pandemic; and, finally, explicate drug-drug interactions between COVID-19 and cardiovascular medication in hypertension, acute coronary syndrome, heart failure, venous thromboembolism, and arrhythmias.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19).

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

Comparison of the effect of 80 vs 40 mg atorvastatin in patients with isolated coronary artery bypass graft surgery: A randomized clinical trial.

OBJECTIVES: Atorvastatin can decrease cardiac injury after coronary artery bypass graft (CABG) surgery. We compared the effects of 80 and 40 mg of atorvastatin per day on the levels of cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) after an isolated CABG. METHODS: This randomized single-blind parallel clinical trial enrolled 125 patients (mean age = 60.59 ± 8.37 years) who were candidates for elective isolated CABG at the Tehran Heart Center between May 2017 and December 2017. Patients were randomly allocated into two groups to receive either 80 mg (n = 62) or 40 mg of atorvastatin (n = 63) per day, 5 days before surgery. The levels of cTnT and CK-MB, used as myocardial injury markers, were measured at baseline and then at 8 and 24 hours after CABG. RESULTS: The levels of CK-MB and cTnT at baseline and at 8 and 24 hours following CABG were not significantly different between the two groups. Our repeated measures analysis of variance showed that the levels of CK-MB and cTnT increased significantly over time (P < .001). No significant interaction was observed between time and the atorvastatin dosage on the levels of either CK-MB (P = .159) or cTnT (P = .646). In addition, the between-group effects were not significant for CK-MB (P = .632) and cTnT (P = .126). CONCLUSION: The higher dose of atorvastatin (80 mg) did not exert a more protective effect than the standard dose of atorvastatin (40 mg) after CABG surgery.

Analysis of Gender and Race in Pharmacy Faculty and Administrators.

OBJECTIVE: The objective of this report is to identify and characterize the relative likelihood of women and racially minoritized pharmacy faculty being promoted, advancing within leadership roles, and earning comparable salaries. METHODS: Data from the 2010-2021 American Association of Colleges of Pharmacy Profile of Pharmacy Faculty surveys were analyzed to compare odds ratios for promotion, leadership roles, and salary gaps of pharmacy faculty according to race and gender. Changes in the odds ratios over time were characterized by linear regression and predictions about when and if equality would be achieved according to current trends were calculated. RESULTS: Compared to White male counterparts, faculty identifying as women, Black, Hispanic, or Asian had a significantly lower odds ratio of promotion to associate or full professor. Women and Asian faculty also had a lower likelihood of promotion from assistant to associate or Chief Executive Officer (CEO) dean. No demographics studied were more likely than White men to advance in rank or attain associate or CEO dean leadership positions. Furthermore, negative salary gaps for women emerge after promotion from assistant professor, becoming significant and continuing to widen at the associate (-$20,419) and CEO dean (-$37,495) level. CONCLUSION: Despite attention to matters of diversity, equity, and inclusion, female and racially minoritized faculty continue to experience lower rates of promotion, leadership advancement, and wages compared to White male colleagues. These results have negative consequences for recruiting and retaining talented faculty and students, and compromise the benefits that a diverse faculty is known to provide on student learning outcomes.

A Real-World Analysis of New-Onset Heart Failure After Anterior Wall ST-Elevation Acute Myocardial Infarction in the United States.

The 1-year incidence of heart failure (HF) after anterior wall ST-elevation acute myocardial infarction (STEMI) remains difficult to determine because of inconsistencies in reporting, definitions, and adjudication. The objective of this study was to evaluate the 1-year incidence of HF after anterior wall STEMI in a real-world data set using a variety of potential criteria and composite definitions. In a retrospective cohort study, anonymized patient data was accessed through a federated health research network (TriNetX Limited Liability Company (LLC)) of 56 US healthcare organizations (US Collaborative Network). Patients were identified based on the International Classification of Diseases, Tenth Revision criteria for anterior wall STEMI during the 10-year period from 2013 to 2022 and the absence of prespecified signs or symptoms of HF. Values for 1-year incidence were calculated as 1 minus Kaplan-Meier survival at 12 months after anterior wall STEMI. Univariate Cox proportional hazard ratio was calculated to compare risk associated with potential risk factors. The analysis utilized 5 different types of definition criteria for HF: Diagnosis codes, Signs and symptoms, Laboratory/imaging, Medications, and Composites. A total of 34,395 patients from the US Collaborative Network met eligibility criteria and were included in the analysis. The 1-year incidence of HF varied from 2% to 30% depending upon the definition criteria. Although no single criteria exceeded a 1-year incidence of 20%, a simple composite of HF diagnosis (International Classification of Diseases, Tenth Revision-I50) or use of loop diuretic produced a 1-year incidence 26.1% that was used as the benchmark outcome for evaluation of risk factors. Age ≥65 years, Black race, low-density lipoprotein ≥100 mg/100 ml, elevated hemoglobin A1c (7% to 9% and >9%), and body mass index≥35 kg/m2 were also associated with increased risk of HF. In conclusion, patients with anterior wall STEMI continue to be at high risk for new-onset HF. In the absence of structured, prospective, systematically adjudicated diagnostic criteria, composite definitions are more likely to yield accurate estimates of HF incidence.

Direct oral anticoagulants for treatment of venous thrombosis: illustrated review of appropriate use.

Direct oral anticoagulants (DOACs) have become the preferred option for treatment of venous thromboembolism due to their favorable profile compared with other agents such as vitamin K antagonists or low-molecular-weight heparin. However, findings from randomized controlled trials suggest efficacy and/or safety concerns with DOAC use in some clinical contexts. This illustrated review will summarize indications where DOACs have proven efficacy and safety, situations where they fall short, and situations where uncertainty remains compared with other treatments for venous thromboembolism.

Impact of C-reactive protein levels and role of anakinra in patients with ST-elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). The effectiveness of anakinra according to the degree of systemic inflammation in STEMI has not been addressed. METHODS: We analyzed 139 patients from three Virginia Commonwealth University Anakinra Response Trial randomized clinical trials to assess whether CRP levels predicted HF hospitalization or death in patients with STEMI, and if CRP levels influenced the effects of treatment with anakinra. RESULTS: CRP cut-off levels for prediction of the composite of death or HF hospitalization for CRP at admission, 3 and 14 days were, respectively 6.45 mg/L (100% of sensitivity and 66.1% specificity), 26 mg/L (100% of sensitivity and 78% specificity) and 9.56 mg/L (100% of sensitivity and 80% specificity). More patients with elevated CRP levels died or had a HF hospitalization (5/47 [11%] vs 0/82 [0%], p = 0.004 for CRP at admission; 5/32 [15.6%] vs 0/92 [0%], p < 0.001 for day 3 and 5/26 [19%] vs 0/89 [0%], p < 0.001 for day 14). A greater number of patients treated with anakinra had low CRP levels at 3 and 14 days compared to placebo (Odds Ratio 0.11 [95% IC 0.04-0.28], p < 0.0001 and OR 0.35 [95% CI 0.14-0.86], p = 0.02, respectively). Anakinra significantly prevented death or HF hospitalization in patients with high inflammatory burden (p = 0.04 for admission, p = 0.24 for day 3, and p = 0.05 for day 14). CONCLUSION: Patients with elevated CRP had higher incidence of HF hospitalization or death. Anakinra reduced the number of patients with elevated CRP levels and prevented death or HF hospitalization in patients with elevated CRP levels.