Faculty Bibliography

BACKGROUND/UNASSIGNED:Apixaban is a direct oral anticoagulant (DOAC) that is widely used in the general population; however, its use in solid organ transplant (SOT) recipients has not been extensively studied. Although there is interest in DOACs as the preferred oral anticoagulants in SOT recipients due to their favorable pharmacokinetic properties, there remain concerns for the optimal dose in the setting of organ dysfunction, at the time of engraftment, and for use for off-label indications such as graft thrombosis (GT). OBJECTIVE/UNASSIGNED:To assess "real-world" apixaban utilization in abdominal SOT recipients at a large academic medical center. DESIGN/UNASSIGNED:This was a single-center, observational, retrospective cohort study of 79 adult patients from January 2020 to August 2022 who received apixaban for any indication postabdominal transplant. METHODS/UNASSIGNED:All adult patients, ≥ 18 years of age, who received apixaban for any indication post kidney, liver, simultaneous liver-kidney (SLK), or simultaneous pancreas-kidney (SPK) transplant were included. Electronic health records were retrospectively reviewed for patient demographics, past medical history, and apixaban characteristics, including indication, dose, frequency, and the use of parenteral anticoagulation lead-in for acute thrombosis. The primary outcome was the incidence of thromboembolic events. Secondary outcomes included any bleeding events. In addition, adherence to package label dosing recommendations, based on indication of anticoagulation, was evaluated. RESULTS/UNASSIGNED: = 3), which occurred at a median of 304 (IQR 168-309) days after apixaban initiation. CONCLUSIONS/UNASSIGNED:Apixaban dosing was consistent with labeled dosing for the majority of the cohort for labeled indications, and the observed incidence of thromboembolic events in this cohort was low, with no excess identified relative to published literature. Our data support the use of apixaban for stroke prevention in AF or treatment of VTE or GT in patients who have received an abdominal transplant; however, risk factors for bleeding events, specifically in those with GT, should be further explored.

PURPOSE OF REVIEW/OBJECTIVE:Intraprocedural anticoagulation during percutaneous coronary intervention (PCI) remains particularly challenging in high-risk and underrepresented populations, where the balance between thrombotic and bleeding risk is complex and often unpredictable. This review summarizes contemporary evidence and remaining knowledge gaps regarding anticoagulant selection, dosing, and monitoring in patients with advanced chronic kidney disease (CKD) or end-stage renal disease, cirrhosis, nonagenarians, thrombocytopenia, chronic oral anticoagulation, mechanical circulatory support, and STEMI following fibrinolytic therapy. RECENT FINDINGS/RESULTS:These populations are frequently excluded from randomized clinical trials. In patients with STEMI following fibrinolytic therapy, optimal anticoagulation strategies remain uncertain, with evidence suggesting potential benefit of anticoagulant continuity. Mechanical circulatory support devices introduce additional complexity due to device-related thrombosis and bleeding risks, requiring dynamic, device-specific anticoagulation and monitoring strategies. Special populations such as elderly patients, cirrhosis, and CKD present unique pathophysiologic challenges, including altered pharmacokinetics and rebalanced hemostasis. Similarly, patients on chronic oral anticoagulation require individualized periprocedural strategies, as baseline therapy alone may be insufficient and supplemental intraprocedural anticoagulation is often necessary. Conventional bleeding risk scores demonstrate reduced predictive performance in these populations, highlighting important limitations in current risk stratification. Emerging evidence supports a shift toward precision-guided anticoagulation strategies that integrate actionable patient-specific factors, including renal function, platelet count, liver disease severity, and procedural complexity, along with pharmacogenomics and real-time monitoring. Advances in machine learning-based risk prediction and artificial intelligence-driven clinical decision support tools further offer the potential to enhance individualized care. However, most available evidence remains extrapolated from broader populations, and dedicated prospective studies are needed to define optimal anticoagulant selection, dosing, and monitoring strategies in these high-risk groups.

PURPOSE OF REVIEW/OBJECTIVE:Intraprocedural anticoagulation in the cardiac catheterization laboratory is essential to prevent thrombus formation on catheters, guidewires, and stents while minimizing bleeding risk. This review summarizes contemporary evidence and guideline recommendations for anticoagulation strategies during diagnostic catheterization and percutaneous coronary intervention (PCI). RECENT FINDINGS/RESULTS:Unfractionated heparin (UFH) remains the standard intraprocedural agent, typically administered as a 50-100 U/kg intravenous bolus, and is routinely used during transradial access to prevent radial artery occlusion. Low-molecular-weight heparin (LMWH), particularly enoxaparin, provides more predictable factor Xa-mediated anticoagulation and is an alternative option for patients undergoing PCI in the settings of stable coronary artery disease (CAD), non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI). Bivalirudin, a direct thrombin inhibitor, offers consistent anticoagulation independent of plasma cofactors and, particularly in STEMI, can be combined with a 2-4 h post-PCI infusion to reduce early stent thrombosis. Bivalirudin is an accepted alternative to UFH in both stable CAD and ACS, and is a preferred alternative to UFH to reduce mortality and major bleeding in STEMI (Class I recommendation), as well as in patients with heparin-induced thrombocytopenia or those at high bleeding risk. Fondaparinux has been associated with an increased risk of catheter-related thrombosis and therefore should not be used as a stand-alone intraprocedural anticoagulant during PCI. In PCI, contemporary randomized trials and guideline recommendations support UFH as standard therapy, with enoxaparin and bivalirudin as effective alternatives depending on clinical presentation and bleeding risk. Further studies are needed to refine anticoagulation strategies based on individualized risk factors and procedural context in contemporary PCI.

Precision-based percutaneous coronary intervention (PCI) integrates contemporary strategies across the pre-, intra-, and post-procedural phases to improve outcomes and minimize complications. Emerging evidence underscores the value of these strategies in reducing adverse events and improving procedural efficiency. While artificial intelligence and pharmacogenomics hold long-term promise for enhancing personalization, their clinical utility in PCI remains in the early stages of development.

Therapeutic anticoagulation is the mainstay therapy in acute pulmonary embolism (PE), however, select patients benefit from emergent reperfusion to prevent or rescue acute right ventricular failure and haemodynamic collapse. Compared to other leading causes of cardiovascular mortality such as myocardial infarction and stroke, there is a substantial paucity of literature informing on advanced therapies in PE. Recent years have seen significant evolution in the armamentarium available for PE care with the uptake of several endovascular treatment modalities and increased use of mechanical circulatory support. While several ongoing randomised controlled trials may alter the therapeutic landscape and approach to PE management, at present, we are left with multiple selections with limited guidance. In this review, we discuss the latest therapeutic options available for acute PE and offer an approach to their implementation.

The clinical effect of drug-drug interactions (DDIs) between antiplatelets and antiretrovirals (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with human immunodeficiency virus (PLWH; HIV) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. 93 PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n=84, 71%), followed by ticagrelor (n=9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown if DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or if underlying platelet reactivity in PLWH is associated with these events.

Intravenous (IV) digoxin loading dose recommendations for rate control of atrial arrhythmias in critically ill patients are not well studied. When using digoxin in the setting of atrial fibrillation/atrial flutter (AF/AFL), a loading dose (LD) in either a fixed-dose regimen, weight-based dose, or pharmacokinetic-based calculation to target a serum digoxin concentration (SDC) of 0.8-1.5 ng/mL is recommended. The objective of this study was to assess the safety and effectiveness of digoxin LD used in critically ill patients for rate control of AF/AFL and to assess the SDC achieved. This single center retrospective cohort study included patients who received IV digoxin and had a SDC drawn. The primary endpoint was the median SDC achieved after a digoxin LD. Secondary outcomes included the frequency of SDCs ≥1.5 ng/mL and heart rate (HR) control. A total of 92 patients were included. The median total LD of digoxin for the entire cohort was 11mcg/kg (750 mcg). For 61% of the cohort, the LD was distributed over six-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7). The incidence of supratherapeutic SDC was 36% for the total cohort. A target HR < 110 beats per minute within 24 hours from digoxin LD was achieved in 60% of the cohort. In conclusion, a median total digoxin LD of 750 mcg in critically ill patients with AF/AFL, targeting a SDC < 1.5ng/mL may be considered for acute rate control, taking into account drug-drug interactions in the cardiac intensive care unit. Future studies are necessary to confirm our findings.

INTRODUCTION/BACKGROUND:Data on outcomes between unfractionated heparin and bivalirudin anticoagulation during percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS) remains inconclusive. We aimed to systematically analyze PCI outcomes comparing unfractionated heparin and bivalirudin. METHODS:We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through January 2024 for studies evaluating PCI outcomes comparing unfractionated heparin and bivalirudin. Two investigators independently reviewed data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. RESULTS:Ten prospective trials were identified that enrolled 42,253 individuals who presented with an acute coronary syndrome. Our analysis found that heparin when compared to bivalirudin was associated with an increased risk of trial-based definition of major bleeding (RR 1.68, 95% CI 1.29-2.20), non-access site complications (RR 4.6, 95% CI 1.75-12.09), TIMI major bleeding (RR 1.70, 95% CI 1.20-2.41), major bleeding risks (RR 1.87, 95% CI 1.49-2.36), cardiovascular disease death (RR 1.26, 95% CI 1.02-1.57), and thrombocytopenia (RR 1.67, 95% CI 1.07-2.62). There were no statistically significant differences between heparin and bivalirudin for all-cause mortality, MACE, stroke, reinfarction, target vessel revascularization, acute or stent thrombosis. CONCLUSIONS:The present meta-analysis demonstrates bivalirudin reduces major bleeding when used for anticoagulation during PCI in patients with acute coronary syndromes and is not associated with an increased risk of stent thrombosis or MACE.