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Abstract: The clinical effect of drug-drug interactions (DDIs) between antiplatelets and antiretroviral therapy (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 HIV (PLWH) 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. Ninety-three 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 whether DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or whether underlying platelet reactivity in PLWH is associated with these events., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: DISCLOSURE OF FUNDING AND CONFLICT OF INTEREST All authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients who had percutaneous coronary intervention within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event. Secondary outcomes included VerifyNow platelet reactivity units (PRUs) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42%-45%), followed by NPO status (26%-28%) and MCS alone (22%-24%). The primary outcome of major adverse cardiovascular event occurred in 1 patient (1.1%). Of 92 patients, 77% had a P2Y12 level collected within 24 hours, and 89% of the cohort was able to achieve the goal P2Y12 PRU of <194. The median P2Y12 value within 24 hours of cangrelor initation was 115 PRU (40-168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients who received a drug-eluting stent in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Intracardiac thrombus (ICT) formation is a common complication of several cardiovascular diseases. Warfarin is recommended for treatment of ICT by guidelines based on observational studies occurring before the advent of nonvitamin K antagonist direct oral anticoagulants (DOACs). We aim to evaluate the current prescribing patterns at our institution and to compare the efficacy and safety profiles of warfarin versus DOACs for ICT. This is a retrospective review of adult patients treated with oral anticoagulation for ICT between May 2013 and December 2019. Our primary end point was complete thrombus resolution. Secondary outcomes included time to resolution of thrombus, treatment failure, and duration of therapy. Safety end points included stroke and systemic embolization (SSE) and bleeding events. A total of 123 patients were included (DOAC n = 61; warfarin n = 62). At baseline, more patients in the DOAC group had anemia [6 (10%) vs. 0 (0%), P = 0.013] and alcohol use disorder [6 (10%) vs. 0 (0%), P = 0.013]. Complete thrombus resolution occurred in 50 (82%) and 46 (74%) patients in the DOAC and warfarin groups, respectively (P = 0.298). There was a shorter time to thrombus resolution in the DOAC group versus the warfarin group {63 days [interquartile range (IQR) 40-138] vs. 123 days [IQR 86-244], P = 0.003}. There were no differences found in SSE or bleeding between the groups [DOAC 11 (19%) vs. warfarin 17 (28%), P = 0.213]. For patients with an ICT, treatment with a DOAC for at least 3 months may be a comparable alternative to warfarin in safety and efficacy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)