Objective: Current guidelines recommend dual antiplatelet (AP) therapy (DAPT) before carotid artery stenting (CAS); however, the true clinical effect of single AP therapy vs DAPT is unknown. We examined the efficacy and safety of preoperative single AP therapy vs DAPT in patients who had undergone transfemoral CAS (tfCAS) or transcarotid artery revascularization (TCAR).
Methods: We identified all patients who had undergone tfCAS or TCAR in the Vascular Quality Initiative database from 2016 to 2021. We stratified the patients by procedure and identified those who had received the following preoperative AP regimens: DAPT (acetylsalicylic acid [ASA] + P2Y12 inhibitor [P2Yi]), no AP therapy, ASA only, ASA + AP loading dose, P2Yi only, and P2Yi + AP loading dose. The AP loading dose was given within 4 hours of CAS. We generated propensity scores for each treatment regimen and assessed in-hospital outcomes using inverse probability weighted log binomial regression, with DAPT as the reference and adjusting for intraoperative protamine use. The primary efficacy outcome was a composite end point of stroke and death, and the primary safety outcome was access-related bleeding.
Results: Of the 18,570 tfCAS patients, 70% had received DAPT, 5.6% no AP therapy, 10% ASA only, 8.0% ASA + AP loading dose, 4.6% P2Yi only, and 2.9% P2Yi + AP loading dose. The corresponding unadjusted rates of stroke/death were 2.2%, 6.8%, 4.1%, 5.1%, 2.4%, and 2.3%. After adjustment, compared with DAPT, the incidence of stroke/death was higher with no AP therapy (relative risk [RR], 2.3; 95% confidence interval [CI], 1.7-3.2), ASA only (RR, 1.6; 95% CI, 1.2-2.1), and ASA + AP loading dose (RR, 2.0; 95% CI, 1.5-2.7) but was similar with P2Yi only (RR, 0.99; 95% CI, 0.58-1.7) and P2Yi + AP loading dose (RR, 1.1; 95% CI, 0.49-2.5). Of the 25,459 TCAR patients, 81% had received DAPT, 2.0% no AP therapy, 5.5% ASA only, 3.5% ASA + AP loading dose, 4.9% P2Yi only, and 2.4% P2Yi + AP loading dose. The corresponding unadjusted rates of stroke/death were 1.5%, 3.3%, 3.3%, 2.9%, 1.2%, and 1.1%. After adjustment, compared with DAPT, the incidence of stroke/death was higher with no AP therapy (RR, 2.0; 95% CI, 1.2-3.3) and ASA only (RR, 2.2; 95% CI, 1.5-3.1), with a trend toward a higher incidence with ASA + AP loading dose (RR, 1.6; 95% CI, 0.99-2.6), and was similar with P2Yi only (RR, 0.98; 95% CI, 0.54-1.8) and P2Yi + AP loading dose (RR, 0.66; 95% CI, 0.27-1.6). No differences were found in the incidence of access-related bleeding between the treatment groups after tfCAS or TCAR.
Conclusions: Compared with DAPT, no AP therapy or ASA monotherapy was associated with higher rates of stroke/death after CAS and should be discouraged as unsafe practice. Meanwhile, P2Yi monotherapy was associated with similar rates of stroke/death. No differences were found in the incidence of bleeding complications, and adding an AP loading dose to ASA or P2Yi monotherapy within 4 hours of the procedure did not affect the outcomes. Overall, these findings support the current guidelines recommending DAPT before CAS but also suggest that P2Yi monotherapy might confer thromboembolic benefits similar to those with DAPT. However, an immediate preoperative AP loading dose might not provide additional thromboembolic benefits.
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http://dx.doi.org/10.1016/j.jvs.2022.12.034 | DOI Listing |
Bioconjug Chem
January 2025
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-5127, United States.
Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.
View Article and Find Full Text PDFClin Infect Dis
January 2025
Professor of Medicine, Director, Institute for Therapeutic Innovation at University of Florida, Orlando, FL, USA.
Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (f) (unbound) antibiotic concentrations remain above the Minimal Inhibitory Concentration (MIC), including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis and/or septic shock. These studies have yielded inconsistent results for patients as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies and the absence of Therapeutic Drug Monitoring (TDM).
View Article and Find Full Text PDFJ Am Podiatr Med Assoc
January 2025
‡Department of Plastic Surgery, Medstar Georgetown University Hospital, Washington, DC.
Background: The formation of heterotopic ossification (HO) is a common complication after transosseous partial foot amputation. Development of HO in weightbearing and/or superficial areas can lead to increased pressures, which increases the likelihood of wound formation and pain. Current treatment modalities for HO of the foot include mechanical off-loading and surgical resection; however, prophylactic measures such as nonsteroidal anti-inflammatory drugs, bisphosphonates, and other medical therapies have been attempted previously with mixed efficacy.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.
The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression.
View Article and Find Full Text PDFMol Ther
January 2025
Department of Surgery, University of California San Diego, La Jolla, CA, 92093, United States; Department of Dermatology, University of California San Diego, La Jolla, CA, 92093, United States. Electronic address:
Small extracellular vesicles (sEVs) mediate intercellular signaling to coordinate proliferation of cell types that promote re-epithelialization of skin following injury. Cyclin-dependent kinase 1 (CDK1) drives cell division and is a key regulator of entry to cell cycle. To understand the potential of sEV-mediated delivery of CDK1 to reverse impaired wound healing, we generated CDK1-loaded sEVs (CDK1-sEVs) and evaluated their ability to mediate cell proliferation, re-epithelialization and downstream signaling responses in the wound bed.
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