Preoperative aspirin and anticoagulants do not affect partial nephrectomy bleeding.

INTRODUCTION: Studies have reached mixed conclusions on the role of antiplatelet and anticoagulant agents on postoperative complications of partial nephrectomies. This study examines whether preoperative anticoagulation use affected the risk of hemorrhagic complications after partial nephrectomy. MATERIALS AND METHODS: This is a retrospective chart review of all partial nephrectomies performed between 2017 and 2022 at a single institution. For each operation, preoperative data was gathered on whether the patient was on anticoagulation, the type and dose of anticoagulation, and how many days the anticoagulation was held preoperatively. Bivariate analyses for continuous measures were performed using Student's t-tests when there were two comparison groups and ANOVA models when there were more than two comparison groups and Chi-Square tests were used for categorical variables, with Fisher's Exact being used when expected cell counts were small. RESULTS: In this study, warfarin was held for an average of 5.43 days, clopidogrel was held for an average of 6.60 days, aspirin was held for an average of 7.65 days, and direct oral anticoagulants (DOACs) were held for an average of 4.00 days. There was no significant difference in hemoglobin (Hb) change, rate of intraoperative transfusion, postoperative transfusion, bleeding complication, pseudoaneurysm rate, or additional bleeding processes between patients on prior anticoagulation therapy and those not on therapy. There was no significant difference in intraoperative or postoperative outcomes based on history of aspirin use and continuation of aspirin through the surgery. While estimated blood loss appeared statistically significant initially, this difference was accounted for by the covariates of comorbidities, RENAL score, surgical approach, and type of renorrhaphy. Overall, there was no difference in complication rate based solely on aspirin use or continuation of aspirin through surgery. CONCLUSIONS: No difference in complication rate of partial nephrectomy was determined to be solely due to prior use of anticoagulation or aspirin use alone with appropriate cessation of anticoagulation preoperatively. Overall, patients on anticoagulation are not at a higher risk of intraoperative or postoperative bleeding complications when undergoing partial nephrectomy.

Safety and complications of continuation of aspirin therapy in patients undergoing robot-assisted laparoscopic simple prostatectomy.

To evaluate the safety and feasibility of continued perioperative aspirin at the time of robotic assisted simple prostatectomy (RASP). We performed a retrospective review of our IRB approved institutional database of patients who underwent RASP between 2013 and 2022. Comparative groups included patients taking aspirin in the perioperative period and those not taking aspirin pre-operatively. The primary outcome was any post-operative bleeding related complication using the modified Clavien-Dindo classification. Secondary outcomes included the identification of risk factors for increased blood loss in the entire study population, operative time, and blood transfusion requirement. 143 patients underwent RASP of which 55 (38.5%) patients continued perioperative aspirin therapy and 88 (61.5%) patients did not. Baseline demographics were similar between groups. Patients taking perioperative aspirin had a higher rate of hypertension (74.5% vs 58.0%, p = 0.04) and other cardiovascular disease (30.9% vs 11.4%, p = 0.007). Postoperative complications were similar between the groups (Clavien-Dindo ≥ 3; p = 0.43). Median blood loss (150 cc vs 150 cc, p = 0.38), percentage drop in hemoglobin (13.4 vs 13.2, p = 0.94) and blood transfusion rate (3.6 vs 1.1, p = 0.56) were also similar between groups. The median blood loss was 150 ml for the whole study population. On regression analysis, neither aspirin nor any other variable was associated with increased blood loss (> 150 ml). Aspirin can be safely continued perioperatively in patients undergoing RASP without any risk of bleeding related complications, blood loss, or increased transfusion rate.

[Progress in application of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease].

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.

Aspirin for Metabolic Dysfunction-Associated Steatotic Liver Disease Without Cirrhosis: A Randomized Clinical Trial.

Importance: Aspirin may reduce severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown. Objective: To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD. Design, Setting, and Participants: This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023. Interventions: Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months. Main Outcomes and Measures: The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified. Results: Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was -6.6% with aspirin vs 3.6% with placebo (difference, -10.2% [95% CI, -27.7% to -2.6%]; P = .009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (-8.8 vs 30.0 percentage points; mean difference, -38.8 percentage points [95% CI, -66.7 to -10.8]; P = .007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P = .006), reduced absolute hepatic fat content by MRI-PDFF (-2.7% vs 0.9%; mean difference, -3.7% [95% CI, -6.1% to -1.2%]; P = .004]), and reduced relative hepatic fat content by MRI-PDFF (-11.7 vs 15.7 percentage points; mean difference, -27.3 percentage points [95% CI, -45.2 to -9.4]; P = .003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn. Conclusions and Relevance: In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04031729.

Aspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways.

Aspirin is a non-steroidal, anti-inflammatory drug often used long term. However, long-term or large doses will cause gastrointestinal adverse reactions. To explore the mechanism of intestinal damage, we used non-targeted metabolomics; farnesoid X receptor (FXR) knockout mice, which were compared with wild-type mice; FXR agonists obeticholic acid (OCA) and chenodeoxycholic acid (CDCA); and endothelin-producing inhibitor estradiol to explore the mechanisms of acute and chronic intestinal injuries induced by aspirin from the perspective of molecular biology. Changes were found in the bile acids taurocholate acid (TCA) and tauro-ß-muricholic acid (T-ß-MCA) in the duodenum, and we detected a significant inhibition of FXR target genes. After additional administration of the FXR agonists OCA and CDCA, duodenal villus damage and inflammation were effectively improved. The results in the FXR knockout mice and wild-type mice showed that the overexpression of endothelin 1 (ET-1) was independent of FXR regulation after aspirin exposure, whereas CDCA was able to restore the activation of ET-1, which was induced by aspirin in wild-type mice in an FXR-dependent manner. The inhibition of ET-1 production could also effectively protect against small bowel damage. Therefore, the study revealed the key roles of the FXR and ET-1 pathways in acute and chronic aspirin-induced intestinal injuries, as well as strategies on alleviating aspirin-induced gastrointestinal injury by activating FXR and inhibiting ET-1 overexpression.

Protective Effects of Aspirin Supplemented With Quercetin in L-NAME-Induced Preeclampsia-Like Rats.

Aspirin supplemented with quercetin was reported to enhance the therapeutic effects of aspirin in a rat model of preeclampsia. In this study, the underlying mechanisms were further explored. Preeclampsia was induced by L-NAME (50 mg/kg/day) via oral gavage from gestation day (GD)14 to GD19. Aspirin (1.5 mg/kg/day) administration was performed using aspirin mixed with rodent dough from GD0 to GD19. The administration of quercetin (2 mg/kg/day) was performed by intraperitoneal infusion from GD0 to GD19. Protein levels were evaluated using ELISA or Western blot, and microRNA (miRNA) level was evaluated by RT-PCR. Aspirin supplemented with quercetin ameliorated the increase of systolic blood pressure (SBP), proteinuria, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, and improved the pregnancy outcomes in preeclampsia rats. Aspirin supplemented with quercetin inhibited miR-155 expression in preeclampsia rats. The decreased miR-155 level in placenta further increased the protein level of SOCS1 and inhibited the phosphorylation of p65. In this study, we demonstrated that aspirin supplemented with quercetin enhanced the effects of aspirin for the treatment of preeclampsia.

Monotherapy with P2Y12-inhibitors after dual antiplatelet therapy: Filling gaps in evidence.

BACKGROUND: Whether P2Y12 inhibitor monotherapy (P2Y12-I) is superior to aspirin following DAPT discontinuation post-PCI remains to be established. METHODS: We updated our prior network meta-analysis where P2Y12-I and aspirin had been compared with DAPT or directly with each other. The focus is specifically on the available direct evidence, now consisting of the three head-to-head comparisons of P2Y12-I and aspirin in event-free PCI patients after DAPT. We include a Trial Sequential Analysis of the direct evidence based on meta-analytical literature. RESULTS: The main finding reveals a 39% significantly lower risk of myocardial infarction with P2Y12-I (RR 0.61, 95% CI 0.47-0.78, p = 0.0001, I2 = 0%) with no difference in bleeding. Trial Sequential Analysis demonstrates clinically meaningful evidence for a reduction in the incidence of myocardial infarction with P2Y12-I that is also supported by statistical significance. CONCLUSIONS: Accruing data highlight that P2Y12-I following DAPT discontinuation after PCI is associated with lower risk for MI and a similar risk for bleeding as compared with ASA. In light of potential limitations to the widespread adoption of life-long P2Y12-I treatment, clinicians should consider identifying selected patients who are expected to derive the highest benefit.

Aspin: neurosurgical aspirin intervention prognostic study - perioperative continuation versus discontinuation of aspirin in lumbar spinal surgery, a randomized controlled, noninferiority trial.

RATIONALE: Aspirin is typically discontinued in cranial and spinal surgery because of the increased risk of hemorrhagic complications, but comes together with the risk of resulting in an increase of cardiac and neurologic thrombotic perioperative events. OBJECTIVE: The aim of this study is to investigate the non-inferiority of perioperative continuation of aspirin patients undergoing low complex lumbar spinal surgery, compared with the current policy of perioperative discontinuation of aspirin. STUDY DESIGN: A randomized controlled trial with two parallel groups of 277 cases (554 in total). STUDY POPULATION: Patients undergoing low complex lumbar spinal surgery and using aspirin. All patients are aged >18 years. INTERVENTION: Peri-operative continuation of aspirin. STUDY OUTCOMES: Primary study outcome: composite of the following bleeding complications: Neurological deterioration as a result of hemorrhage in the surgical area with cauda and/or nerve root compression. Post-surgical anemia with hemoglobin level lower than 5 mmol/l, requiring transfusion. Subcutaneous hematoma leading to wound leakage and pain higher than NRS=7. Major and/or minor hemorrhage in any other body system according to the definition of the International Society on Thrombosis and Haemostasis bleeding scale. Secondary study outcomes: Each of the individual components of the primary outcome Absolute mean difference in operative blood loss between the study arms Thrombo-embolic-related complications: Myocardial infarction Venous thromboembolism Stroke Arterial thromboembolism FURTHER STUDY OUTCOMES: Anticoagulant treatment satisfaction by the Anti-Clot Treatment Scale (ACTS) and general health by the Patient-Reported Outcomes Measurement Information System (PROMIS Global-10) in the pre- and postoperative phase. NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT, AND GROUP RELATEDNESS: Participation in this study imposes no additional risk to patients. Currently, there is no consensus on whether or not aspirin should be discontinued before cranial or spinal surgery. Currently, aspirin is typically discontinued in cranial and spinal surgery, because of a potential increased risk of hemorrhagic complication. An argument not based on a clinical trial. However, this policy might delay surgical procedures or carry the risk of resulting in an increase in cardiac and neurologic thrombotic perioperative events. It is unclear if the possibility of an increase in hemorrhage-related complications outweighs the risk of an increase in cardiac and neurologic thrombotic perioperative events. Furthermore, the Data Safety Monitoring Board (DSMB) will be asked for safety analysis by monitoring the study. There are no further disadvantages to participating in this study. Outcome measurements are recorded during admission and regular outpatient visits, and thus, do not require additional visits to the hospital.

Low-dose aspirin use and risk of ovarian cancer: a combined analysis from two nationwide studies in Denmark and Sweden.

BACKGROUND: Studies on association between low-dose aspirin use and ovarian cancer risk were mostly based on self-reported medication use and few had large enough sample size to investigate the potential modification effect by ovarian cancer risk factors. METHODS: In these two nationwide nested case-control studies among the Danish and Swedish female population, 11,874 women with ovarian cancer (30-84 years old) (Denmark: 7328 diagnosed in 2000-2019, Sweden: 4546 diagnosed in 2010-2018) were randomly age- matched with 473,960 female controls (293,120 from Denmark, and 181,840 from Sweden). We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and combined the estimates based the fixed-effect assumption. Effect modification by inflammation-related risk factors and by indication (cardiovascular disease, CVD) were also investigated. RESULTS: Ever use of low-dose aspirin was not strongly associated with the overall risk of ovarian cancer (OR = 0.97; 95%CI: 0.92-1.03). However, the association differed according to parity (nulliparous: OR = 0.80, 95%CI: 0.70-0.92; parous: OR = 1.00, 95%CI: 0.94-1.07; p-interaction = 0.0024), and according to history of CVD (no CVD: OR = 0.91, 95%CI: 0.82-1.00; ever CVD: OR = 1.05, 95%CI: 0.97-1.13; p-interaction =0.0204). CONCLUSIONS: Low-dose aspirin use was associated with a decreased ovarian cancer risk especially in nulliparous women and in women without CVD diagnosis.

Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women.

PURPOSE: One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts. METHODS: Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay. RESULTS: After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF. CONCLUSIONS: ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted. Trial registration EudraCT: 2017-000317-22.

Aspirin is as effective as low molecular weight heparins in preventing symptomatic venous thromboembolism following arthroscopic anterior cruciate ligament reconstruction.

OBJECTIVE: The optimal agent for thromboprophylaxis following arthroscopic anterior cruciate ligament reconstruction (ACLR) remains unclear, particularly in patients with a low baseline risk for venous thromboembolism (VTE). This retrospective cohort study aims to compare the effectiveness and safety of aspirin versus low molecular weight heparins (LMWHs) in this specific patient population. METHODS: We analyzed data from patients who underwent ACLR between March 2016 and March 2021, focusing on those with a low risk for VTE. High-risk individuals, identified by factors such as cardiac disease, pulmonary disease, diabetes mellitus, previous VTE, inflammatory bowel disease, active cancer, and a BMI > 40, were excluded (n = 33). Our approach included a thorough review of medical charts, surgical reports, and pre-operative assessments, complemented by telephone follow-up conducted over a 3-month period by a single investigator. We assessed the incidence of symptomatic VTE, including deep vein thrombosis and pulmonary thromboembolism, as the primary outcome. The secondary outcomes included to complications related to the surgery and thromboprophylaxis. Statistical analysis included descriptive statistics, univariate logistic regression models, and calculations of incidence rates. RESULT: In our study, 761 patients (761 knees) were included, with 458 (60.18%) receiving aspirin and 303 (39.82%) receiving LMWH. The two groups showed no significant differences in demographic factors except for age. The incidence of VTE was reported at 1.31% (10 individuals). Specifically, five patients in the aspirin group (1.09%) and five patients in the LMWH group (1.65%) developed a symptomatic VTE event (p = 0.53). Additionally, the two groups did not significantly differ in terms of other complications, such as hemarthrosis or surgical site infection (p > 0.05). Logistic regression analysis revealed no statistically significant difference in VTE risk between the two groups. CONCLUSION: This study, focusing on isolated ACLR in patients with a low baseline risk for venous thromboembolism, demonstrated that aspirin is equally effective as low molecular weight heparins for VTE prophylaxis following this surgery. LEVEL OF EVIDENCE: III.

Aspirin prophylaxis is not associated with increased risk of venous thromboembolism in arthroplasty for femoral neck fractures: a non-inferiority study.

PURPOSE: Venous thromboembolism (VTE) is a known complication of hip arthroplasty for femoral neck fractures (FNF) with various prophylactic anticoagulants utilized to decrease risk. The purpose of this study was to assess the efficacy and perioperative outcomes associated with aspirin for VTE prophylaxis following arthroplasty for FNF. METHODS: Medical records of 1,220 patients who underwent hip hemiarthroplasty (HHA) or total hip arthroplasty (THA) at an urban academic center from 2011 to 2022 were retrospectively reviewed. Patient characteristics and perioperative outcomes, including length of stay (LOS), VTE, 90-day hospital encounters, and discharge disposition, were collected. Outcomes for patients prescribed aspirin (n = 214) were compared to those prescribed non-aspirin VTE prophylaxis (n = 1006) using propensity score matching. RESULTS: Patients who received aspirin had higher rates of THA (36.0 vs 26.7%; p = 0.008). There were no significant risk-adjusted differences in the incidence of VTE (0.5 vs 0.5%, p = 1.000) and 90-day readmissions (10.4 vs 12.3%, p = 0.646) between patients prescribed aspirin and non-aspirin VTE prophylaxis, respectively. Patients prescribed non-aspirin agents had higher rates of non-home discharge (73.9 vs 58.5%; p < 0.001) and longer LOS (143.5 vs 124.9 h; p = 0.005). Sub-analysis of patients prescribed aspirin and non-aspirin prophylaxis based on comorbidity scores demonstrated no difference in VTE incidence for low (0.0 vs 1.6%, p = 1.000) and high scores (0.0 vs 0.0%, p = 1.000), respectively. CONCLUSION: Aspirin is not associated with increased incidence of VTE after HHA or THA for FNF. Aspirin prophylaxis should be considered in hip fracture patients to mitigate bleeding risk, particularly those with low to intermediate VTE risk. LEVEL OF EVIDENCE: Level III, Retrospective study.

Mast Cells in Aspirin-Exacerbated Respiratory Disease.

PURPOSE OF REVIEW: Aspirin-exacerbated respiratory disease (AERD) is a syndrome of high type 2 inflammation and is known to critically involve mast cell activation. The mast cell is an important cell in the baseline inflammatory processes in the upper and lower airway by maintaining and amplifying type 2 inflammation. But it also is prominent in the hypersensitivity reaction to COX-1 inhibition which defines this condition. RECENT FINDINGS: Recent work highlights the mast cell as a focal point in AERD pathogenesis. Using AERD as a specific model of both high type 2 asthma and chronic sinusitis, the role of mast cell activity can be better understood in other aspects of airway inflammation. Further dissecting out the mechanism of COX-1-mediated mast cell activation in AERD will be an important next phase in our understanding of NSAID-induced hypersensitivity as well as AERD pathophysiology.

Prolonged Proton Pump Inhibitor Use and Thrombohemorrhagic Risk in Essential Thrombocythemia and Polycythemia Vera Patients Treated with Long-Term Aspirin: A Pilot Study.

INTRODUCTION: Proton pump inhibitors (PPIs) are known to decrease the risk of gastrointestinal (GI) bleeding. However, concerns have been raised regarding the potential pharmacodynamic interactions of PPIs and antiplatelet drugs with respect to cardiovascular risk. Patients with BCR::ABL1-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), and polycythemia vera (PV) often suffer from peptic ulcer disease (PUD) and frequently receive low-dose aspirin due to an intrinsically high thrombotic risk. METHOD: This retrospective multicenter study from a community setting investigated whether continuous PPI use may affect thrombohemorrhagic risk in ET and PV patients treated with long-term aspirin. RESULTS: Ninety-four aspirin-treated MPN patients (ET = 36, PV = 58) were included; median age was 69.5 years (range 21-92) and 40 (42.6%) were males. Nineteen (20.2%) patients continuously received PPIs and pantoprazole (n = 15, 78.9%) was the most frequently received PPI. PV phenotype (p = 0.085), male sex (p = 0.011), and prior thrombosis (p = 0.005) were associated with PPI use, whereas no correlations were found with respect to age, disease risk, splenomegaly, mutational status, constitutional symptoms, cardiovascular risk factors, cytoreductive treatment, or any of the blood cell counts (p > 0.050 for all analyses). The median follow-up time was 55.5 months; 19 (20.2%) thrombotic and 13 (13.8%) bleeding events occurred during this time. The use of PPIs was not associated with an increased risk of thrombosis (p = 0.158) or overall bleeding (p = 0.229) and none of the patients treated with PPIs experienced GI bleeding. CONCLUSIONS: Considering that Helicobacter pylori infection and PUD are quite frequent in ET and PV patients, these preliminary results may provide some reassurance to physicians regarding the absence of thrombohemorrhagic risk associated with prolonged PPI use in MPN patients treated with long-term aspirin. Our observations may be even more important in the light of recent evidence suggesting suboptimal platelet inhibition in ET with once-daily when compared to twice- or triple-daily aspirin which may also cause more abdominal discomfort. Limitations of this study are its retrospective design, limited number of patients included, and the lack of pharmacodynamic and pharmacokinetic assessments.

Not just snot: Local inflammatory profiles in patients with aspirin-exacerbated respiratory disease differ from patients with aspirin-tolerant chronic rhinosinusitis.

KEY POINTS: IL-5, CCL2, and CXCL8 in sinus mucous are higher in patients with AERD relative to aspirin-tolerant patients with CRS These mediators are pleiotropic, leading to widescale inflammatory processes contributing to AERD AERD is not only a T2 disease but heterogeneous: this may explain the refractory nature of AERD.

Nasal polyp antibody-secreting cells display proliferation signature in aspirin-exacerbated respiratory disease.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) causes nasal obstruction and olfactory dysfunction. Aspirin-exacerbated respiratory disease (AERD) is the triad of CRSwNP, asthma, and respiratory reactions to COX-1 inhibitors. Patients with AERD have elevated nasal IL-5 levels and high numbers of antibody-secreting cells (ASCs), including plasma cells and plasmablasts, in their polyp tissue; in addition, their nasal polyp (NP) IgE levels are correlated with disease severity and recurrence of nasal polyposis. OBJECTIVE: We sought to explore differences in the transcriptomic profile, activation markers, and IL-5Rα expression and function of NP ASCs from patients with AERD and CRSwNP. METHODS: NP tissue was collected from patients with AERD and CRSwNP and digested into single-cell suspensions. NP cells were analyzed for protein expression by mass cytometry. For IL-5Rα functional studies, plasma cells were purified and cultured in vitro with or without IL-5 and analyzed by bulk RNA sequencing. RESULTS: Compared with polyp tissue from patients with CRSwNP, polyp tissue from patients with AERD contained significantly more ASCs and had increased ASC expression of IL-5Rα. ASCs from patients with AERD expressed higher protein levels of B-cell activation and regulatory markers (CD40, CD19, CD32, and CD38) and the proliferation marker Ki-67. ASCs from patients with AERD also expressed more IL5RA, IGHE, and cell cycle- and proliferation-related transcripts (CCND2, MKI67, CDC25A, and CDC25B) than did ASCs from patients with CRSwNP. Stimulation of plasma cells from patients with AERD with IL-5 induced key cell cycle genes (CCND2 and PTP4A3), whereas IL-5 stimulation of ASCs from patients with CRSwNP induced few transcriptomic changes. CONCLUSION: NP tissue ASCs from patients with AERD express higher levels of functional IL-5Rα and markers associated with cell cycling and proliferation than do ASCs from patients with aspirin-tolerant CRSwNP.

An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

Optimal antiplatelet strategy following coronary artery bypass grafting: a meta-analysis.

OBJECTIVE: Coronary artery bypass grafting (CABG) is an established revascularisation strategy for multivessel and left main coronary artery disease. Although aspirin is routinely recommended for patients with CABG, the optimal antiplatelet regimen after CABG remains unclear. We evaluated the efficacies and risks of different antiplatelet regimens (dual (DAPT) versus single (SAPT), and dual with clopidogrel (DAPT-C) versus dual with ticagrelor or prasugrel (DAPT-T/P)) after CABG. METHODS: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and performed a comprehensive literature search using PubMed, Ovid Medline, Ovid Embase and Cochrane Central Register of Controlled Trials. Data were extracted and pooled using random-effects models and Review Manager (V.5.4). RESULTS: Among the 2970 article abstracts screened, 215 full-text articles were reviewed and 38 studies totaling 77 447 CABG patients were included for analyses. DAPT compared with SAPT was associated with significantly lower all-cause mortality (OR 0.65 with 95% CI 0.50 to 0.86; p=0.002), cardiovascular mortality (OR 0.53, 95% CI 0.33 to 0.84; p=0.008), and major adverse cardiac and cerebrovascular events (MACCE) (OR 0.68, 95% CI 0.51 to 0.91; p=0.01), but higher rates of major (OR 1.30, 95% CI 1.08 to 1.56; p=0.007) and minor bleeding (OR 1.87, 95% CI 1.28 to 2.74; p=0.001) after CABG. DAPT-T/P compared with DAPT-C was associated with significantly lower all-cause (OR 0.43, 95% CI 0.29 to 0.65; p≤0.0001) and cardiovascular mortality (OR 0.44, 95% CI 0.24 to 0.80; p=0.008), and no differences on other cardiovascular or bleeding outcomes after CABG. CONCLUSION: In patients with CABG, DAPT compared with SAPT and DAPT-T/P compared with DAPT-C were associated with reduction in all-cause and cardiovascular mortality, especially in patients with acute coronary syndrome. Additionally, DAPT was associated with reduction in MACCE, but higher rates of major and minor bleeding. An individualised approach to choosing antiplatelet regimen is necessary for patients with CABG based on ischaemic and bleeding risks.

Is it Safe to Continue Aspirin in Patients Undergoing Percutaneous Nephrolithotomy?

OBJECTIVE: To evaluate peri-operative outcomes in patients on chronic aspirin therapy undergoing percutaneous nephrolithotomy (PCNL), with and without discontinuation of aspirin. Anti-coagulation and anti-platelet therapy are contraindications for PCNL per American Urological Association guidelines due to bleeding risk. However, there is potentially increased cardiovascular risk with peri-procedural aspirin withdrawal. METHODS: Patients on chronic aspirin undergoing PCNL between January 2014 and May 2019 were retrospectively reviewed and stratified by continued or discontinued aspirin >5 days preoperatively. Hematologic complications, transfusions, and thrombotic complications were assessed with logistic regression model. RESULTS: Three hundred twenty-five patients on chronic aspirin therapy underwent PCNL-85 continued and 240 discontinued aspirin. There were no significant differences in hemoglobin change, estimated blood loss, transfusions, creatinine change, thrombotic complications, 30-days re-admissions, complications, or 30-day emergency department visits. Patients who continued aspirin had longer length of stay (1.6 vs 1.9 days, P = .03). American Society of Anesthesiologists (ASA) score of 3 (OR 3.2, P = .02, 95% confidence intervals (CI) [1.2-8.4]), ASA score of 4 (OR 4.0, P = .02, 95% CI [1.2-13.1]), Black race, and previous smoking (OR 2.1, P = .02, 95% CI [1.1-3.9]) was associated with continued aspirin. Body mass index ≥30 was associated with aspirin discontinuation (OR 0.9, P = .004, 95% CI [0.9-1.0]). Increased postoperative hematologic complications were associated with additional anticoagulation medication (OR 2.9, P = .04, 95% CI [1.0-4.4]). CONCLUSION: Continued aspirin use did not increase in postoperative complications in patients undergoing PCNL. Patients who are on additional anticoagulation medication are at risk of hematologic complications.

Should Biologics Be Used Before Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease?

There has been a paradigm shift in the management of aspirin-exacerbated respiratory disease (AERD). It started in 2015 when the first biologic was Food and Drug Administration (FDA) approved for severe eosinophilic asthma. Thus, there emerged a new era in the treatment of patients with type 2-mediated airway diseases. This has led to an increasing number of options for patients, undoubtably a great thing, but has left clinicians without a clear answer for how to balance the therapies that exist for AERD, what to recommend for treatment, and how to best assess the benefits and risks of each therapy. This paper aims to explore these benefits and risks, and to provide a roadmap for future studies.