Effect Of Aspirin Research Articles

Effects of aspirin and omega-3 fatty acids on composite and subdomain scores from the NEI-VFQ-25 questionnaire: the ASCEND-Eye randomized controlled trial

BackgroundThe double-blind, 2 × 2 factorial design, placebo-controlled ASCEND randomized trial compared the effects of 100 mg aspirin daily and, separately, 1 g omega-3 fatty acids (FAs) daily on the primary prevention of cardiovascular disease in 15,480 UK adults with diabetes. We report the effects of these randomized treatment allocations on scores derived from the National Eye Institute’s Visual Function Questionnaire-25 (NEI-VFQ-25) in a subset of participants involved in the ASCEND-Eye sub-study.MethodsOrdinal data from the NEI-VFQ-25 were analyzed using proportional odds regression methods. A common odds ratio with a 95% confidence interval was used to interpret the average effect size of randomization to each study treatment on composite and subdomain scores from the questionnaire.ResultsNeither randomization to aspirin nor omega-3 FAs for 7.5 years significantly affected composite or subdomain scores from the NEI-VFQ-25.ConclusionApplying the NEI-VFQ-25 in ASCEND-Eye represents one of the largest surveys of vision-targeted health-related quality of life in people with diabetes. Further observational analyses of these data are planned, to identify the clinical and demographic characteristics associated with lower composite and subdomain scores in a diabetic population.Trial registrationEudract No. 2004–000991-15; Multicentre Research Ethics Committee Ref No. 03/8/087 (29th December 2003); ClinicalTrials.gov No. NCT00135226 (24th August 2005); ISRCTN No. ISRCTN60635500 (1st September 2005).

Uncovering patients’ preferences for brand among essential classes of coronary heart disease medications using a discrete choice experiment

Patient preferences for medications strongly correlate with adherence; one area of interest is the choice between branded and generic drugs. Despite extensive research about brand-versus-generic drug preferences, few studies have explored severe-illness patients like those with coronary heart disease (CHD). We could not locate studies measuring preference weights of branded drugs in different classes within guideline-recommended regimens using discrete choice experiments (DCE). We aimed to explore the preference for branded medications used for secondary prevention of CHD events among patients receiving treatment at one of the largest Egyptian health insurance clinics. Patients with CHD were interviewed to choose between various therapy regimens containing brand-name and generic versions of aspirin, beta-blockers, statins, and renin–angiotensin–aldosterone system blockers (RAAS blockers). The study employed a DCE technique and followed the recommendations of the International Society of Pharmacoeconomics and Outcomes Research (ISPOR). Seventy-two percent (149) of the 208 patients questioned were dissatisfied with at least one of their generic medications. The majority of unsatisfied patients displayed brand preferences across the four medicine classes, primarily due to the notion that generics may be less effective. Patients preferred the RAAS blocker brand the most (adjusted odds ratio [AOR]: 3.14; 95% confidence interval [CI] 2.83 to 3.48), followed by beta-blockers (AOR: 2.06; 95% CI 1.88 to 2.27) and statins (AOR: 1.5; 95% CI 1.50 to 1.61). The relative importance of each class from the patient’s perspective showed the highest importance with RAAS blockers (22.2%) and beta-blockers (14.1%), while statins and aspirin had minor importance (7.8% and 6.6%, respectively). In the present study, branded drugs for secondary CHD prevention were preferred over generic alternatives. This finding has two implications for clinical practice. Firstly, physicians and pharmacists need to assure patients about the quality of generics to insure patient satisfaction and adherence to medication. Secondly, health insurance providers need to confirm the effectiveness of generics through observational studies. Despite the well-proven protective effects of aspirin and statins, they had minor importance from the patient’s perspective, highlighting the need to enhance patient knowledge. DCE was demonstrated to be a useful tool for eliciting the genuine preferences of patients treated within the setting of health insurance.

Effect of low-dose aspirin on mid-luteal phase uterine Artery blood flow in women with unexplained recurrent pregnancy loss

Objectives: As a possible therapy for recurrent pregnancy loss, this study sought to ascertain if low-dose aspirin was effective in increasing uterine artery blood flow. Study Design: This investigation was structured as a single-arm clinical trial Patients and Methods: All participants were aged 39 years or younger and had no prior or current indications of abnormal glucose tolerance, thyroid dysfunction, hyperprolactinemia, or Antiphospholipid antibody syndrome. Bilateral assessments of the Systolic/Diastolic (S/D) ratio, Resistive Index (RI), and Pulsatility Index (PI) were conducted in the chosen patients in the mid-luteal phase, before to and following a minimum of two weeks of low-dose aspirin administration. Results: The results of this investigation showed significant variation in the S/D and PI prior to and following aspirin administration. There was no discernible shift in RI. The analysis revealed a statistically significant reduction in uterine artery PI after aspirin administration (1.92±0.29) compared to the pre-treatment value (2.22±0.27), with a p-value of 0.0001. Remarkably, the pulsatility indices of the left and right uterine arteries did not significantly differ from one another. Conclusion: For women who have a history of miscarriages, low-dose aspirin can be recommended as an adjuvant therapy as it effectively improves uterine artery blood flow in these patients. However, more well-designed research is required to ascertain whether improved pregnancy outcomes are correlated with improved uterine perfusion. The current study supported the aspirin guideline for women with a history of recurrent miscarriages by showing that aspirin treatment resulted in a reduction in uterine artery PI.

Metabolomics revealed pharmacodynamic effects of aspirin and indobufen in patients after percutaneous transluminal angioplasty surgery

IntroductionAspirin and indobufen are commonly used therapeutic drugs for the prevention of vascular restenosis (VR) after percutaneous transluminal angioplasty surgery. They both exhibited antiplatelet effects but molecular mechanisms underlying metabolic changes induced by them remain unclear.MethodsIn this study, we collected plasma samples from patients on aspirin medication (n = 5), patients on indobufen medication, patients with no medication after PTA, and healthy controls (CKs) (n = 5). Our investigation aimed to reveal the metabolic processes in patients during vascular restenosis and its amelioration through drug therapy using liquid chromatography-tandem mass spectrometry (LC-MS/MS).ResultsOur data showed significant alterations in amino acid and choline metabolism in patients without medication after PTA. Aspirin and indobufen were able to regulate these metabolic pathways to alleviate VR symptoms. We identified several characteristic amino acids, including pro-leu, L-citrulline, his-glu, and L-glutamate, as important biomarkers for VR assessment in patients without medication after PTA. A total of 17 and 4 metabolites involved in arginine and phenylalanine metabolism were specifically induced by aspirin and indobufen, respectively. Their expression levels were significantly regulated by aspirin or indobufen, nearly reaching normal levels.DiscussionTaken together, our identification of metabolites involved in metabolic changes affected by aspirin and indobufen medication enhances the understanding of VR pathology after PTA. This may help identify early diagnostic biomarkers and therapeutic targets

Aspirin inhibits atherosclerosis through macrophage pyroptosis by interacting with Lactobacillus johnsonii and its metabolite butyrate

Abstract Introduction Atherosclerotic cardiovascular disease (ASCVD) is a chronic progressive disease closely related to metabolism and inflammation. Aspirin inhibits cyclooxygenase (COX) and has antiplatelet aggregation effects, considered as the cornerstone of ASCVD treatment. Numerous studies have shown that gut microbiota (GM) and its metabolites affects host metabolism. Studies have also shown that people taking aspirin exhibit specific changes in the microbiota profile. However, whether the interaction of aspirin with GM and its metabolites affects the therapeutic efficacy of aspirin in treating atherosclerosis (AS) have not been reported. Purpose This study aimed to explore the interaction of aspirin with the GM and its metabolites in the treatment of AS, to reveal the specific mechanism of the GM-metabolite axis and provide potential new targets for the combined treatment of AS. Methods To establish the mouse model of atherosclerosis by high-fat diet, and the atherosclerotic plaque burden and composition were analyzed. The role of GM in aspirin anti-atherosclerosis was explored by antibiotics and fecal microbiota transplantation (FMT). The third generation 16S RNA sequencing was used to explore the effects of aspirin on species diversity and abundance of GM, and to screen differential microorganisms for intervention of AS mice. UHPLC-MS and GC-MS were used to explore the changes of intestinal metabolites induced by aspirin. The correlation between gut microbiota and metabolites was also investigated. Finally, in vitro and in vivo experiments were performed to confirm the effects and mechanisms of metabolites on macrophage pyroptosis and atherosclerosis. Results Aspirin has anti-atherosclerosis effect. After removing gut microbiota, the therapeutic effect of aspirin on atherosclerosis was decreased. Three generations of 16S rRNA gene sequencing results showed that aspirin supplementation alters the diversity of gut microbiota, and increased the relative abundance of Lactobacillus johnsonii(L.johnsonii) and Ligilactobacillus murinus(L.murinus). After gavage of L.johnsonii and L.murinus, the plaque burden and macrophage pyroptosis were significantly reduced in AS mice. Colonization with L.johnsonii and L.murinus significantly increased the abundance of probiotics and butyrate level in the feces of AS mice and L.johnsonii and L.murinus were positively correlated with butyrate. Supplementation of butyrate inhibited macrophage pyroptosis and atherosclerosis in vivo. In vitro, butyrate could inhibit the expression of NLRP3/Caspase-1/IL-1β and pyroptosome production, and this process mainly by activating butyrate receptors GPR41, GPR43 and GPR109A. Conclusions The gut microbiota may mediate the anti-AS effect of aspirin by promoting an increase in the abundance of L.johnsonii and L.murinus. Butyrate produced by Lactobacillus may mediate the anti-AS effect of aspirin, and inhibiting macrophage pyroptosis and the progression of AS.

Major bleeding complications and antithrombotic treatment after isolated surgical bioprosthetic aortic valve replacement

Abstract Background Despite advancements in surgical techniques and perioperative care, post-operative bleeds and stroke remain significant concerns after bioprosthetic surgical aortic valve replacement (SAVR). Purpose We assessed the incidence of short-term (30d) and long-term major bleeds and strokes and their relations to antithrombotic treatment after isolated bioprosthetic SAVR. Methods The CAREAVR study included 721 patients who underwent isolated SAVR at four Finnish university hospitals between 2002 and 2014. The day-to-day information on short-term antithrombotic treatment was available from a subgroup including 227 patients, of whom 138 (60.7%) had preoperative aspirin. Preoperative aspirin was usually discontinued the day before the index surgery. Enoxaparin 1mg/kg twice daily and vitamin K antagonist (VKA) were routinely initiated on the first postoperative day, and enoxaparin continued until the INR remained at a therapeutic level ≥ 2.0 for two days. The routine duration of VKA treatment after surgery was 3 months. Results The median follow-up time was 4.9 (interquartile range 3.0–7.0) years. During the short-term 30-day period, 31 (4.3%) patients had a major bleed, and 13 (1.8%) patients experienced a major stroke. A vast majority of the bleeding (80.6%) occurred within two days after the surgery, and the tail effect of preoperative aspirin (5-7d) was present in 51.6% of episodes, indicating unintentional triple antithrombotic therapy. During the long-term follow-up (>30d after the index surgery), 40 (5.5%) major bleeding episodes occurred, and 47 (6.5%) patients experienced a major stroke. Overall, 23 (57.5%) of the patients with major bleeding were on OAC during the event. In addition, 13 (27.7%) of the patients experiencing major stroke during the long-term follow-up were on OAC during the event. Conclusions Compared to major strokes, the incidence of perioperative major bleeds was over twofold, the majority occurring during the tail effect of preoperative aspirin. During the long-term follow-up, the risks of stroke and bleeding were equal, and the majority of bleeding episodes appeared during anticoagulation treatment.

Long-term validation of AtherosSlerosis CardioVascular Disease (ASCVD) risk score and the role of aspirin for primary Cardiovascular prevention in Korean patients with over ASCVD 20% risk score

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death worldwide. The ASCVD risk score can be a great tool for preventing ASCVD in the future. There is a mediation recommendation depending on calculated risk called United States Prevention Services Task Force (USPSTF) aspirin (ASA) recommendation. However, the validation studies of long-term clinical outcomes in Korean population using the ASCVD risk score and of the effect of ASA in Korean patients using USPSTF recommendation are limited. Methods A total of 7,249 patients with any chest pain who underwent coronary spasm provocation tests between January 2004 and December 2021 were enrolled. Patients were divided into four groups, based on the ASCVD risk score: < 5% group (Low Risk, n = 2,534), 5 - 10% group (Borderline Risk, n=1,681), 10 - 20% group (Intermediate Risk, n = 1,896) and ≥ 20% group (High Risk, n = 1,138). The primary endpoint was Major Adverse Cerebral and Cardiovascular Event (MACCE1), including stroke and MACE. The secondary endpoint was MACCE 2, defined as composite of MACE and recurrent angina requiring follow-up coronary angiography (CAG). The third endpoint was the effect of aspirin in patients who have over 20% ASCVD risk. Results Long term (10-year) ASCVD risk score was well-validated from the "Low Risk" group to the "High Risk" group by 1.87%, 7.44%, 14.09%, and 30.61%, respectively (P < 0.001). In baseline characteristics, the calculation factors of ASCVD risk score is also well-stratified, showing the more adverse clinical profiles in the "High Risk" group than the "Low Risk" group. In 10-year clinical outcomes, although MACCE1 and MACCE2 showed an increasing trend numerically, stroke was observed to significantly increase according to ASCVD risk score. There was no effect of ASA prescribed in accordance with USPSTF recommendation. The group with the highest rate of 20% or more failed to show the aspirin prevent effect on the occurrence of CV events, but also increased the incidence (MACCE1; HR: 1.647, P-Value: 0.283, 95% CI: 0.662 - 4.100, MACCE2; HR: 1.819, P-Value: 0.025, 95% CI: 1.078 - 3.068). Conclusion Long term ASCVD risk score was associated with higher risk of stroke. However, MACCE1 and MACCE2 only showed an increasing trend numerically. Furthermore, the effect of ASA prescribed based on the USPSTF ASA use recommendation statement were not observed in Korean population. Consequently, additional research is needed to ensure the utility of ASCVD risk score and the effect of ASA in high-risk patients to prevent future CV events in Korean population.

Effect of aspirin on platelet-rich plasma of diabetes mellitus with lower extremity atherosclerosis.

Aim: Platelet-rich plasma (PRP), enriched with multiple growth factors, is a promising adjunctive therapy for diabetic foot ulcers (DFUs). As a classic anti-platelet drug for diabetic patients, the effects of aspirin on the content of growth factors in PRP remains unclear.Methods: Our study enrolled diabetic patients who were currently taking or not taking aspirin as the research subjects, with healthy volunteers as the control. PRP from these individuals was activated with glucose calcium and thrombin. Growth factors levels in PRP activated supernatant (PRP-AS) and wound healing ability of platelet gel (PG) in the full-thickness skin defect diabetic mouse model were compared.Results: We found the level of growth factors in PRP-AS derived from two groups of diabetic patients were not statistically different, whereas both lower than that from healthy volunteers. Similarly, we found better wound healing ability of PG from healthy volunteers than those from diabetic patients, but no difference between the two groups of diabetic patients in the mouse model.Discussion: Aspirin does not interfere with autologous PRP therapy when using calcium gluconate and thrombin as agonists. However considering the content of growth factors, PRP from healthy volunteers is a preferable option for promoting DFU repair.

Acetylsalicylic acid dosed at bedtime vs. dosed in the morning for circadian rhythm of blood pressure- a systematic review and meta-analysis.

Cardiovascular disease (CVD) is a leading global cause of morbidity and mortality, with high systolic blood pressure (SBP) identified as a major risk factor. Aspirin (Acetylsalicylic acid-ASA) has been considered for CVD prevention, prompting questions about its optimal use in primary and secondary prevention and the ideal dosing time to maximize its impact on circadian blood pressure rhythms. Previous research suggests a potential benefit of bedtime aspirin dosing in reducing blood pressure, attributed to its effects on the renin-angiotensin-aldosterone system and nitric oxide production. This systematic review and meta-analysis aim to further explore the circadian effects of aspirin on blood pressure, focusing on the timing of administration. Adhering to PRISMA guidelines, a comprehensive search of PubMed, Cochrane Library, and clinicaltrials.gov was conducted. Randomized controlled trials (RCTs) involving patients aged >18 with cardiovascular history and hypertension were included. The primary objective was to assess the impact of bedtime-dosed and morning-dosed aspirin on systolic and diastolic blood pressure. Low-dose aspirin was administered for primary or secondary prevention. The Cochrane Risk of Bias tool evaluated study quality. Meta-analyses were conducted using RevMan 5.3, with mean deviations and 95% confidence intervals employed for outcomes. Initial searches yielded 1,181 articles, with six studies meeting the inclusion criteria. These RCTs involved 1,470 patients, with 1,086 completing follow-up. Bedtime aspirin dosing demonstrated a significant reduction in both systolic and diastolic blood pressure compared to morning dosing (p < 0.05). Meta-analysis results for systolic blood pressure revealed a weighted mean difference of approximately 3.65 mmHg in favour of bedtime dosing, with low heterogeneity (I 2 = 0%). For diastolic blood pressure, the weighted mean difference was 1.92, again favouring bedtime dosing, with 3% heterogeneity. This meta-analysis, involving over 1,300 cardiovascular/hypertensive patients, supports the effectiveness of bedtime aspirin in reducing systolic and diastolic blood pressure compared to morning dosing. The results align with previous findings but distinguish themselves by incorporating a more diverse patient population and addressing moderate heterogeneity. While the study's outcomes are promising, further research, including larger sample sizes and longer durations, is warranted for comprehensive clinical implementation. As the study exclusively focused on aspirin timing, future investigations should explore sustained blood pressure effects in patients with clinical indications for aspirin alongside other hypertensive medications.

Pharmacological Thromboprophylaxis Effectiveness in Low-Risk Patients Undergoing Arthroscopic Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial

Background: There is a paucity of evidence and controversies regarding prophylaxis strategies in low-risk patients undergoing knee arthroscopy. This study aims to evaluate the effectiveness and safety of aspirin and low-molecular-weight heparin (LMWH) in an arthroscopic anterior cruciate ligament (ACL) reconstruction for low-risk patients. Methods: We performed a preoperational evaluation a week before surgery for any sign of pulmonary embolism (PE) and deep vein thrombosis (DVT). For this purpose, we used single limited compression Doppler ultrasonography (CUS) of the lower extremities. Rehabilitation started before the time of the surgery to improve the range of motion (ROM) and quadriceps muscle function. A team of 3 orthopedists performed the procedures. The same surgical technique and graft were used with spinal anesthesia, and operation time was recorded. Results: The mean age of participants was 31.4 ± 5.6 years, with 93 individuals (67%) being men and 23% women. No cases of DVT or PE were observed. Three cases in the LMWH group and one case in the aspirin group experienced minor surgical site bleeding. One case of hemarthrosis with normal ultrasonography occurred in the LMWH group. Regarding safety and effectiveness, there was no statistically significant difference between the parallel arms. Conclusion: The use of LMWH or aspirin after simple arthroscopic ACL reconstruction in low-risk patients showed no difference in effectiveness. Hence, the routine use of thromboprophylaxis in this setting is questionable although adverse events are rare

Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets.

Multi-omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi-step progression of BRDC, such as tumor protein P53 (TP53) mutation-associated estrogen receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification-associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS_Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T-cell lymphoma invasion and metastasis 1, androgen receptor, and aldo-keto reductase family 1 member C1 (TIAM1-AR-AKR1C1) axis promotes cell invasion and migration in DCIS_adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi-omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.

Aspirin enhances radio/chemo-therapy sensitivity in C. elegans by inducing germ cell apoptosis and suppresses RAS overactivated tumorigenesis via mtROS-mediated DNA damage and MAPK pathway

Previous studies have demonstrated that combination therapy involving radiotherapy and aspirin decreases the survival rate of cancer cells. However, the mechanism by which aspirin exerts its radiation sensitization effect at the in vivo level remains largely unclear. In this study, we employed Caenorhabditis elegans (C. elegans) as a model organism to investigate the effect of aspirin combined with radio/chemo-therapy on tumors at the individual level. Here, we illustrate that high-dose aspirin increases the expression of genes involved in core apoptosis pathways (egl-1, ced-9, ced-4 and ced-3) and induces germ cell apoptosis in C. elegans through mitochondrial outer membrane permeabilization (MOMP) and elevation of reactive oxygen species (ROS) levels. Crucially, aspirin-induces ROS upregulates the expression of genes critical for DNA damage response (hus-1, clk-2 and cep-1) and genes involved in MAPK pathways (lin-45, mek-2, mpk-1, sek-1 and pmk-1), thereby mediating the enhanced sensitivity of radio/chemo-therapy by aspirin. Notably, aspirin fails to induce germ cell apoptosis and enhance radio/chemo-therapy in C. elegans lacking the expression of each of those genes. Furthermore, in a C. elegans tumor-like symptom model, aspirin enhances radio/chemo-therapy sensitivity through ROS induction. However, low-dose aspirin can diminish the apoptotic signal of reproductive cells in C. elegans and exert anti-inflammatory effects. Our research results suggest that the tumor-suppressive and radio/chemo-therapy sensitizing effects of aspirin provide robust experimental evidence for improving the clinical efficacy of tumor radio/chemo-therapy and deepening our understanding of aspirin's mechanism of action in cancer.

Protective effect of aspirin and gentisic acid, a plant-derived phenolic acid, on acrylamide-induced neurotoxicity by inhibiting apoptosis and autophagy.

Acrylamide (ACR) is a toxic agent for humans and animals. Gentisic acid, anaspirinmetabolite, has antioxidant activity. Therefore, the present study investigated the probable protective effects of aspirin and gentisic acid on ACR-induced neurotoxicity in PC12 cells and rats. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the effects of aspirin and gentisic acid (1.25, 2.5, 5 µM) on ACR (5 mM) toxicity. Male Wistar rats were randomly divided into 13 groups: (1) Control group, (2) ACR (50 mg/kg, 11 days, i.p.), (3-5) ACR + aspirin (25, 50, 75 mg/kg, 11 days, p.o.), (6-8) ACR + gentisic acid (25, 50, 75 mg/kg, 11 days, p.o.), (9) ACR + vitamin E (200 mg/kg, every other day, i.p.), (10, 11) Aspirin (75, 100 mg/kg, 11 days, p.o.), (12, 13) Gentisic acid (75, 100 mg/kg, 11 days, p.o.). Behavioral tests were assessed on the final day of the study. In the cerebral cortex, malondialdehyde (MDA), glutathione (GSH), cleaved-caspase-3, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein levels were evaluated. When compared with the ACR group, aspirin (2.5, 5 µM) and gentisic acid (2.5 µM) significantly enhanced cell viability. In comparison to the control group, ACR induced severe motor impairment, elevated MDA, cleaved-caspase-3, LC3 II/I ratio, and decreased GSH levels in the cerebral cortex of rats. ACR-induced changes were significantly reversed by aspirin and gentisic acid (25 mg/kg). Oxidative stress, apoptosis, and autophagy play important roles in the neurotoxicity of ACR. Aspirin and gentisic acid significantly reduced ACR-induced toxicity by inhibiting the mentioned mechanisms.

Impact of Dipyrone Administration on Postoperative Analgesia and Aspirin Effect in Patients Undergoing Coronary Artery Bypass Grafting: The Prospective Randomized DipASA Study

ObjectiveThe aim of the study was to investigate the impact of dipyrone administration on postoperative analgesia and acetylsalicylic acid (ASA) effect in patients undergoing coronary artery bypass grafting (CABG). DesignA prospective randomized study. SettingSingle-university hospital setting. ParticipantsNinety-eight patients who underwent CABG between April 2022 and May 2023. InterventionsASA effect were measured at six time points with impedance aggregometry (Multiplate) and thromboelastography (TEG6sPlateletMapping). Patients were randomized to one of three groups: intravenous ASA and dipyrone at the same time (group 1), intravenous ASA and dipyrone with a 2-hour delay (group 2), and intravenous ASA alone (group 3). Postoperative analgesic effects (numeric rating scale, NRS) and the prevalence of potential ASA non-response (defined as ASPI>40U and TEG-ASA-inhibition<50%) were recorded. Measurements and Main Results80 of 90 analyzed patients took ASA preoperatively. All patients received intravenous ASA 100mg from postoperative day 1. The effect of ASA did not significantly differ between the study groups at any time for either platelet function test. NRS values did not differ between the study groups at any time (p=0.469). Patients in group 3 received significantly more additional co-analgesics than patients who received dipyrone (p=0.005). ASA non-response was detected in 38.9% and 67.8% on 7th postoperative day, respectively. ConclusionsDipyrone given after CABG seems to be safe and did not show any significant effect on platelet inhibition after ASA administration. Patients taking dipyrone postoperatively need significantly less additional co-analgesics. The ASA effect on platelet function should be checked at least once after surgery.

Aspirin reduces Ponatinib-induced cardiovascular toxic phenotypes and death in zebrafish

BackgroundPonatinib (Iclusig) is an oral tyrosine kinase BCR-ABL inhibitor for treating patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) who are resistant to the therapies with other tyrosine kinase inhibitors. However, adverse cardiovascular events caused by Ponatinib are a serious issue that affects patients' survival rates. Thus, it is necessary to search for candidate drugs to reduce the cardiovascular toxicity of Ponatinib. PurposeTo investigate the effects of Aspirin on Ponatinib-induced cardiovascular toxicity in zebrafish. MethodsAB strain of wild type zebrafish (Danio rerio), Tg (cmlc2: GFP) transgenic zebrafish, and Tg (gata1: dsRed) transgenic zebrafish were used as in vivo models to assess survival, blood flow, cardiac morphology, and function. Thrombus formation was detected using O-dianisidine staining. The transcriptome of zebrafish larvae treated with Ponatinib was assessed using RNA sequencing. ResultsPonatinib not only reduced survival rate but also caused cardiovascular toxic events such as pericardial edema, abnormal heart structure, low heart rate, and thrombosis. In addition, whole-body transcriptome analysis showed that Ponatinib up-regulated the expression of cyclooxygenase-1 (COX-1). Compared with other antithrombotic drugs, a COX-1 inhibitor Aspirin more effectively reduced ponatinib-induced cardiovascular toxicity events and improved the survival rate of zebrafish larvae. ConclusionOur findings suggest that Aspirin exhibits the potential to reduce Ponatinib-induced cardiovascular toxicity.

S2001 Effect of Aspirin and Statin on Liver Markers and Mortality in Patients With Cirrhosis

S2001 Effect of Aspirin and Statin on Liver Markers and Mortality in Patients With Cirrhosis

Long-Term Effects of Low-Dose Aspirin on Gastrointestinal Symptoms and Bleeding Complications in Patients with Type 2 Diabetes.

Low-dose aspirin for primary prevention is determined by the balance of risks of cardiovascular events and adverse effects. We assessed the long-term gastrointestinal symptoms or bleeding with low-dose aspirin in diabetic patients. The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized clinical trial to evaluate the efficacy and safety of low-dose aspirin in patients with type 2 diabetes. As a posthoc analysis, we investigated the incidence of upper gastrointestinal symptoms or bleeding in aspirin (100 mg enteric-coated aspirin or 81 mg buffered aspirin daily) and no-aspirin groups within and beyond 3 years. Of 2535 patients (mean age 65 years, 55% male) followed for a median of 11.2 years, 1258 were included in the aspirin group (951 enteric-coated, 208 buffered, 99 unknown) and 1277 were included in the no-aspirin group. The cumulative incidence of upper gastrointestinal symptoms or bleeding was higher in the aspirin group than the no-aspirin group (8.8% vs. 5.7% at 18 years; p<0.0001). The increased risk in the aspirin group was prominent within 3 years, and thehazard ratio (HR) [95% confidence interval (CI)] of the aspirin group was 7.10 [3.21-15.7], but attenuated beyond 3years (HR 1.20 [0.76-1.89]). In 1159 patients in the aspirin group, the cumulative incidence was lower in the enteric-coated than in the buffered aspirin groups (2.9% vs. 7.3%; p=0.003) within 3 years, and the adjusted HR of enteric-coated aspirin was 0.38 [0.20-0.72] compared with the buffered aspirin group. The upper gastrointestinal symptoms or bleeding of low-dose aspirin within 3 years, and the aspirin formulations, were relevant for decision making of initiation and continuation of low-dose aspirin for primary prevention.

Aspirin increases estrogen levels in the placenta to prevent preeclampsia by regulating placental metabolism and transport function

Preeclampsia is a unique multisystem progressive disease during pregnancy, which seriously endangers the health of pregnant women and fetuses. In clinical practice, aspirin is recommended for the prevention of preeclampsia, but the mechanism by which aspirin prevents preeclampsia has not yet been revealed. This report comprehensively evaluates the effects of aspirin on the expression and activity of placental metabolic enzymes and transporters. We found that after aspirin administration, only the expression of organic anion transporter 4 (OAT4) in the placenta showed a significant increase at both mRNA and protein levels, consistent with the results in JAR cells. Meanwhile, studies on the metabolic enzyme activity in the placenta showed a high upregulation of CYP19A1 activity. Subsequently, significant increases in endogenous substrates of OAT4 and CYP19A1 (dehydroepiandrosterone sulfate (DHEAS) and androstenedione) as well as estrone were detected in placental tissue. In summary, aspirin enhances the transport of DHEAS through OAT4 and promotes the metabolism of androstenedione through CYP19A1, thereby increasing estrogen levels in the placenta. This may be the mechanism by which aspirin prevents preeclampsia and maintains pregnancy by regulating the metabolism and transport function of the placenta.

Cardiovascular disease and stroke following cancer and cancer treatment in older adults

AbstractBackgroundCancer survivors can be at risk of cardiovascular disease (CVD) because of either their malignancy or its treatment. Although studies linking cancer and CVD exist, few examine risk in older adults, the impact of cancer treatment, or the effect of aspirin on reducing risk in this cohort.MethodsThe authors conducted a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial to investigate the impact of cancer and cancer treatment on a composite CVD end point comprising hospitalization for heart failure (HHF), myocardial infarction (MI), and stroke.ResultsOf 15,454 Australian and US ASPREE participants, 1392 had an incident cancer diagnosis. Rates of CVD were greater in the cancer risk‐set compared to the cancer‐free risk‐set (20.8 vs. 10.3 events per 1000 person‐years; incidence rate ratio, 2.03; 95% confidence interval, 1.51–2.66), with increased incidence seen across MI, HHF, overall stroke, and ischemic stroke. Increased incidence remained after adjustment for clinically significant risk factors for CVD. Incidence was greatest in metastatic, hematological, and lung cancer. Chemotherapy was associated with increased risk of CVD. Similar rates of CVD were seen across aspirin and placebo groups.ConclusionsIncidence of CVD, including MI, HHF, and ischemic stroke, was increased in older adults with cancer. Aspirin did not impact CVD incidence. Risk may be higher in those with metastatic, hematological, and lung cancer, and following chemotherapy.

Exploring Aspirin's Potential in Cancer Prevention: A Comprehensive Review of the Current Evidence.

Aspirin, traditionally recognized for its analgesic, anti-inflammatory, antipyretic, and antiplatelet effects, has recently attracted attention for its potential role in cancer prevention. Initially studied for cardiovascular disease prevention, emerging evidence suggests that aspirin may reduce the risk of certain cancers, particularly colorectal cancer (CRC). This narrative review integrates findings from early studies, animal models, epidemiological data, and clinical trials to evaluate aspirin's efficacy as a chemopreventive agent. Aspirin's anticancer effects are primarily attributed to its cyclooxygenase (COX) enzyme inhibition, which decreases prostaglandin E2 (PGE2) levels and disrupts cancer-related signaling pathways. While epidemiological studies support an association between aspirin use and reduced cancer incidence and mortality, especially for CRC and potentially for breast (BC) and prostate cancers (PCa), the risk of adverse effects, such as gastrointestinal (GI) and intracranial bleeding, complicates its use and warrants careful consideration. The decision to use aspirin for cancer prevention should be individualized, balancing its therapeutic benefits against potential adverse effects. It also underscores the necessity for further research to refine dosage guidelines, assess long-term impacts, and explore additional biomarkers to guide personalized cancer prevention strategies.