MIS-C Like Features in a Patient of Atypical Kawasaki Disease: A Case Report.

ABSTRACT: Kawasaki Disease is multisystem vasculitis affecting young children and infants. While the diagnosis of a typical form of Kawasaki Disease is obvious, there are some patients who do not fulfill the classic diagnostic criteria for the disease which is termed as 'incomplete Kawasaki Disease' or 'Atypical Kawasaki Disease'. We present a case of a 6 months old child with fever who after failing to respond to IV antibiotics showed considerable improvement after administering aspirin and Intravenous Immunoglobulin thus diagnosed as Atypical Kawasaki Disease. Moreover, due to sharing of similar features by both Kawasaki Disease and Multiple Inflammatory Syndrome in Children, the case posed a diagnostic dilemma.

ADVERSE EVENTS in PATIENTS with CARDIOVASCULAR DISEASE TAKING PROTON PUMP INHIBITORS.

INTRODUCTION: Proton pump inhibitors (PPIs) rank among the most frequently prescribed medications to treat acid-related diseases. Mounting concerns surround the potential for serious adverse events, including cardiovascular events, associated with their prolonged use/misuse. AREAS COVERED: This comprehensive review explores cardiovascular adverse events linked to PPI use among high-risk cardiovascular patients. A structured search was conducted on PubMed. EXPERT OPINION: Many patients with cardiovascular disease who require antiplatelet treatment will require long-term PPI treatment. Interpreting the published data is not straightforward. First, because there is no plausible mechanistic explanation for PPIs to induce cardiovascular events apart from the potential interaction with the metabolism of thienopyridines. Although several observational studies have shown an increased cardiovascular risk and mortality in patients taking long-term PPIs, most available clinical trials and meta-analyses of available studies do not. However, the absence of firm evidence of this link does not necessarily imply that this association does not exist, and other hypothesis must be explored. Anemia is a common event in patients who take antiplatelet therapy and PPIs, and it is a factor associated with cardiovascular events and death. Anemia in these patients is often attributed to erosive lesions of the small intestine, where PPI may play a key role by modifying the microbiota.

How can we reduce maternal mortality due to preeclampsia? The 4P rule.

In low and middle-income countries such as Brazil, most maternal deaths are related to hypertensive complications. Preeclampsia is the leading cause of maternal mortality and morbidity. Significant proportion is associated with the following factors: lack of identification of high-risk women, lack of adequate prevention, difficulty in maintaining a high-risk prenatal follow-up, delayed diagnosis, insecurity and low use of magnesium sulphate, delayed pregnancy interruption and lack of postpartum follow-up of these high-risk cases. Four major actions are proposed to minimize this alarming clinical picture and reduce the mortality rates due to preeclampsia, called the "4 P Rule" (Adequate Prevention - Vigilant Prenatal Care - Timely Delivery (Parturition) - Safe Postpartum). From this simple "rule" we can open a range of important processes and reminders that may help in the guidance of preeclampsia management.

Highly specific screening of aspirin resistance-related single-nucleotide polymorphisms using ligase chain reaction strategy.

Aspirin (ASP) is currently the drug of choice for antiplatelet therapy. However, approximately 5%-45 % of patients are resistant to ASP and do not achieve the expected result. At present, a few studies have investigated the correlation between ASP resistance (AR) and single-nucleotide polymorphism (SNP). Traditional detection methods are time-consuming and laborious, affecting the accuracy of personalized medicine. This study aimed to establish a new assay to identify four SNPs associated with AR. A large amount of double-stranded DNA was formed after multiple cycles of specific exponential amplification by ligase chain reaction, the specific melting peak of which was visible in the detection curve, with a detection limit of 10-11mol/L. The specificity experiments of different proportions of wild-type and mutant plasmid standards showed that the novel method could detect up to 1 % allele frequency and the specificity was good. Clinical blood samples of 57 patients were tested in this study. The results were consistent with those of sequencing and more accurate and reliable than those of the high-resolution melting method. The technique used in this study was simple, sensitive and specific compared with the traditional method. Statistical analysis revealed that AR was significantly correlated with the rs12041331 site of the PEAR1 gene and the rs1695 site of the GSTP1 gene, providing an important reference value for the study of AR.

Higher-Than-Usual Target International Normalized Ratio (INR) Range Required With On-X Aortic Valve Secondary to Recurrent Thromboembolic Strokes: A Case Report.

Although the On-X aortic valve (AO) is considered less thrombogenic compared to its counterparts, we present a case where recurrent thromboembolic ischemic stroke occurred, first with a slightly sub-therapeutic, then even with an elevated International Normalized Ratio (INR).  A 36-year-old male, the background of On-X AO replacement but no other risk factors, developed thromboembolic stroke twice while on Warfarin, first with INR 1.4, second with INR 2.4. Despite extensive investigation, other than elevated levels of low-density lipoproteins, no other treatable cause was found with the latter episode. The INR range was increased to 2.5-3.5, and aspirin and statin were added. The occurrence of thromboembolic stroke with an On-X AO despite maintaining an INR of 2.4, presents a dilemma for future prevention. The American Heart Association (AHA) and the American College of Cardiology (ACC) guidelines for thromboembolism prevention in case of an On-X AO recommend an INR range of 1.5-2 as being effective when warfarin is used along with aspirin. The take-home message is that the recommendation of an INR range of 1.5-2 with an On-X AO should be approached with caution; aspirin should be strongly considered regardless of the presence of thromboembolic risk factors. Patients developing thromboembolism have a high risk of recurrence. Therefore, a higher INR, along with the addition of aspirin and statin should be considered. Studies are needed to establish guidelines for a reliable INR range in these scenarios.

Predictive modeling of medication adherence in post myocardial infarction patients: a bayesian approach using beta-regression.

AIMS: Predicting medication adherence in post myocardial infarction (MI) patients has the potential to improve patient outcomes. Most adherence prediction models dichotomize adherence metrics and status. This study aims to develop medication adherence prediction models that avoid dichotomizing adherence metrics and to test whether a simplified model including only 90-days adherence data would perform similarly to a full multivariable model. METHODS: Post MI adult patients were followed for 1-year post the event. Data from pharmacy records were used to calculate proportion of days covered (PDC). We used Bayesian beta-regression to model PDC as a proportion, avoiding dichotomization. For each medication group, statins, P2Y12 inhibitors and aspirin, two prediction models were developed, a full and a simplified model. RESULTS: 3692 patients were included for model development. The median (Inter quartile range) PDC at 1-year for statins, P2Y12 inhibitors and aspirin was 0.8 (0.33, 1.00), 0.79 (0.23, 0.99) and 0.79 (0.23, 0.99), respectively. All models showed good fit to the data by visual predictive checks. Bayesian R2 for statins, P2Y12 inhibitors and aspirin models were 61.4%,71.2% and 55.2%, respectively. The simplified models showed similar performance compared with full complex models as evaluated by cross validation. CONCLUSIONS: We developed Bayesian multilevel models for statins, P2Y12 inhibitors and aspirin in post MI patients that handled 1-year PDC as a proportion using the beta-distribution. In addition, simplified models, with 90-days adherence as single predictor, had similar performance compared with full complex models.

Evaluating the safety and efficacy of medical management in extracranial pseudoaneurysms: a comparative study.

OBJECTIVE: As endovascular interventions become safer and their use more prevalent for treating extracranial pseudoaneurysms, fewer pseudoaneurysms are treated with medical therapy alone. This study aimed to assess the indications for intervention and the safety of medical management. METHODS: A dual-center retrospective analysis was conducted on patients diagnosed with extracranial carotid and vertebral pseudoaneurysms between December 2006 and June 2023. RESULTS: Of 145 pseudoaneurysms, 121 (83%) received medical therapy, 22 (15%) were treated endovascularly, and 2 (1.4%) were treated with open surgery. In the medical group, there were 2 (1.9%) complications, one unrelated to the pseudoaneurysm. In the intervention group, there were 3 (16%) complications, with 1 patient requiring two retreatments and sacrifice of the vessel. Major trauma (OR 4.0, 95% CI 1.3-14; p = 0.02), use of digital subtraction angiography as the initial imaging modality (OR 9.8, 95% CI 2.5-42; p < 0.01), and a maximum lesion diameter > 6 mm (OR 5.3, 95% CI 1.4-25; p = 0.03) proved to be significant in the decision to intervene. At a median follow-up of 18.1 months, 94.7% of the lesions treated with intervention healed completely compared with 19% of aneurysms in the medical group. Among those medically managed that did not resolve, the median change in diameter was -0.4 mm (IQR -1.8 to 0.4 mm). Age ≤ 50 years and aneurysm maximum diameter ≤ 6 mm predicted healing at follow-up in the medical group with 92% specificity and 65% sensitivity (area under the curve 0.87). At follow-up, 98% of patients were functionally independent (modified Rankin Scale score ≤ 2). CONCLUSIONS: Medical management alone is safe for most extracranial pseudoaneurysms, resulting in significantly fewer complications than endovascular intervention. Maximum diameter ≤ 6 mm and age ≤ 50 years were significant predictors of pseudoaneurysm resolution with medical therapy alone. Lesions that do not heal do not cause further symptoms or require additional intervention.

125 Years of Aspirin: Status of Analytical Methods.

Aspirin, an analgesic, antipyretic and non-steroidal anti-inflammatory drug, was a fascinating discovery that became the precursor to one of the oldest pharmaceutical success stories. It was discovered in 1899 by Felix Hoffman and patented in 1900. In 2024, Aspirin turns 125 years old and is still one of the bestselling medicines today. This review aims to celebrate 125 years of Aspirin and show the status of analytical methods available in the literature to evaluate pharmaceutical products based on Acetylsalicylic Acid (ASA). In addition, it contextualizes them with the current needs of green and clean analytical chemistry. ASA, despite being consolidated in the consumer market, embraces continuous improvement as it is a fundamental part of studies for other new purposes and studies with associations with other active ingredients. In the manuscripts available in the literature, ASA is predominantly evaluated by HPLC (41%) and UV-Vis (41%) methods, which use methanol (21.82%) and acetonitrile (18.18%), followed by buffer (16.36%). The most evaluated pharmaceutical matrix is ASA tablets (40%), followed by ASA tablets in combination with other drugs (26%). While ASA continues to innovate in the market through new forms of delivery and combinations, as well as intended purposes, the analytical methods for evaluating its pharmaceutical products do not. They continue with non-eco-efficient analytical options, which can significantly improve and meet the current demand for green and sustainable analytical chemistry.

Aspirin Hypersensitivity in Patients with Coronary Artery Disease: An Updated Review and Practical Recommendations.

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity.

The association between low-dose aspirin intake and osteoarthritis: a population-based cross-sectional study based on NHANES.

Objectives: Low-dose aspirin is widely used as a preventive medication for cardiovascular diseases. However, there is controversy regarding the impact of low-dose aspirin on articular cartilage. The aim of this study is to explore the association between low-dose aspirin intake and osteoarthritis (OA). Methods: We conducted a cross-sectional study based on the United States population data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. The investigation of low-dose aspirin intake and the diagnosis of OA was based on self-reporting in questionnaires. Multivariate regression models was used to assess the relationship between low-dose aspirin intake and OA. In addition, subgroup and interaction analysis were performed to assess the robustness of the results. Results: A total of 12,215 participants were included in this study. Multivariate logistic regression analysis showed that low-dose aspirin use had significantly increased the odds of OA (OR = 1.14; 95% CI: 1.01-1.28; p = 0.035). A significant and consistent association of low-dose aspirin intake with OA was still observed in each subgroup stratified by gender, age, and the presence of comorbidities including diabetes, coronary heart disease, hypertension, and stroke. The results illustrated that the relationship between low-dose aspirin intake and OA was stable in all subgroups and had no interaction. Conclusion: Our study confirmed that low-dose aspirin intake may increase the risk of OA. Attention should be paid to the possibility of joint degenerative changes in patients who take low-dose aspirin chronically. However, further studies are needed to explore the possible mechanisms behind this association.

Cervical Spinal Epidural Hematoma After Spinal Anesthesia for Cesarean Section in the Parturient Using Long-Term Low Dose Aspirin.

Spinal epidural hematoma (SEDH) is a rare but serious complication associated with spinal anesthesia (SA). We present an unusual case of cervical SEDH occurring 24 h after a lumbar puncture for a cesarean section. The patient, who was on low-dose aspirin due to preeclampsia, initially exhibited neurological symptoms resembling a stroke. Despite a normal magnetic resonance imaging (MRI) of the brain, further investigations revealed a SEDH located between the C3 and T1 segments, well beyond the L3-L4 puncture site. Although coagulation tests were normal, this case underscores the potential risk of low-dose aspirin in affecting platelet function, which may contribute to SEDH development. It also emphasizes the importance of considering spinal MRI when neurological symptoms arise after SA, even if initial cranial MRI results are normal. She underwent emergency C3-T1 laminectomy through a dorsal midline approach. Her motor, sensory, and sphincter functions fully recovered at follow-up.

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.

Aspirin Hypersensitivity in Patients With Atherosclerotic Cardiovascular Disease.

Low-dose aspirin remains the most commonly used antiplatelet agent among patients with atherosclerotic cardiovascular disease. Aspirin hypersensitivity occurs in 1% to 5% of patients and is among the most frequent causes for prohibiting the use of aspirin, posing a significant dilemma on how to manage these patients in clinical practice. Aspirin hypersensitivity is often misinterpreted and confused with aspirin intolerance, with treatment approaches being often unclear and lacking specific recommendations. Aspirin desensitization and low-dose aspirin challenge have emerged as pragmatic, effective, and safe approaches in patients with suspected or confirmed aspirin hypersensitivity who require aspirin therapy, but they are underused systematically in clinical practice. Furthermore, there is confusion over alternative antiplatelet agents to be used in these patients. The pathophysiological mechanisms and classification of aspirin hypersensitivity, as well as alternative strategies and practical algorithms to overcome the need for aspirin use in patients with atherosclerotic cardiovascular disease with suspected aspirin hypersensitivity, are discussed.

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.

Platelet-rich plasma (PRP), enriched with multiple growth factors, effectively promote the healing of refractory diabetic foot ulcer (DFU). We found that aspirin, as a commonly used antiplatelet drug for diabetic patients, did not affect the growth factors content in autologous PRP from diabetic patients or its wound-healing ability in diabetic mouse skin defects. However, PRP from healthy volunteers showed superior performance in both aspects. Our study provide a theoretical basis for personalized PRP treatment plans for DFU patients.

A randomised crossover design study comparing the pharmacokinetics and pharmacodynamics of two single Doses of ORal Aspirin (75 mg v 150mg) in pregnant women at risk of pre-eclampsia (DORA): implications on assessing aspirin response and patient adherence to therapy.

BACKGROUND: Pregnancy is associated with physiological changes that can alter the pharmacokinetic and pharmacodynamic profile of many drugs. Low-dose aspirin is used for pre-eclampsia (PE) prevention; however aspirin's pharmacokinetics and pharmacodynamics are poorly studied in pregnant women. OBJECTIVE: The aim of this study was to compare the pharmacodynamics of two common doses of aspirin (75 and 150 mg) used for PE prevention in high-risk women by examining their effect on thromboxane B2 (TbxB2) inhibition. A secondary objective sought to assess if salicylic acid could be used as means to evaluate adherence to aspirin. STUDY DESIGN: Fourteen pregnant women from a large maternity unit in England, eligible for prophylactic aspirin according to NICE guidance, were recruited into 2 x 2 randomised crossover trial. Blood samples were collected at baseline, 1, 2, 3, 4, 15, 16, 17, 18 and 19-hours post ingestion of either 75 or 150 mg of aspirin with a 7-day washout period. Plasma concentrations of salicylic acid (SA), the primary metabolite of aspirin, were determined using high performance liquid chromatography. Pharmacodynamic response to aspirin was assessed by measuring serum thromboxane B2 (TbxB2) concentrations by an enzyme-linked immunosorbent assay. Analyte data were compared using nonparametric test statistics for paired values (Wilcoxon Signed Rank Test) and areas under serum SA concentration versus time curve (AUC). Pharmacokinetic modelling was used to bridge the data arising from the overnight sampling break. The trial was registered with the ISRCTN (reg number ISRCTN14693054). RESULTS: A single dose of 150 mg of aspirin produced higher plasma exposure of SA in comparison to 75 mg (median SA AUC0-19 16.7 µg*h/ml (IQR 15.2-19.3) vs 6.8 µg*h/ml (IQR 6.1- 8.3), p<0.001). Pharmacokinetic models suggest that plasma SA concentrations could be detected above the maximum concentration recorded at baseline for the first 11 hours after 75 mg and for 12 hours after 150 mg aspirin dosing, providing a time frame to confirm recent aspirin ingestion. The 150 mg aspirin dose produced a greater normalised reduction in serum TbxB2 (median normalised reduction 95.7% (IQR 92.6%- 97.3%) than the 75 mg dose (median normalised reduction 84.6% (IQR 77.3-92.3%), p<0.007. CONCLUSION: Compared to the 75 mg dose, 150 mg of aspirin more effectively inhibits TbxB2, providing rationale for further investigation of effectiveness of higher doses for pre-eclampsia prevention. Despite limitations, measuring serum SA concentration could still be used in future models to test adherence if done within 11-12 hours after ingestion.

The Effect of Antiplatelet Therapy on COVID-19.

Platelets are one of the major targets of SARS-CoV-2. Activated platelets release prothrombotic substances, express adhesion molecules, and activate coagulation, thereby contributing to the thrombotic tendency in COVID-19. However, the antiplatelet therapy is not recommended in the current international guidelines. We think that the initiation timing and the target severity are the causes of the failure in clinical trials. As shown in the clinical studies that examined the effects of anticoagulants, early initiation in moderate severity is necessary for the success of antithrombotic therapy. Future trials are warranted to study the effects of antiplatelets in such conditions.

Impact of prior aspirin use on left ventricular function in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: An echocardiographic evaluation.

Introduction: Previous studies have investigated the potential influence of prior aspirin use on cardiac function in patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PPCI). However, the results from these studies have been conflicting. This study aimed to investigate whether prior aspirin use affects left ventricular (LV) function in these patients using echocardiography. Methods: The study included 260 consecutive STEMI patients, who were divided into two groups based on the presence or absence of prior aspirin use. Echocardiographic parameters, such as maximal left atrial (LA) size, LV ejection fraction (LVEF), early diastolic velocity (e'), E/A ratio, and E/e' ratio, were assessed within 72 hours of admission. Results: Aspirin users had an older age compared to non-users, as well as lower body mass index and renal function. They also had a greater history of hypertension and were more likely to be taking statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and calcium channel blockers. There were no significant differences in LVEF, maximal LA size, E/A ratio, E/e' ratio, and deceleration time between aspirin users and non-users. e' wave was marginally lower in aspirin users (P=0.054). After controlling for confounding variables, the previous use of aspirin did not show a significant impact. Conclusion: Prior aspirin use in STEMI patients does not have a significant impact on LV echocardiographic parameters. Our conclusions remained consistent even after adjusting for potential confounders.

Predicting laboratory aspirin resistance in Chinese stroke patients using machine learning models by GP1BA polymorphism.

This study aims to use machine learning model to predict laboratory aspirin resistance (AR) in Chinese stroke patients by incorporating patient characteristics and single nucleotide polymorphisms of GP1BA and LTC4S. 2405 patients were analyzed to measure the Mutation frequency of GP1BA rs6065 and LTC4S rs730012. 112 patients with first-stroke arteriostenosis were prospectively enrolled to establish machine learning model. GP1BA rs6065 mutation frequency is 5.26% and LTC4S rs730012 is 14.78%. GP1BA rs6065 CT patients have more sensitivity to aspirin than CC genotype. Simple linear regression identified significant associations with age, smoking, HDL and GP1BA rs6065. Random forest (RF) and extreme gradient boosting (XGBoost) demonstrated predictive capabilities for AR. Findings suggest pre-identifying GP1BA rs6065 could optimize aspirin treatment, enabling personalized care and future research avenues.

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Polygenic risk, aspirin and primary prevention of coronary artery disease.

AIMS: Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease versus the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk. METHODS AND RESULTS: We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12,031 genotyped participants (5,974 aspirin, 6,057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin versus placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk (adjusted Hazard Ratio [aHR]=1.30 [1.06-1.61], P=0.01) but no significant CAD reduction (aHR=0.84 [0.64-1.09], P=0.19). However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin (aHR=0.53 [0.31-0.90], P=0.02) without increased bleeding risk (aHR=1.05 [0.60-1.82], P=0.88). Interaction between the GPSMult and aspirin was significant for CAD (q5 versus q1, P=0.02) but not bleeding (P=0.80). CONCLUSION: The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition.