Obstetric care provider's knowledge about the use of low dose aspirin for preeclampsia prevention in low and middle income countries: a systematic review and meta-analysis.

INTRODUCTION: Preeclampsia can elevate the likelihood of unfavorable consequences for a mother, such as severe morbidity and mortality. World Health Organization recommends low dose acetylsalicylic acid (aspirin, 75 mg per day) for the prevention of preeclampsia in women at moderate or high risk of developing the condition. The use of low dose aspirin is dependent on the knowledge of health care providers working in the antenatal care units. We found inconsistent figures regarding the knowledge level of health care providers on low dose aspirin for preeclampsia prevention around different low and middle income countries in the world. Thus, determining the pooled knowledge level of health care providers is very important. METHODS: This systematic review and meta-analysis (SRMA) was conducted on the knowledge level of among obstetric care providers towards preeclampsia prevention in low and middle income countries. We identified relevant literature in the English language only. A comprehensive search was conducted on databases such as PubMed, Google Scholar, HINARI, and Scopus. Subsequently, all datasets were exported to Mendeley reference manager and transferred to a Microsoft Excel spreadsheet to eliminate duplicate data during the review process. The extracted Microsoft Excel spreadsheet format data was imported to STATA software version 17 (STATA corporation, Texas, USA) for analysis. Then random effect model was used to estimate the pooled level of knowledge of health care providers on low dose aspirin for preeclampsia prevention in low income countries. Cochrane Q-test and I2 statistics were computed to assess heterogeneity among all the studies included in this SRMA. RESULT: A total of 1231 articles were identified through our search strategies, including Google Scholar, PubMed, Hinari and Scopus. Ultimately, six articles met the eligibility criteria for inclusion in the final SRMA. The pooled knowledge level of healthcare providers regarding the use of low-dose aspirin for preeclampsia prevention in low-income countries was found to be 16.38% (95% CI: 4.36-28.40). The Cochrane heterogeneity index, with a substantial I2 value of 98.89% and a significant P-value of 0.01, indicated significant heterogeneity among the primary studies included. CONCLUSION: the knowledge level of obstetric care providers in low and middle income countries is found very low and all the governmental and non-governmental organizations should strive to enhance the knowledge of obstetric care providers on the use of low dose aspirin for preeclampsia prevention in low and middle income countries.

Endometriosis and aspirin: a systematic review.

Introduction: Endometriosis is delineated as a benign yet steroid-dependent disorder characterized by the ectopic presence of endometrial glandular and stromal cells outside the uterine cavity, affecting estimated 10%-15% of women of reproductive age, 20%-50% of all women with infertility and costing a great economic burden per-patient. Endometriosis exerts pervasive influence on multiple facets of female reproductive physiology. Given its characterization as a chronic inflammatory disorder, escalated levels of pro-inflammatory cytokines were unequivocally recognized as well-established characteristics of endometriosis, which might attribute to mechanisms like retrograde menstruation, progesterone receptor resistance, and immune dysregulation. Therapeutic utilization of non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, analgesic agent for reducing pain, inflammation, and fever, could be holding promise in augmenting reproductive outcomes of endometriosis women. Therefore, the objective of this comprehensive review is to elucidate the intricate interplay between endometriosis and aspirin, both within the context of infertility and beyond. We meticulously explore potential pharmacological agents targeting endometriosis, which may concurrently optimize the efficacy of reproductive interventions, while also delving into the underlying mechanistic pathways linking endometriosis with inflammatory processes. Methods: We conducted a comprehensive search in the data available in PubMed and the Web of Science using the terms 'endometriosis' and 'aspirin'. Then analyzed the identified articles based on established inclusion and exclusion criteria independently by three reviewers. Results: The survey of the chosen terms revealed 72 articles, only 10 of which were considered for review. Discussion: Based on the research available currently, it is not substantial enough to address the conclusion that aspirin shall be an effective therapeutic choice for endometriosis, further studies are needed to elucidate the efficacy, safety profile, and optimal dosing regimens of aspirin in the context of endometriosis treatment.

Effectiveness of low-dose rivaroxaban in preventing recurrent major adverse cardiovascular events in coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Despite advancements in coronary artery disease (CAD) management, major adverse cardiovascular events persist. Vitamin K antagonists and direct oral anticoagulants present bleeding risks. Low-dose rivaroxaban (2.5 mg) is approved by the European Society of Cardiology and the US Food and Drug Administration for CAD. The survival advantage and risk-benefit profile of combining low-dose rivaroxaban with aspirin for CAD patients remain uncertain. This meta-analysis aims to compare the efficacy of low-dose rivaroxaban plus aspirin versus aspirin monotherapy in CAD patients. METHODS: We systematically searched databases for randomized controlled trials exploring low-dose rivaroxaban with aspirin in CAD patients. Of the 6220 studies screened, five met the inclusion criteria. Primary outcomes included myocardial infarction, stroke, major bleeding events, and all-cause mortality. The analysis employed a fixed-effects model, calculating hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Five randomized controlled trials involving 41,351 participants were included. Rivaroxaban (2.5 mg) significantly reduced all-cause mortality (HR, 0.88; 95% CI, 0.81-0.95; P = 0.002), myocardial infarction (HR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and stroke (HR, 0.61; 95% CI, 0.49-0.76; P < 0.00001) compared to aspirin alone. However, it increased major bleeding risk (HR, 1.66; 95% CI, 1.40-1.97; P < 0.01). Meta-regression revealed no dose-dependent impact on all-cause mortality. CONCLUSION: Low-dose rivaroxaban demonstrates survival benefits and reduces myocardial infarction and stroke risks in CAD patients, albeit with an increased risk of major bleeding. Consideration of patient bleeding risk is crucial when adding rivaroxaban to antiplatelet therapy. Further research is warranted to compare its effectiveness and safety with dual antiplatelet therapy or P2Y12 inhibitors.

Clinical efficacy and adverse effects of LMWH combined with ASA in the treatment of RSA: A meta-analysis and systematic review.

BACKGROUND: The incidence of recurrent spontaneous abortion (RSA) in the clinic shows an increasing trend year by year, and the coagulation status of this group of patients is mostly relatively abnormal. Currently, commonly used drugs in clinical practice include Aspirin (ASA) and low molecular weight heparin (LMWH), but their optimal treatment remains controversial. We aimed to evaluate the clinical efficacy and adverse effects of LMWH combined with ASA in the treatment of RSA. METHODS: Randomized controlled trials of LMWH combined with ASA for RSA were searched in the databases of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical Literature Service System from the construction of the database to June 2024. Data were analyzed using Review Manager 5.3 and Stata software. Dichotomous variables were analyzed using relative risk (RR) and 95% confidence interval (CI) as their statistics. The included literature was assessed for bias and risk of bias of eligible studies using Cochrane risk of bias tool. The risk of bias was evaluated based on the evaluation criteria recommended by the Cochrane Guidance Manual for Systematic Evaluation. RESULTS: A total of 32 papers with a total of 3397 patients with RSA were finally included. LMWH combined with ASA treatment significantly improved the live birth rate (RR = 1.31, 95% CI: [1.19, 1.45], P < .00001), the rate of preterm stillbirths (RR = 0.23, 95% CI: [0.13, 0.40], P < .00001), rate of term delivery (RR = 1.55, 95% CI: [1.43, 1.67], P < .00001), rate of miscarriage (RR = 0.42, 95% CI: [0.36, 0.48], P < .00001), incidence of petechiae (RR = 0.44, 95% CI: [0.26, 0.72], P = .001), and incidence of thrombocytopenia (RR = 0.61, 95% CI: [0.39, 0.96], P = .03). In contrast, the incidence of preterm live births (RR = 1.07, 95% CI: [0.90, 1.28], P = .44), adverse reactions (RR = 0.77, 95% CI: [0.59, 1.00], P = .05), gingival bleeding (RR = 1.12, 95% CI: [0.65, 1.93], P = .69), and gastrointestinal reactions (RR = 0.87, 95% CI: [0.64, 1.17], P = .35) were not significant. CONCLUSION: LMWH combined with ASA treatment might improve pregnancy outcomes and reduces the incidence of adverse events in patients with RSA.

Incidence and risk of post-COVID-19 thromboembolic disease and the impact of aspirin prescription; nationwide observational cohort at the US Department of Veteran Affairs.

INTRODUCTION: COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. METHODS: This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. RESULTS: 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). CONCLUSIONS: Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.

Aspirin-clopidogrel combination therapy for ischemic stroke patients: Clinical efficacy and cost-effectiveness analyses in low-resource setting.

Understanding the cost-effectiveness of aspirin-clopidogrel combination therapy is crucial in determining its influence on coagulation parameters, specifically prothrombin time (PT) and activated partial thromboplastin time (APTT). The aim of this study was to assess the cost-effectiveness and clinical impact of using the aspirin-clopidogrel combination compared to aspirin alone in managing ischemic stroke. Employing an observational research design, inpatient ischemic stroke cases receiving the aspirin-clopidogrel combination were compared to those treated with aspirin alone. Focusing on the hospital's perspective on costs, the research specifically analyzed medical expenses without discounting costs or effects. The analysis involved comparing the direct medical costs and coagulation parameters between the two treatment groups. Our data revealed that the aspirin-clopidogrel combination demonstrated superior cost-effectiveness over aspirin alone, indicated by the incremental cost-effectiveness ratio (ICER) values for PT (IDR -246,930/second) and APTT (IDR -119,270/second). This indicated that the combination therapy was associated with lower costs while yielding better clinical parameter values. The ICER analysis placed the aspirin-clopidogrel combination in the southeast quadrant, marking its dominance over aspirin monotherapy by demonstrating higher effectiveness at lower costs. These results suggest that combination therapy might be a favorable alternative for managing ischemic stroke, presenting a viable option for consideration in clinical practice. The findings underscore the potential economic and clinical advantages of employing the aspirin-clopidogrel combination in routine stroke management protocols.

Aspirin for Secondary Prevention of ASCVD is Equally Safe and Effective for Men and Women.

According to this study.

Effects of alteplase and aspirin on functional outcomes in patients with acute ischemic stroke and mild non-disabling neurological deficit.

Investigate the effect of Alteplase and Aspirin on the functional outcomes of patients with acute ischemic stroke with mild non-disabling neurological deficit. In this single-center, randomized controlled study, we selected 60 patients with acute ischemic stroke with mild non-disabling neurological deficit admitted to our hospital from January 2021 to January 2022, and randomly divided them into the study group (n = 30) and the control group (n = 30), the control group was given the Aspirin treatment, the study group was given the Alteplase treatment, and the changes in neurological recovery, daily living ability, exercise ability, balance ability, cognitive function, and short-term prognosis outcomes were observed in these 2 groups. The factors influencing the short-term outcome of Alteplase therapy in patients with acute ischemic stroke were analyzed. The National Institutes of Health Neurological Deficit Score (NIHSS) scores at T1 and T2 of the study group were lower than those in the control group, but the scores of Barthel indicators (BI), Fugl-Meyer Motor Assessment Scale (FMA), Berg Balance Scale (BBS) and Montreal Cognitive Assessment Scale (MoCA) of the study group were higher than those in the control group, and the difference was statistically significant (P < .05). The short-term prognostic outcomes of these 2 groups were not significantly different (P > .05). The effect of the use of Alteplase or Aspirin on short-term functional outcomes in patients with acute ischemic stroke and mild non-disabling neurological deficit is not much different.

Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack.

BACKGROUND AND OBJECTIVES: Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients. METHODS: The INSPIRES trial was a 2*2 factorial placebo-controlled randomized trial conducted in 222 hospitals in China. The 2 treatments did not interact and were evaluated separately. In this study, we performed secondary analyses based on antiplatelet treatment. All patients with mild stroke or TIA of presumed atherosclerotic cause within 72 hours of symptom onset enrolled in the trial were included. Patients were randomly assigned to receive clopidogrel-aspirin on days 1-21 followed by clopidogrel on days 22-90 or aspirin alone for 90 days. The primary efficacy outcome was major ischemic event which included the composite of ischemic stroke and nonhemorrhagic death. The primary safety outcome was moderate-to-severe bleeding. We estimated the risk difference between the 2 treatments for each stratified week. RESULTS: All 6,100 patients in the trial were included (3,050 in each group). The mean age was 65 years, and 3,915 patients (64.2%) were men. Compared with aspirin alone, the reduction of major ischemic events by clopidogrel-aspirin mainly occurred in the first week (absolute risk reduction [ARR] 1.42%, 95% CI 0.53%-2.32%) and remained in the second week (ARR 0.49%, 95% CI 0.09%-0.90%) and the third week (ARR 0.29%, 95% CI -0.05% to 0.62%). Numerical higher risk of moderate-to-severe bleedings in the clopidogrel-aspirin group was observed in the first 3 weeks (absolute risk increase 0.05% [95% CI -0.10% to 0.20%], 0.10% [95% CI -0.09% to 0.29%], and 0.18% [95% CI -0.03% to 0.40%] in the first, second, and third weeks, respectively). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low, but ongoing hemorrhagic risk. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03635749. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, the net benefit of clopidogrel-aspirin initiated within 72 hours of symptom onset was pronounced in the first week and continued to a lesser degree in the following 2 weeks, outweighing the low but ongoing hemorrhagic risk.

Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis Post Hoc Analysis of ATAMIS.

BACKGROUND: We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to investigate whether the priority of clopidogrel plus aspirin to aspirin alone was consistent between patients with and without stroke pathogenesis of large-artery atherosclerosis (LAA). METHODS AND RESULTS: Patients with stroke classification randomized to a clopidogrel-plus-aspirin group and aspirin-alone group in a modified intention-to-treat analysis set of ATAMIS were classified into LAA and non-LAA subtypes. The primary outcome was early neurologic deterioration at 7 days, defined as a >2-point increase in National Institutes of Health Stroke Scale score compared with baseline, and safety outcomes were bleeding events and intracranial hemorrhage. We compared treatment effects in each stroke subtype and investigated the interaction. Among 2910 patients, 225 were assigned into the LAA subtype (119 in the clopidogrel-plus-aspirin group and 106 in the aspirin-alone group) and 2685 into the non-LAA subtype (1380 in the clopidogrel-plus-aspirin group and 1305 in the aspirin-alone group). Median age was 66 years, and 35% were women. A lower proportion of early neurologic deterioration was found to be associated with dual antiplatelet therapy in the LAA subtype (adjusted risk difference, -10.4% [95% CI, -16.2% to -4.7%]; P=0.001) but not in the non-LAA subtype (adjusted risk difference, -1.4% [95% CI, -2.6% to 0.1%]; P=0.06). No significant interaction was found (P=0.11). CONCLUSIONS: Compared with the non-LAA subtype, patients with stroke of the LAA subtype may get more benefit from dual antiplatelet therapy with clopidogrel plus aspirin with respect to early neurologic deterioration at 7 days. REGISTRATION: URL: clinicaltrials.gov; UnIque identifier: NCT02869009.

Clopidogrel Versus Aspirin as Chronic Maintenance Antiplatelet Monotherapy in Patients After Percutaneous Coronary Intervention With Chronic Kidney Disease: A Post Hoc Analysis of the HOST-EXAM Trial.

BACKGROUND: Clopidogrel monotherapy improved clinical outcomes compared with aspirin monotherapy during a chronic maintenance period in patients who underwent coronary stenting in the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it is uncertain whether the beneficial effect of clopidogrel over aspirin is different according to the renal function. METHODS AND RESULTS: We conducted a post hoc analysis of the HOST-EXAM trial. Chronic kidney disease (CKD) was defined as baseline estimated glomerular filtration rate <60 mL/min per 1.73 m2. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type ≥3, during the 2-year follow up. Among the 5438 patients enrolled in the HOST-EXAM trial, 4844 patients (mean age, 63.3±10.6 years; 74.9% men) with a baseline creatinine value were analyzed in this study. A total of 508 (10.5%) patients had CKD, who were at higher risk of the primary end point compared with those without CKD (hazard ratio [HR], 2.01 [95% CI, 1.51-2.67]). Clopidogrel monotherapy was associated with a lower rate of the primary end point in both patients with CKD (HR, 0.74 [95% CI, 0.44-1.25]) and patients without CKD (HR, 0.71 [95% CI, 0.56-0.91]). No significant interaction was observed between the treatment effect and CKD status (P for interaction=0.889). CONCLUSIONS: During the chronic maintenance period after coronary stenting, the risk of thrombotic and bleeding events was significantly higher in patients with CKD compared with those without CKD. There was no statistical difference in the treatment effect of clopidogrel monotherapy in those with versus without CKD.

Clopidogrel and Aspirin Initiated Between 24 to 72 Hours for Mild Ischemic Stroke: A Subgroup Analysis of the INSPIRES Randomized Clinical Trial.

Importance: Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window. Objective: To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). Patients were followed up for 90 days. Interventions: All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. Main Outcomes and Measures: The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Results: This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%) among those randomized from more than 24 hours to 48 hours, and in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (P = .38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (P = .92 for interaction). Conclusions and Relevance: In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.

Antithrombotic Therapy in Patients Undergoing Peripheral Artery Interventions.

Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.

Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

The role of aspirin in the prevention of pancreatic cancer: A nested case-control study in the UK Biobank.

BACKGROUND: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) usage has been associated with pancreatic ductal adenocarcinoma (PDAC) prevention, though epidemiological data have not reliably demonstrated this. The aim of this study is to identify if aspirin and other NSAIDs are effective in the primary prevention of PDAC in a large UK prospective cohort. METHODS: A nested case-control study was conducted using the UK Biobank cohort. Incident PDAC cases (n = 1129 of whom 239 (21.2 %) were using aspirin) were age and sex-matched with cancer-free controls (n = 8822 of whom 1752 (19.9 %) were using aspirin). Conditional logistic regression models were used to generate odds ratios (ORs) and 95 % confidence intervals (CI) for risk of PDAC with and without regular use of aspirin, non-aspirin NSAIDs and all NSAIDs respectively. Exploratory analyses were carried out assessing interactions with diabetes mellitus (DM) as a condition with increased pancreatic cancer risk. RESULTS: Regular aspirin use at initial recruitment was independently associated with a decreased risk of PDAC (OR [95 % CI] = 0.80 [0.68-0.95] P = 0.01). Regular non-aspirin NSAID use was not associated with a risk reduction of PDAC (OR [95 % CI] = 1.01 [0.84-1.23] P = 0.88). Exploratory analyses showed that in those with DM; regular aspirin use reduced risk of PDAC (OR [95 % CI] = 0.60 [0.42-0.85] P = 0.004) compared to non-use. DISCUSSION: Regular aspirin use is associated with a reduction in risk of PDAC. The reduced risk is more apparent in participants with DM.

Antithrombotic prophylaxis following total knee arthroplasty: a level I Bayesian network meta-analysis.

INTRODUCTION: Venous thromboembolism (VTE) is a major concern following total knee arthroplasty (TKA). The optimal pharmacological prophylaxis remains, however, controversial. The present investigation compared several non-vitamin K antagonist oral anticoagulants commonly employed as VTE prophylaxis following TKA. A Bayesian network meta-analysis was conducted to compare apixaban, aspirin, dabigatran, edoxaban, enoxaparin, fondaparinux, and rivaroxaban. The outcomes of interest were to compare the rate of deep venous thrombosis (DVT), pulmonary embolism (PE), and major and minor haemorrhages. METHODS: This study was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. In March 2024, PubMed, Web of Science, and Google Scholar were accessed with no time constraints. All randomised controlled trials (RCTs) comparing two or more drugs for the prevention of VTE following TKA were considered for inclusion. RESULTS: Data from 29,678 patients were collected. Of them, 67% (19,884 of 29,678 patients) were women. The mean age of the patients was 66.8 ± 2.8 years, and the mean BMI was 29.2 ± 1.5 kg/m2. There was comparability in age, sex, and BMI at baseline. Apixaban 5 mg, dabigatran 220 mg, and rivaroxaban 10 mg were the most effective in reducing the rate of DVT. Apixaban 5 mg, enoxaparin 60 mg, and rivaroxaban 40 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, rivaroxaban 10 mg, and apixaban 10 mg were associated with the lowest rate of major haemorrhages. Apixaban 5 mg and 20 mg, and dabigatran 220 mg were associated with the lowest rate of minor haemorrhages. CONCLUSION: Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following TKA. LEVEL OF EVIDENCE: Level I, network meta-analysis of RCTs.

Vitamin-K antagonist versus dual antiplatelet therapy in management of isolated and non-obstructive atherosclerotic coronary artery ectasia.

BACKGROUND: Treatment of isolated and non-obstructive atherosclerotic coronary artery ectasia (CAE) is still controversial. AIM: To assess the efficacy and safety of vitamin-K antagonist (VKA) versus dual antiplatelet (DAPT) therapy in management of patients with isolated and non-obstructive atherosclerotic CAE. METHODS: We prospectively enrolled 79 patients diagnosed on elective coronary angiography to have either isolated CAE or non-obstructive atherosclerotic CAE. Patients were assigned in 1:1 pattern to receive either VKA (warfarin) or DAPT (aspirin plus clopidogrel). Patients were followed-up for nine-months. The primary endpoint was the cumulative events rate including acute coronary event, target vessel intervention, or cardiac death. Analysis of cumulative events at different time intervals, its individual components, and bleeding were considered secondary endpoints. RESULTS: Cumulative events rate was 33%, with mortality rate of 2.5%. Both treatment groups showed comparable cumulative events during the nine-months follow-up duration. Nevertheless, Kaplan-Meier analysis beyond the first 3-months of follow-up showed significantly higher event-free survival among the VKA-group. Recurrent events (≥2) were significantly higher among the DAPT-group. Both groups showed no major bleeding events. Multivariable cox-regression analysis showed that presence of significant coronary tortuosity, use of DAPT in reference to VKA, and lower percent time in therapeutic range (%TTR) among those receiving VKA were significant independent predictors of clinical adverse events beyond the first 3-months of follow-up. CONCLUSION: Cumulative adverse events were comparable among both treatment groups for isolated non-obstructive CAE. However, adverse events were significantly more frequent in the DAPT-group beyond the first three months.

Isolated ipsilateral ptosis associated with ventral midbrain infarction: a case report and literature review.

Documented cases of ipsilateral ptosis caused by midbrain infarction remain rare. Herein, we present a patient with isolated ipsilateral ptosis that was initially considered to be a consequence of myasthenia gravis but was subsequently attributed to ventral midbrain infarction. We also discuss the possible underlying mechanisms; ipsilateral ptosis in our patient was attributed to selective damage of the levator palpebral muscle branch of the oculomotor nerve. The patient was started on aspirin (200 mg once daily) and atorvastatin (40 mg once daily). Improvement in ptosis occurred from day 5 of admission, and the patient was subsequently discharged. Ptosis disappeared 1 month after onset. This report describes an extremely rare case of ventral midbrain infarction presenting with isolated ipsilateral ptosis. Careful examination, including magnetic resonance imaging, is essential in such patients, especially in those with multiple cerebrovascular risk factors.

Aspirin use in patients with elevated lipoprotein(a): Impact on cardiovascular events and bleeding.

The role of aspirin in cardiovascular primary prevention remains controversial. There are physiological reasons to explore its potential benefits in patients with high levels of lipoprotein(a) [Lp(a)], mainly due to its antifibrinolytic properties and interactions with platelets. The primary objective of this systematic review was to evaluate the cardiovascular benefits and bleeding risks associated with aspirin use in patients who have elevated Lp(a) levels but no history of cardiovascular disease. This systematic review was conducted following PRISMA guidelines. We performed a literature search to identify studies assessing the cardiovascular benefits and bleeding risks of aspirin use in patients with elevated Lp(a) levels (or a related genetic variant) who have no history of cardiovascular disease. Five studies (49,871 individuals) were considered for this systematic review. Three studies assessed the impact of aspirin use in relation to genetic variants associated with elevated Lp(a) levels (SNP rs379822), while the remaining two studies directly measured plasma levels of Lp(a). The endpoints evaluated varied among the studies. Overall, the findings consistently show that carriers of the apolipoprotein(a) variant or patients with Lp(a) levels > 50 mg/dL experience a reduction in cardiovascular risk with aspirin use. No significant bleeding issues were observed, although such events were reported in only two studies. This systematic review suggests that aspirin use in patients with elevated Lp(a) levels and no prior cardiovascular history may reduce cardiovascular risk. The available data on bleeding risk is insufficient.