Low-dose Aspirin Research Articles

Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices: The DOAC LVAD Study

BackgroundPatients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described. ObjectivesThis study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non–central nervous system thromboembolism) as compared with treatment with warfarin. MethodsThe DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome. ResultsA total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources. ConclusionsAnticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978)

Barriers and facilitators of adherence to low-dose aspirin during pregnancy: A co-produced systematic review and COM-B framework synthesis of qualitative evidence.

Women at increased risk of developing pre-eclampsia are advised to take a daily low-dose of aspirin from 12 weeks of pregnancy to reduce their risks. Despite the well-established prophylactic effect of aspirin, adherence to this therapy is low. This systematic review aimed to summarise evidence on the barriers and facilitators of adherence to low-dose aspirin to inform intervention development to support decision making and persistence with aspirin use for pre-eclampsia prevention. A systematic review and meta-synthesis of qualitative research was co-produced by representatives from charities, and public, clinical and academic members. Eight electronic databases (MEDLINE, PsycINFO, CINAHL, Web of Science, Scopus, EMBASE, Prospero, OpenGrey), archives of charities and professional organisations were searched (between October and November 2023 and re-run in August 2023) using predefined search terms. Studies containing qualitative components related to barriers and facilitators of adherence to low-dose aspirin during pregnancy were included. Quality assessment was performed using the Critical Appraisal Skills Programme checklist for qualitative research. A combination of the COM-B framework with phases of adherence process as defined by international taxonomy was used as the coding framework. Co-production activities were facilitated by use of 'Zoom' and 'Linoit'. From a total of 3377 papers identified through our searches, five published studies and one dissertation met our inclusion criteria. Studies were published from 2019 to 2022 covering research conducted in the USA, Canada, UK, Netherlands and Australia. Barriers and facilitators to adherence were mapped to six categories of the COM-B for three phases of adherence: initiation, implementation, and discontinuation. The discontinuation phase of adherence was only mentioned by one author. Four key themes were identified relating to pregnancy: 'Insufficient knowledge', 'Necessity concerns balance', 'Access to medicine', 'Social influences', and 'Lack of Habit'. The COM-B framework allowed for detailed mapping of key factors shaping different phases of adherence in behavioural change terms and now provides a solid foundation for the development of a behavioural intervention. Although potential intervention elements could be suggested based on the results of this synthesis, additional co-production work is needed to define elements and plan for the delivery of the future intervention. PROSPERO CRD42022359718. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359718.

Abstract 3097: Platelet COX-1 Dependent And Independent Heterogeneity In Response To Low-Dose Aspirin

Background: Platelets are key mediators of thrombosis and hemostasis. While aspirin decreases cardiovascular events in high-risk populations, its pharmacological and therapeutic effect is limited by heterogeneity in response and its effect on COX-1 dependent and independent pathways. We sought to investigate the heterogeneity of response of low-dose (81mg/day) aspirin. Methods: Following an overnight fast, 39 healthy controls had 4 weekly phlebotomies and received 81 mg aspirin daily between weeks 3 and 4. At each collection, platelet activity was measured using light transmission aggregation (LTA) in response to arachidonic acid (AA [1.5 mM]; COX-1 dependent ) and epinephrine (2.0 μM), ADP (2.0 μM), and collagen (1.0 μM; COX-1 independent pathways). Results: Median age was 27 (21, 59) years, 48.7% were female, 53.9% were white, and 7.7% were Hispanic. Median platelet aggregation in response to AA (1.5 mM) was 90.9%, 91.6%, and 91.4% in weeks 1, 2, and 3, demonstrating a robust reproducible response. Baseline AA-induced platelet aggregation was modestly correlated with ADP- (r=0.28, p=0.054), collagen- (r=0.42, p=0.0036), and epinephrine-induced (r=0.32, p=0.029) platelet aggregation. Following 1 week of aspirin, AA-induced platelet aggregation decreased to 11.8% (p<0.0001). The median (interquartile range) platelet inhibition in response to AA was 87.3% (78.5%, 92.5%) demonstrating a robust COX-1 dependent response. Platelet inhibition in response to epinephrine (52.1% [46.4, 62.6]), collagen (79.5% [70.3, 87.4]), and ADP (29.8% [22.0, 36.0]), albeit statistically significant, was less robust. While platelet inhibition in response to AA was correlated to platelet inhibition in response to collagen (r=0.64 p=1.12E-5) and epinephrine (r=0.44, p=0.0052), there was no correlation in response to ADP (r=-0.04, p=0.81) induced platelet inhibition. Conclusions: Our findings demonstrate a robust COX-1 dependent aggregation response and a more heterogeneous COX-1 independent aggregation response to low-dose aspirin. The mechanism and clinical significance of these findings require further study.

EFFICACY OF ACETYLSALICYLIC ACID COMBINED WITH GLUCOCORTICOID IN THE TREATMENT OF TAKAYASU ARTERITIS: CASE REPORT

Objective: Takayasu arteritis (TA) is an idiopathic large-vessel vasculitis, predominantly impacting the aorta and its major branches. The management of TA includes pharmacotherapy or surgical intervention in the presence of complications. Design and method: A 14-year-old girl was admitted to our clinic for a thoracic aortic aneurysm. Initial symptoms include fever, loss of appetite, weight loss, muscle pain, followed by palpitations and abdominal pain, and loose stools. The test showed an increased hs-CRP level: 28.7 mg/L. Computed tomography angiography (CTA) chest with contrast showed two segments of thoracic aneurysms involving descending aorta, the aortic diameter of the superior and inferior segment aneurysms is #1.6-1.8 cm, #2x 2.1 cm, respectively, and the length is #2.5 cm, # 3.2 cm, respectively. According to JSC 2017, This patient was diagnosed with descending aorta aneurysms in Takayasu arteritis- type III (ACR 1994) The patient underwent corticosteroid therapy, starting with prednisolone at an initial dose of 20 mg/day. The dosage was reduced to 10 mg/day at month 3 and maintained at 5 mg/day from month 6 until the completion of the 18-month therapy. Additionally, low-dose aspirin (81 mg/day), ACE inhibitors, and beta-blockers were incorporated to enhance treatment efficacy. Results: After 3 months, hs-CRP levels returned to normal. After 12 months of combined treatment with corticosteroids and aspirin as described above, the patient's aortic diameter had returned to almost normal on CTA. The patient's symptoms improved after finishing treatment. Conclusions: Successful treatment of Takayasu arteritis in our case, highlights the significant role of pharmacotherapy. This cost-effective approach minimizes side effects, offering promising treatment options for Takayasu arteritis patients, especially in low-income countries like Vietnam

A Quality Improvement Project in Family Medicine Residency Training: Improving Preeclampsia Prevention Through Risk Factor Screening and Low-Dose Aspirin.

Providing aspirin during pregnancy is a critical intervention proven to reduce the rates of preeclampsia in patients at risk. This quality improvement project prepared family medicine residents to use public health strategies to improve screening of pregnant patients at risk for preeclampsia in an underserved population. A preeclampsia awareness campaign was launched utilizing a publicly available toolkit, while a multidisciplinary team implemented systemic clinical changes to increase the rates of preeclampsia risk factor screening and aspirin prescription to prevent preeclampsia. (Am J Public Health. 2024;114(S4):S318-S321. https://doi.org/10.2105/AJPH.2024.307667).

Abstract 2097: Jak2 V617f Clonal Hematopoiesis Promotes Arterial Thrombosis Via Platelet Activation And Cross-talk

JAK2 V617F ( JAK2 VF ) clonal hematopoiesis (CH) is associated with a marked increase in atherothrombotic cardiovascular disease (CVD). The role of JAK2 VF CH in arterial thrombosis has not been assessed. Using mice simulating JAK2 VF CH, we showed accelerated carotid artery thrombosis, with increased platelet counts and activation and increased leukocytes and red blood cells. There was increased platelet activation in both Jak2 VF and wild type (WT) platelets in Jak2 VF CH suggesting cross-talk between mutant and WT platelets. To assess platelet-specific effects, we used Gp1ba-Cre (VFGp1ba) to selectively express Jak2 VF in platelets. VFGp1ba increased platelet counts to a similar level as in 20% Jak2 VF CH mice but had no effect on leukocyte counts. Like Jak2 VF CH, VFGp1ba increased platelet activation and accelerated arterial thrombosis. Mechanistically, Jak2 VF platelets showed 2.8-fold up-regulation of COX-1, increased activation of cytosolic phospholipase A2, an enzyme important for arachidonic acid generation, and increased thromboxane A2 production. Conditioned media from activated Jak2 VF platelets induced WT platelet activation that was reversed by a thromboxane receptor antagonist. Low dose aspirin ameliorated carotid thrombosis in VFGp1ba and Jak2 VF CH but not in WT control mice. This study shows increased arterial thrombosis in Jak2 VF CH related to Jak2 VF platelet activation and cross-talk with WT platelets via thromboxane, suggesting a potential beneficial role of aspirin treatment in JAK2 VF CH.

Adjunctive Cilostazol in Patients With High Residual Platelet Reactivity After Drug-Eluting Stent Implantation: A Randomized, Open-Label, Single-Center, Prospective Study (ADJUST-HPR).

Cilostazol as an adjunct to dual antiplatelet therapy (DAPT) postcoronary stenting may further reduce vascular occlusion risks. The aim of this study was to assess the impact of cilostazol on high residual platelet reactivity (HRPR) in patients undergoing drug-eluting coronary stent implantation. In a randomized, open-label, single-center, prospective study, the degree of platelet inhibition by cilostazol 100 mg twice daily was assessed on top of conventional DAPT compared with standard clopidogrel and low-dose aspirin combination in poststent patients with HRPR. HRPR was defined as P2Y12 units (PRU) > 240 as measured by the VerifyNow P2Y12 assay. In addition, the platelet activity was assessed by light transmittance aggregometry (LTA) and Multiplate electrode analyzer (MEA). The total of 148 patients were screened, and HRPR was observed in 64 (43.2%). Those were randomized for DAPT versus triple therapy (TAPT). After 30 days, TAPT group exhibited significantly lower rate of HRPR when assessed by all 3 devices (VerifyNow: 40.0 vs. 66.7% P = 0.04, LTA: 6.7 vs. 30.0% P = 0.02, MEA: 10.0 vs. 30.0% P = 0.05 L all vs. DAPT). Also, higher absolute mean difference in TAPT versus DAPT group after 30 days (VerifyNow: 71.3 ± 38.2 vs. 24.6 ± 40.2 P < 0.001, LTA: 23.9 ± 15.1 vs. 9.4 ± 11.8 P < 0.001, MEA: 9.3 ± 12.9 vs. 2.4 ± 17.3 P = 0.08) was observed. Cilostazol in addition to standard DAPT reduces the incidence of HRPR and diminishes further platelet activity in poststent patients. Whether this favorable laboratory finding will affect clinical outcomes requires an adequately powered randomized trial.

Low-Dose Aspirin for Optimization of Postpartum Vascular Recovery Following Severe Preeclampsia: A Pilot Study

Low-Dose Aspirin for Optimization of Postpartum Vascular Recovery Following Severe Preeclampsia: A Pilot Study

Saudi National Clinical Practice Guidelines for Management of Adult Systemic Lupus Erythematosus.

To provide evidence-based clinical practice recommendations for managing Systemic Lupus Erythematosus (SLE) in Saudi Arabia. This EULAR-adapted national guideline in which a multidisciplinary task force utilized the modified Delphi method to develop 31 clinical key questions. A systematic literature review was conducted to update the evidence since the EULAR publication. After reaching a consensus agreement, two rounds of voting and group discussion were conducted to generate consolidated recommendations/statements. A significant number of patients in Saudi Arabia experience delays in accessing rheumatologists, highlighting the significance of timely referral to SLE specialists or rheumatologists to ensure accurate diagnosis and prompt treatment. The primary goal of Glucocorticoid (GC) therapy in SLE patients is to establish disease control with a minimum dose and duration. Steroid-sparing agent utilization facilitates steroid-sparing goals. Hydroxychloroquine is recommended for all SLE patients, though physicians must carefully monitor toxicity and prioritize regular medication adherence assessment. SLE management during pregnancy starts from preconception time by assessing disease activity, major organ involvement, hypercoagulability status, and concomitant diseases that may negatively impact maternal and fetal outcomes. Multidisciplinary care with close monitoring may optimize both maternal and fetal outcomes. For patients with antiphospholipid antibodies, low-dose aspirin prophylaxis is recommended. Also, Long-term anticoagulant medications are fundamental to prevent secondary antiphospholipid syndrome due to high thrombosis recurrence. This Saudi National Clinical Practice guidelines for SLE management provide evidence-based recommendations and guidance for healthcare providers in Saudi Arabia who are managing patients with SLE. These guidelines will help to standardize healthcare service, improve provider education, and perhaps lead to better treatment outcomes for SLE patients.

Low-dose aspirin increases olfactory sensitivity in association with enhanced neurogenesis and reduced activity of AChE in the experimental aging mice

This study examined the effect of aspirin on olfactory discrimination and neurogenesis in experimental aging mice. The results from the buried food test (BFT) and odour preference test (OPT) indicated that aspirin treatment enhanced the olfactory functions in the experimental animals. The immunohistochemical assessment revealed increased amounts of doublecortin (DCX)-positive immature neurons and bromodeoxyuridine (BrdU)/neuronal nuclei (NeuN) double-positive new neurons in the olfactory bulb (OB) of aspirin-treated animals compared to the control group. Besides, aspirin treatment resulted in a decreased number of ionized calcium-binding adaptor molecule (Iba)-1 positive microglia, a main cellular element of neuroinflammation in the brain compared to the control group. In addition, the increased activities of key antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in OB of the aspirin-treated mice were evident. Acetylcholinesterase (AChE) is a key enzyme that hydrolyses acetylcholine (ACh), an important neurotransmitter, involved in cognition, and olfaction. While the enhanced activity of AChE has been linked to the severity of dementia and OB defects, the biochemical assessments indicated reduced activity of AChE in OB-derived homogenates of the aspirin-treated experimental animals than that of the control group. Taken together, this study validates the proneurogenic, cholinergic, and anti-neuroinflammatory properties of aspirin in the OB which can be considered in boosting neural regeneration and management of olfactory deficits in aging and various disorders.

Comparison of Pre-eclampsia Screening Algorithms in the First Trimester of Pregnancy Being Used in Thai Nguyen Province.

Objective To compare the rates of pregnancies in high-risk groups for preeclampsia recommended for aspirin prophylactic when screened using various common algorithms. Methods This cross-sectional study was conducted on 1726 pregnant women from 11 to 13 weeks six days of gestation receiving antenatal care at two hospitals: Thai Nguyen National Hospital and a hospital in Thai Nguyen Province from October 2022 to October 2023. All participants provided consent for the study. We collected maternal characteristics, obstetric history,mean arterial pressure (MAP), mean uterine artery-PI (UtA-PI), and placental growth factor serum (PLGF). Screening performance estimates were calculated using the Fetal Medicine Foundation (FMF) and National Institute for Health and Care Excellence (NICE) guidelines. All pregnant women in the study had their preeclampsia risk assessed using all three algorithms with two cut-off points.Our data was collected, entered and analyzed using SPSS software 20.0 (IBM Corp., Armonk, NY). Categorical data was reported as frequency and percentage. McNemar's test was used for analyzing differences in the sizes of individual groups. Results In our study, the most common high-risk factor identified was the history of preeclampsia, 132 cases (7.6%). According to the NICE guideline, BMI ≥ 35 (kg/m²) is considered a moderate risk factor for preeclampsia. Several risk factors, such as BMI ≥ 35 kg/m² and history of diabetes mellitus type 1, were not present in any participants. Only one pregnant woman had chronic kidney disease (0.06%). Out of the 1726 pregnant women surveyed, the rates of high-risk preeclampsia were as follows: 9.9% (171 cases) based on algorithm 1; 10.8% (187 cases) based on algorithm 2 with a cut-off point > 1/100, 11.8% (203 cases) with a cut-off point > 1/150; 10.3 % (178 cases) based on algorithm 3 with a cut-off point > 1/100, and 11.6% (201 cases) with a cut-off point > 1/150. Among these algorithms, pregnant women in the high-risk preeclampsia group were advised to consider taking low-dose aspirin. Conclusion Screening for pre-eclampsia based on NICE recommendations resulted in a lower number of high-risk pregnant women requiring prophylactic aspirin use compared to other algorithms. This means that some pregnant women at risk of developing preeclampsia are not recommended to use aspirin as a preventive measure. Adding PLGF to the screening strategy will help us get closer to pregnant women who are truly at risk of progressing to preterm preeclampsia.

Differential Impact In Vivo of Pf4-ΔCre-Mediated and Gp1ba-ΔCre-Mediated Depletion of Cyclooxygenase-1 in Platelets in Mice.

Low-dose aspirin is widely used for the secondary prevention of cardiovascular disease. The beneficial effects of low-dose aspirin are attributable to its inhibition of platelet Cox (cyclooxygenase)-1-derived thromboxane A2. Until recently, the use of the Pf4 (platelet factor 4) Cre has been the only genetic approach to generating megakaryocyte/platelet ablation of Cox-1 in mice. However, Pf4-ΔCre displays ectopic expression outside the megakaryocyte/platelet lineage, especially during inflammation. The use of the Gp1ba (glycoprotein 1bα) Cre promises a more specific, targeted approach. To evaluate the role of Cox-1 in platelets, we crossed Pf4-ΔCre or Gp1ba-ΔCre mice with Cox-1flox/flox mice to generate platelet Cox-1-/- mice on normolipidemic and hyperlipidemic (Ldlr-/-; low-density lipoprotein receptor) backgrounds. Ex vivo platelet aggregation induced by arachidonic acid or adenosine diphosphate in platelet-rich plasma was inhibited to a similar extent in Pf4-ΔCre Cox-1-/-/Ldlr-/- and Gp1ba-ΔCre Cox-1-/-/Ldlr-/- mice. In a mouse model of tail injury, Pf4-ΔCre-mediated and Gp1ba-ΔCre-mediated deletions of Cox-1 were similarly efficient in suppressing platelet prostanoid biosynthesis. Experimental thrombogenesis and attendant blood loss were similar in both models. However, the impact on atherogenesis was divergent, being accelerated in the Pf4-ΔCre mice while restrained in the Gp1ba-ΔCres. In the former, accelerated atherogenesis was associated with greater suppression of PGI2 biosynthesis, a reduction in the lipopolysaccharide-evoked capacity to produce PGE2 (prostaglandin E) and PGD2 (prostanglandin D), activation of the inflammasome, elevated plasma levels of IL-1β (interleukin), reduced plasma levels of HDL-C (high-density lipoprotein receptor-cholesterol), and a reduction in the capacity for reverse cholesterol transport. By contrast, in the latter, plasma HDL-C and α-tocopherol were elevated, and MIP-1α (macrophage inflammatory protein-1α) and MCP-1 (monocyte chemoattractant protein 1) were reduced. Both approaches to Cox-1 deletion similarly restrain thrombogenesis, but a differential impact on Cox-1-dependent prostanoid formation by the vasculature may contribute to an inflammatory phenotype and accelerated atherogenesis in Pf4-ΔCre mice.

P031 An case of cryofibrinogen associated necrotising cutaneous vasculitis on background of aortitis

Abstract Background/Aims Cryofibrinogen is an abnormal protein that forms precipitate in plasma but not in serum. Cryofibrinogenaemia can be detected in healthy individuals and patients with autoimmune diseases, cancer, and infections. Current data suggest that isolated cryofibrinogenaemia can be detected in up to 3% of healthy individuals and it is usually asymptomatic. However, cryofibrinogenaemia can be associated with systemic inflammatory manifestations, of which cutaneous involvement is the most prominent. Methods A 76-year-old male patient presented with acute and progressive necrotising ulcers in the lower limbs along with high inflammatory markers and general decline. He had a background of large vessel vasculitis (aortitis), which was diagnosed with a PET-CT scan three years prior to the current presentation. He was previously treated with oral steroids and eight cycles of cyclophosphamide demonstrating an excellent response with complete resolution of the aortitis on the follow-up PET-CT scan. The patient had remained on maintenance treatment with azathioprine (3mg/kg) as well as therapeutic anticoagulation for atrial fibirillation. Results After thorough investigations for an infective cause and poor response to broad spectrum antibiotics, he was reviewed further for recurrence of large vessel vasculitis. A CT angiogram showed concentric symmetrical soft tissue thickening surrounding the thighs and lower limb arteries without luminal stenosis, suggestive of periarterial inflammation. A further MR angiogram of the aorta did not confirm any evidence of aortic, iliac or visceral artery stenosis. A CT chest/abdomen/pelvis excluded any other pathology or malignancy. Additional investigations showed negative ANA and ENA screen, rheumatoid factor, antiphospholipid antibodies, cryoglobulins, hepatitis virus screen, whilst complement and immunoglobulin levels were normal. However, cryofibrinogen was reported positive and a diagnosis of cryofibrinogen-associated necrotising cutaneous vasculitis was concluded. The patent was started on IV cyclophosphamide (15mg/kg) along with IV methylprednisolone (250mg for the first 3 doses) along with each pulse therapy. After the first two pulses, the patient had a favourable clinical and serological response to the immunosuppressive treatment with improvement in cutaneous lesions and significant reduction in the inflammatory markers. He subsequently underwent an angioplasty for tightly stenotic/occluded tibioperoneal trunk with good recanalisation. Conclusion This is a rare overlap syndrome of new-onset small vessel necrotising cutaneous vasculitis on previous background of large vessel disease (aortitis). In most severe cases with essential cryofibrinogenaemia, the mainstay treatment is with corticosteroids and other immunosuppressive agents in combination with oral anticoagulants and/or low-dose aspirin. Post treatment, the risk of relapse remains high and immunosuppressive therapy may only have a limited impact on the course of thrombotic vasculopathy in the absence of inflammation. More research and longitudinal data are required to optimise treatment protocols and outcomes in patients with cryofibrinogen-associated systemic vasculitis. Disclosure A. Psarras: None. J. David: None. R. Luqmani: None. S. Dubey: Consultancies; Boehringer Ingelheim. Member of speakers’ bureau; Janssen.

Restore Veto Property in Low Dose Aspirin/ASA Treated Preeclampsia Placenta Mesenchymal Stem Cells: Insights Into ASA-mediated Clinical Response*

Preeclampsia (PE) is a pregnancy complication characterized by elevated blood pressure, proteinuria, and other laboratory abnormalities. PE affects 2–8% of pregnancies globally and can lead to preterm birth and other complications for the mother and fetus. Successful pregnancy depends on the ability of the mother’s immune system to tolerate the allogeneic fetus. However, in PE, this immune tolerance is exacerbated by inflammation. Transforming growth factor β (TGF-β) is important to retain an immune balance in healthy pregnancy. In PE, TGF-β level is reduced, with an imbalance of the T-cell subset pool to favor inflammation. Omics studies by our group reported an increase in TGF-β signaling when PE-derived placenta mesenchymal stem cells (P-MSCs) were treated with low dose aspirin (ASA). This correlated with increased cycling quiescence and epigenetic changes, resembling healthy P-MSCs. This study tested the hypothesis that ASA could restore the veto property of P-MSCs to mitigate inflammation. ASA (10 mM) treated P-MSCs from PE and healthy placentas increased TGFβ1 and its receptor. The ASA treated MSCs, when added as third-party cells to a one-way mixed lymphocyte reaction, suppressed T-cell proliferation. Prediction studies with omics data indicated that ASA-mediated TGFβ signaling could explain ASA-induced blunting of cell apoptosis. Together, the findings support ASA-mediated expression of TGFβ1 and its receptor on P-MSCs from PE to restore the ability to be licensed as immune suppressor to mitigate PE inflammation. The findings provide new insight into the benefit of ASA treatment for PE.

On-X aortic valve replacement patients treated with low-dose warfarin and low-dose aspirin.

To assess if warfarin targeted to international normalized ratio (INR) 1.8 (range 1.5-2.0) is safe for all patients with an On-X aortic mechanical valve. This prospective, observational registry follows patients receiving warfarin targeted at an INR of 1.8 (range 1.5-2.0) plus daily aspirin (75-100 mg) after On-X aortic valve replacement. The primary end point is a composite of thromboembolism, valve thrombosis and major bleeding. Secondary end points include the individual rates of thromboembolism, valve thrombosis and major bleeding, as well as the composite in subgroups of home or clinic-monitored INR and risk categorization for thromboembolism. The control was the patient group randomized to standard-dose warfarin (INR 2.0-3.0) plus daily aspirin 81 mg from the PROACT trial. A total of 510 patients were enroled at 23 centres in the UK, USA and Canada. Currently, the median follow-up duration is 3.4 years, and median achieved INR is 1.9. The primary composite end point rate in the low INR patients is 2.31% vs 5.39% (95% confidence interval 4.12-6.93%) per patient-year in the PROACT control group, constituting a 57% reduction. Results are consistent in subgroups of home or clinic-monitored, and high-risk patients, with reductions of 56%, 57% and 57%, respectively. Major and total bleeding are decreased by 85% and 73%, respectively, with similar rates of thromboembolic events. No valve thrombosis occurred. Interim results suggest that warfarin targeted at an INR of 1.8 (range 1.5-2.0) plus aspirin is safe and effective in patients with an On-X aortic mechanical valve with or without home INR monitoring.

Needs-based considerations for the role of low-dose aspirin along the CV risk continuum

Cardiovascular disease (CVD) remains the leading cause of death worldwide. The risk of a cardiovascular (CV) event is not static and increases along a continuum, making identification and management complex.Aspirin has been the cornerstone of antiplatelet therapy in CV risk reduction and remains the only antiplatelet agent with current guideline recommendations throughout the CV risk continuum. In light of recent trials, the role of aspirin in CVD prevention in asymptomatic patients has been downgraded in clinical guidelines. However, a substantial proportion of asymptomatic patients have underlying conditions, such as advanced subclinical atherosclerosis that are associated with high CV risk. Advanced subclinical atherosclerosis has not been extensively investigated in patients in clinical trials but in the absence of significant bleeding risks, patients with subclinical atherosclerosis may particularly benefit from preventive aspirin therapy.Recent studies and clinical guidelines support the need for a personalized treatment approach for these patients, balancing their risk of future CV events against their relative bleeding risk. In this commentary, we first discussed various tools and strategies currently available for assessing CV and bleeding risks; we then provided two hypothetical cases to outline how these tools can be implemented for optimal management of patients with no prior CV events who, nonetheless, are susceptible to CVD.The first case details a young and apparently healthy patient with underlying advanced subclinical atherosclerosis; whereas the second case describes a patient with recently diagnosed type 2 diabetes mellitus who is at higher risk of CVD than their non-diabetic counterparts. For both cases, we considered patient clinical characteristics, CV and bleeding risks, as well as other risk factors to evaluate the appropriate treatment strategy and determine whether patients would obtain a net clinical benefit from low-dose aspirin therapy. These cases can serve as examples to guide clinical decision-making on the use of low-dose aspirin for primary CVD prevention and improve CVD management via a personalized approach.

Low-dose aspirin for the prevention of preterm birth in nulliparous women: systematic review and meta-analysis

ObjectiveThe objective was to assess the efficacy and safety of low-dose aspirin for the prevention of preterm birth in nulliparous women.Data sourcesWe searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to June 2022.Study eligibility criteriaRandomized controlled trials that compared aspirin to placebo in nulliparous women were eligible.MethodsThis study was reported in accordance with the PRISMA 2020 checklist. The primary outcomes of this study were the rates of preterm birth at less than 37 weeks and less than 34 weeks of gestation. The secondary outcomes included postpartum hemorrhage, placental abruption, cesarean section, any hypertensive disorder of pregnancy and small for gestational age. Relative risks with their 95% confidence intervals were calculated for analysis. Heterogeneity was assessed by Cochran’s Q test and Higgins’s I2. A random-effects model was used when I2 was > 50% to generate the RR and 95% CI; otherwise, a fixed-effects model was used. The risk of publication bias was assessed by funnel plots. We performed sensitivity analysis by sequentially omitting each included study to confirm the robustness of the analysis.ResultsSeven studies with a total of 29,029 participants were included in this review. Six studies were assessed as having a low risk of bias or an unclear risk of bias, and one study was judged as having a high risk of bias. In nulliparous women, low-dose aspirin was associated with a significant reduction in the rate of preterm birth at less than 34 weeks of gestational age (RR 0.84,95% CI: 0.71–0.99; I2 = 0%; P = 0.04), but we did not observe a significant difference in the rate of preterm birth at less than 37 weeks of gestation (RR 0.96,95% CI: 0.90–1.02; I2 = 31%; P = 0.18). Low-dose aspirin was associated with a significant increase in the rates of postpartum hemorrhage (RR 1.32,95% CI: 1.14–1.54; I2 = 0%; P = 0.0003), placental abruption (RR 2.18,95% CI: 1.10–4.32; I2 = 16%; P = 0.02) and cesarean section (RR 1.053, 95% CI: 1.001–1.108; I2 = 0%; P = 0.05) in nulliparous women. We also did not observe a significant effect of low-dose aspirin on the rates of any hypertensive disorder of pregnancy (RR 1.05, 95% CI: 0.96–1.14; I2 = 9%; P = 0.28) or small for gestational age (RR 0.96, 95% CI: 0.91–1.02; I2 = 0%; P = 0.16) in nulliparous women. Funnel plots indicated that no significant publication bias existed in this meta-analysis. Except for preterm birth at less than 34 weeks of gestation, placental abruption and cesarean section, the sensitivity analysis showed similar results, which confirmed the robustness of this meta-analysis.ConclusionsLow-dose aspirin might reduce the risk of preterm birth at less than 34 weeks of gestation in nulliparous women. The use of low-dose aspirin in nulliparous women increased the risk of postpartum hemorrhage and might increase the risk of placental abruption and cesarean section.

Enhancing marathon safety: The role of low-dose aspirin in cardiac arrest prevention

Enhancing marathon safety: The role of low-dose aspirin in cardiac arrest prevention

Comparison of American College of Cardiology/American Heart Association Cardiovascular Risk Score, Framingham Risk Scores, European Society of Cardiology Cardiovascular Disease Risk Calculator, QRISK3-2018 Risk Calculator in Patients Presenting with First Time with Myocardial Infarction: A Step toward the Development of Indian Cardiac Risk Score

Introduction: One of the primary reasons for fatalities and impairments on a global scale is cardiovascular disease (CVD), encompassing a cluster of illnesses impacting the heart and blood vessels. A CVD risk assessment is a screening tool that measures an individual’s risk of developing CVD. Objective: The objective of this study was to compare and evaluate cardiovascular risk using internationally recognized CVD risk scoring systems. Methodology: A prospective, cross-sectional study was carried out for 2 months after the approval of the ethics committee. Naive myocardial infarction (MI) patients presenting to the cardiology department and conforming to the inclusion criteria were enrolled in the study. Patients who are taking statins or any lipid-lowering drugs, as well as patients who are on low-dose aspirin and antidiabetic medications. Using the aforementioned gathered data, the cardiovascular risk scores were computed employing the American College of Cardiology/American Heart Association (ACC/AHA), Framingham risk scores (FRS), European Society of Cardiology (ESC) – CVD risk calculator, and QRISK→3-2018, and subsequently categorized as low risk, intermediate, or high risk based on the individual risk scores. Results: We enrolled 42 patients, with a mean age of 60 years with male dominance. The mean body mass index was 25.5. With a cholesterol/high-density lipoprotein (HDL) ratio of 4.9, the mean systolic blood pressure/diastolic blood pressure was 126/77 mm of Hg. The mean ACC/AHA cardiovascular risk score for 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 11.34%, FRS mean score was 12%, ESC CVD risk calculator mean score was 15.45%, and QRISK3-2018 risk calculator mean score was 20.87% in patients presenting with first time with MI. Conclusion: QRISK3-2018 risk calculator is the most effective out of all the risk calculators with a maximum detection rate of MI in first time presented patients with Naïve MI patients.

Dual-pathway Inhibition with Low-dose Aspirin and Rivaroxaban versus Aspirin Monotherapy in Patients with Coronary Artery Disease and Peripheral Artery Disease: Systematic Literature Review and Meta-analysis.

Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A systematic literature review and meta-analysis compared the efficacy, safety and net clinical benefit (NCB) of DPI with aspirin. PubMed and Embase were searched for randomised controlled trials reporting clinical efficacy, safety and NCB of DPI compared with aspirin alone in patients with coronary artery disease (CAD) and/or peripheral artery disease. Six articles representing four trials were included. DPI versus aspirin alone significantly reduced major adverse cardiovascular events (HR 0.77; 95% CI [0.69-0.87]; p<0.01), increased International Society on Thrombosis and Haemostasis major bleeding events (HR 1.67; 95% CI [1.37-2.02]; p<0.01) and resulted in a significant NCB (HR 0.79; 95% CI [0.70-0.90]; p<0.01). These results underscore the potential benefit of DPI in patients with CAD, including those in the immediate post-acute coronary syndrome stage and with established CAD, as well as patients with peripheral artery disease.