Body mass index modified the effectiveness of low dose aspirin treatment on frozen-thawed embryo transfer outcome: a propensity score-matched study.

Background: Low-dose aspirin is one of the widely used adjuvants in assisted reproductive technologies with the hope of improving the live birth rate. However, the studies regarding its effects are conflicting. The study aimed to investigate the association between aspirin administration and live birth following frozen-thawed embryo transfer (FET) in patients with different body mass index (BMI). Methods: A retrospective cohort study was performed on 11,993 patients receiving FET treatments. 644 of which received a low-dose aspirin (100 mg/day) during endometrial preparation until 10 weeks after transfer. Propensity score matching was performed to avoid selection biases and potential confounders. Results: The clinical pregnancy rate and live birth rate were similar before matching (54.4% versus 55.4%, RR: 1.02, 95%CI: 0.95-1.09, and 46.3 versus 47.8, RR: 1.03, 95%CI: 0.95-1.12 respectively). A weak association in favor of aspirin administration was found in the matched cohort (49.5% versus 55.4%, RR: 1.12, 95%CI: 1.01-1.24, and 41.9% versus 47.8%, RR: 1.14, 95%CI: 1.01-1.29 respectively). However, when stratified the patients with WHO BMI criteria, a significant increase in live birth rate associated with aspirin treatment was found only in patients with low BMI (<18.5 kg/m2) in either unmatched (46.4% versus 59.8%, RR:1.29, 95%CI:1.07-1.55) or matched cohort (44% versus 59.8%, RR: 1.36, 95%CI: 1.01-1.83) but not in patients with higher BMI categories. With the interaction analysis, less association between aspirin and live birth appeared in patients with normal BMI (Ratio of OR:0.49, 95%CI: 0.29-0.81) and high BMI (Ratio of OR:0.57, 95%CI: 0.27-1.2) compared with patients with low BMI. Conclusion: BMI may be considered when evaluating aspirin's effect in FET cycles.

Development and assessment of immediate-release tablets containing clopidogrel bisulphate & aspirin-strategy for optimizing the combination formulation.

The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination (Clopidogrel bisulphate and Aspirin) tablets. The proposed combination product utilizes Clopidogrel to protect the moisture-sensitive aspirin component, enhancing its stability against atmospheric conditions. Response-surface approach (Design Expert vs. 13) was used to generate this IR tablet by calculating the right composition of independent variables such as Microcrystalline cellulose 102, pregelatinized starch and Hydroxypropyl cellulose. 32 factorial design was used to estimate the effects of these independent variables on the responses of dependent variables (disintegration & friability) and constructed a total of nine (9) formulations. Pre and Post formulation, quality control parameters were investigated as per pharmacopeia. A systematic approach was used for the optimization process and a prototype checkpoint batch (CPB) based on the better contrast of independent variables was prepared. In vitro analysis of formulations was carried out to estimate the responses. Friability was found in the range of 0.088-1.076%w/w, except F1 = 1.076 all are within limits (NMT 1.0%). Disintegration time was recorded 7.3 ± 1.20 as lower and 24.5 ± 1.63 min was the highest. The release of drugs from their dosage form was fast and rapid, for clopidogrel after 15min was 70.42-96.82% with SD ± 8.71 and aspirin was 69.88-91.49% in 15 min with SD ± 6.41, all the tablets were released more than 80% in 20 min. The stability outcomes of CPB tablets after 15 days of stress study (60 ± 2°C and 75 ± 5%) indicated good compatibility and stability of APIs with excipients. It was concluded that the direct compression method can be preferred to prepare a combination product with cost-effectiveness. It was also concluded that the proposed methodology could increase Aspirin's stability and allow for an aqueous coating system to finish the product with a film coating. By using Design Expert software, the best composition of the formulation can be selected and optimized in a short period of time with minimum trial and errors. The results also demonstrated that the use of a fixed-dose combination tablet instead of the individual is expected to be more convenient to patients and thus improves patient compliance and decreases the occurrence of adverse effects and side effects.

An Aspirin-Free Strategy for Immediate Treatment Following Complex Percutaneous Coronary Intervention.

BACKGROUND: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI). OBJECTIVES: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI. METHODS: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. RESULTS: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions. CONCLUSIONS: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111).

Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.

BACKGROUND: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. METHODS: In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. DISCUSSION: Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.

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).

The Ability of Primary Care Practices to Measure and Report on Care Quality.

BACKGROUND: Creating useful clinical quality measure (CQM) reports in a busy primary care practice is known to depend on the capability of the electronic health record (EHR). Two other domains may also contribute: supportive leadership to prioritize the work and commit the necessary resources, and individuals with the necessary health information technology (IT) skills to do so. Here we describe the results of an assessment of the above 3 domains and their associations with successful CQM reporting during an initiative to improve smaller primary care practices' cardiovascular disease CQMs. METHODS: The study took place within an AHRQ EvidenceNOW initiative of external support for smaller practices across Washington, Oregon and Idaho. Practice facilitators who provided this support completed an assessment of the 3 domains previously described for each of their assigned practices. Practices submitted 3 CQMs to the study team: appropriate aspirin prescribing, use of statins when indicated, blood pressure control, and tobacco screening/cessation. RESULTS: Practices with advanced EHR reporting capability were more likely to report 2 or more CQMs. Only one-third of practices were "advanced" in this domain, and this domain had the highest proportion of practices (39.1%) assessed as "basic." The presence of advanced leadership or advanced skills did not appreciably increase the proportion of practices that reported 2 or more CQMs. CONCLUSIONS: Our findings support previous reports of limited EHR reporting capabilities within smaller practices but extend these findings by demonstrating that practices with advanced capabilities in this domain are more likely to produce CQM reports.

Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.

OBJECTIVES: Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function. MATERIALS AND METHODS: We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/µL. RESULTS: Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units. CONCLUSIONS: End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.

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

INTRODUCTION: 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. MATERIALS AND METHODS: 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'. RESULTS: 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'. CONCLUSIONS: 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. TRIAL REGISTRATION: PROSPERO CRD42022359718. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359718.

Low-dose acetylsalicylic acid for the prevention of pre-eclampsia.

Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended prophylactic low-dose acetylsalicylic acid (LDA). If new screening algorithms are implemented, LDA will be recommended to around 10% of pregnant women. The use of LDA may slightly increase the risk of minor bleeding disturbances. Otherwise, there is a lot of promising data regarding the safety of LDA use during pregnancy, as argued in this review.

Impact of low-dose aspirin exposure on obstetrical outcomes: a meta-analysis.

OBJECTIVE: To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs). METHODS: A systematic search of the PubMed, Cochrane Library, Web of Science and Embase databases from inception to January 2024 was conducted to identify studies exploring the role of aspirin on pregnancy, reporting obstetrical-related outcomes, including preterm birth (PTB, gestational age <37 weeks), small for gestational age (SGA), low birth weight (LBW, birthweight < 2500g), perinatal death (PND), admission to the neonatal intensive care unit (NICU), 5-min Apgar score < 7 and placental abruption. Relative risks (RRs) were estimated for the combined outcomes. Subgroup analyses were performed by risk for preeclampsia (PE), LDA dosage (<100 mg vs. ≥100 mg) and timing of onset (≤20 weeks vs. >20 weeks). RESULTS: Forty-seven studies involving 59,124 participants were included. Compared with placebo, LDA had a more significant effect on low-risk events such as SGA, PTB and LBW. Specifically, LDA significantly reduced the risk of SGA (RR = 0.91, 95% CI: 0.87-0.95), PTB (RR = 0.93, 95% CI: 0.89-0.97) and LBW (RR = 0.94, 95% CI: 0.89-0.99). For high-risk events, LDA significantly lowered the risk of NICU admission (RR = 0.93, 95% CI: 0.87-0.99). On the other hand, LDA can significantly increase the risk of placental abruption (RR = 1.72, 95% CI: 1.23-2.43). Subgroup analyses showed that LDA significantly reduced the risk of SGA (RR = 0.86, 95% CI: 0.77-0.97), PTB (RR = 0.93, 95% CI: 0.88-0.98) and PND (RR = 0.65, 95% CI: 0.48-0.88) in pregnant women at high risk of PE, whereas in healthy pregnant women LDA did not significantly improve obstetrical outcomes, but instead significantly increased the risk of placental abruption (RR = 5.56, 95% CI: 1.92-16.11). In pregnant women at high risk of PE, LDA administered at doses ≥100 mg significantly reduced the risk of SGA (RR = 0.77, 95% CI: 0.66-0.91) and PTB (RR = 0.56, 95% CI: 0.32-0.97), but did not have a statistically significant effect on reducing the risk of NICU, PND and LBW. LDA started at ≤20 weeks significantly reduced the risk of SGA (RR = 0.76, 95% CI: 0.65-0.89) and PTB (RR = 0.56, 95% CI: 0.32-0.97). CONCLUSIONS: To sum up, LDA significantly improved neonatal outcomes in pregnant women at high risk of PE without elevating the risk of placental abruption. These findings support LDA's clinical application in pregnant women, although further research is needed to refine dosage and timing recommendations.

Pharmacist-Led Deprescribing of Aspirin in Older People in an Outpatient Setting.

Background In 2019, the American College of Cardiology and American Heart Association updated their joint guidelines stating low-dose aspirin should not be used on a routine basis for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among people older than 70 years of age because of increased bleeding risk.1 In addition to these updated guidelines, a statement released by the US Preventive Services Task Force in April 2022 recommends against the initiation of low-dose aspirin for primary prevention of cardiovascular disease in people 60 years of age or older.² Despite these updated recommendations, aspirin continues to be a common medication older patients take, providing an opportunity for a clinical pharmacist deprescribing intervention. Objective To identify the role of a pharmacist-led aspirin deprescribing intervention within a safety-net health system in the outpatient setting. Methods This project included patients 70 years of age and older who had aspirin listed as an active medication without documented ASCVD. This project assessed aspirin deprescribing rates, time spent on pharmacist outreach, and reasons for patient and/or provider refusal to discontinue aspirin. Results One hundred thirty-one eligible patients were contacted. Of those, 78 (60%) patients discontinued aspirin after speaking with the pharmacist, and 8 patients discontinued aspirin after a clinical pharmacist recommendation to the patient's primary care provider (PCP). The median time spent on outreach was approximately eight minutes. Of the 6 patients who consented to the project but declined to discontinue aspirin therapy based on pharmacist intervention, 5 preferred to discuss the issue with their PCP, while 1 patient was told by an outside provider to take aspirin. Conclusion Results indicate the successful impact a clinical pharmacist may have in deprescribing aspirin in a high-risk population. These data may also suggest that an active and intentional approach to deprescribing is likely to be more effective than a written recommendation to providers.

Evaluation of Aspirin Prescribing and Gastrointestinal Bleeding in Adults 60 Years of Age and Older in a Large, Academic Health System.

Background National guidelines no longer recommend adults 60 years of age and older to begin treatment with low-dose daily aspirin for primary prevention of atherosclerotic cardiovascular disease (CVD) due to a lack of proven net benefit and a higher risk of bleeding. Objective The objective of this cross-sectional retrospective analysis was to evaluate the appropriateness of low-dose aspirin prescribing and subsequent gastrointestinal bleeding in older persons receiving primary care in a large academic health system. Setting Large, academic health system within Colorado. Patients Patients with an active order for daily low-dose aspirin as of July 1, 2021, were assessed for appropriateness based on indication (primary vs secondary prevention) and use of a concomitant proton-pump inhibitor (PPI). Incident gastrointestinal bleeds (GIBs) in the subsequent 12 months and GIB risk factors were also evaluated. Results A total of 19,525 patients were included in the analysis. Eighty-nine percent of patients identified as White and 54% identified as male. Of the total cohort, 44% had CVD and 19% were co-prescribed a PPI. GIB occurred in 247 patients (1.27%) within the subsequent year. Risk factors significantly associated with a GIB within 1 year included: history of GIB, history of peptic ulcer disease, other esophageal issue (esophagitis, Barrett's esophagus, Mallory Weiss tears, etc.), 75 years of age or older, and history of gastroesophageal reflux disease. Conclusion This evaluation found that many older persons at this institution may be inappropriately prescribed aspirin, providing opportunities for pharmacists to improve medication safety by deprescribing aspirin among primary prevention patients or potentially co-prescribing a PPI in secondary prevention patients.

Implementation of a Pharmacist-Driven Aspirin Deprescribing Protocol Among Older Veterans in a Primary Care Setting.

Background Recent cardiovascular guideline updates recommend against the use of aspirin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in older people. However, aspirin use remains common in this population. Objective To implement and evaluate the benefit of a pharmacist-driven aspirin deprescribing protocol compared with primary care provider (PCP) education-only in a primary care setting. Methods This prospective, cohort project targeted deprescribing for patients prescribed aspirin for primary prevention of ASCVD. Patients were included if they received primary care services at the Milwaukee Veterans Health Administration Medical Center (VHA) and were 70 years of age or older. Criteria for exclusion were aspirin obtained outside the VHA system, aspirin prescribed for a non-ASCVD-related condition, and/or a history of ASCVD. Active deprescribing by pharmacists and PCP education took place in the intervention group with PCP education only in the standard-of-care group. The primary outcome was the proportion of patients who had aspirin deprescribed in each group. Secondary outcomes included patient acceptability of the intervention and barriers to implementation. Results A total of 520 patients were prescribed aspirin in the intervention group versus 417 in the education-only group. Sixty-five patients met intervention criteria and were contacted for aspirin deprescribing. The pharmacist-led active deprescribing group led to a higher rate of aspirin deprescriptions versus the education-only group (54% vs 18%; P = 0.0001) for patients who met criteria. Conclusion A pharmacist-led aspirin deprescribing protocol within a primary care setting significantly decreased the number of aspirin prescriptions compared with PCP education only.

Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis: a protocol for an open label, multi-center, parallel arms, randomized controlled superiority trial (INSHORT trial).

BACKGROUND: Despite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM. METHODS: An open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment.  DISCUSSION: Current WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM. TRIAL REGISTRATION: Clinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314 ). CLINICALTRIALS: gov NCT05917340. Registered on 6 August 2023 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT05917340 ). PROTOCOL VERSION: Version 1.3 dated 12 July 2023.

Individualized antiplatelet therapy for non-cardiogenic ischemic stroke.

OBJECTIVE: This research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. METHODS: Among a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. RESULTS: The individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. CONCLUSION: Individualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.

Limb Outcomes With Ticagrelor Plus Aspirin in Patients With Diabetes Mellitus and Atherosclerosis.

BACKGROUND: Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. OBJECTIVES: This study sought to determine the effect of ticagrelor on limb events. METHODS: Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. RESULTS: Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; Pinteraction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (Pinteraction = 0.40) or TIMI major bleeding (Pinteraction = 0.3239). CONCLUSIONS: Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795).

Dose-Dependent Effect of Aspirin Use in Reducing Diabetes-Associated Dementia Risk Among Elderly Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: This study investigated the association between aspirin use and diabetes-associated dementia in older patients with type 2 diabetes mellitus (T2DM), assessing aspirin's potential protective effects, intensity of use, and dose-dependency against dementia. DESIGN: A cohort study evaluating the dose-dependent protective impact of aspirin against dementia in a population-based sample. SETTING AND PARTICIPANTS: Older patients with T2DM (≥60 years), comparing aspirin users with nonusers. METHODS: Used a time-varying Cox hazards model to assess dementia incidence. RESULTS: Older aspirin users exhibited a significant reduction in dementia risk (adjusted hazard ratio [aHR], 0.44; 95% CI, 0.41-0.46). The lowest aHRs for dementia were observed at a daily intensity of 0.91 defined daily doses (DDDs), and higher daily dosages (>0.91 DDD) showed gradually increasing aHRs (although still <1). Analysis of cumulative DDD revealed a dose-response relationship, with progressively lower aHRs across quartiles (0.16, 0.42, 0.57, and 0.63 for quartiles 4, 3, 2, and 1, respectively) compared with never aspirin users (P for trend < .0001). CONCLUSIONS AND IMPLICATIONS: Aspirin use in older patients with T2DM significantly reduces dementia risk. The optimal daily intensity of aspirin use (0.91 DDD) is associated with the lowest aHR for dementia. These findings suggest a dose-dependent relationship, supporting the potential benefits of higher cumulative dosages of aspirin in reducing dementia risk in this population.