Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

Low-dose aspirin prophylaxis to prevent hypertensive disorders of pregnancy after in vitro fertilisation: a scoping review protocol.

INTRODUCTION: Pregnancies resulting from in vitro fertilisation are associated with an increased risk of developing hypertensive disorders of pregnancy, such as preeclampsia, when compared with naturally conceived pregnancies. OBJECTIVE: The efficacy of aspirin prophylaxis to reduce the incidence of preeclampsia is well established in naturally conceived pregnancies identified as high risk for developing preeclampsia. However, the efficacy of aspirin to reduce the rate of preeclampsia for all pregnancies resulting from in vitro fertilisation remains uncertain, although in vitro fertilisation conception is a well-known risk factor for preeclampsia. Therefore, the purpose of this scoping review is to provide a comprehensive overview of the current literature regarding the use of low-dose aspirin to prevent hypertensive disorders of pregnancy after in vitro fertilisation. INCLUSION CRITERIA: This review will identify all peer-reviewed published articles including pregnant women who underwent embryo transfer after in vitro fertilisation and were prescribed low-dose aspirin to reduce the risk of hypertensive disorders of pregnancy. METHODS: We have devised a comprehensive search strategy to systematically identify pertinent studies published from January 2000 until May 2024, within the Medline (PubMed interface), Embase and Scopus databases. The search strategy is based on the keywords 'aspirin,' 'pregnancy-induced hypertension,' and ('in vitro fertilization' OR 'oocyte donation' OR 'embryo transfer' OR 'donor conception'). Two reviewers will independently screen the titles, abstracts and full-text articles to select the relevant articles, using the Covidence software. ETHICS AND DISSEMINATION: No patients are involved in this study. This study aims to be published in a peer-reviewed journal and could be presented at a conference.

Timing of P2Y12 Inhibitor Administration in Patients With STEMI Undergoing Primary PCI.

BACKGROUND: The optimal timing of P2Y12 inhibitor administration in patients with ST-segment elevation myocardial infarction (STEMI) has not been completely elucidating. OBJECTIVES: This analysis from a prospective multicenter registry sought to assess the safety and effectiveness of P2Y12 inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PCI) within a regional STEMI network. METHODS: Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y12 inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis. RESULTS: Of 1,624 patients included, 1,033 received P2Y12 inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non-pretreated cohort more often had history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y12 inhibitors predicted lower risk of MACE (adjusted HR: 0.53; 95% CI: 0.37-0.76), without increasing bleeding risk (adjusted HR: 0.62; 95% CI: 0.36-1.05), resulting in superior net clinical benefit (adjusted HR: 0.47; 95% CI: 0.26-0.86) compared with in-cath lab administration of P2Y12 inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y12 inhibitor administration and PCI was longer than 80 minutes. CONCLUSIONS: In contemporary patients with STEMI transferred for primary PCI, pretreatment with P2Y12 inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.

Clinical outcomes of adjusted-dose versus standard-dose prasugrel in East Asian patients with acute myocardial infarction.

BACKGROUND: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI. METHODS: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups. RESULTS: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000). CONCLUSIONS: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE.

Abbreviated Versus Standard Dual Antiplatelet Therapy Times After Percutaneous Coronary Intervention in Patients With High Bleeding Risk With Acute Coronary Syndrome: Insights From the SWEDEHEART Registry.

BACKGROUND: Dual antiplatelet therapy (DAPT) reduces ischemic events but increases bleeding risk, especially in patients with high bleeding risk (HBR). This study aimed to compare outcomes of abbreviated versus standard DAPT strategies in patients with HBR with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS AND RESULTS: Patients from the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-Based Bare in Heart Disease Evaluated According to Recommended Therapies) registry with at least 1 HBR criterion who underwent percutaneous coronary intervention for acute coronary syndrome were identified and included. Patients were divided into 2 groups based on their planned DAPT time at discharge: 12-month DAPT or an abbreviated DAPT strategy and matched according to their prescribed P2Y12 inhibitor at discharge. The primary outcome assessed was time to net adverse clinical events at 1 year, which encompassed cardiac death, myocardial infarction, ischemic stroke, or clinically significant bleeding. Time to major adverse cardiovascular events and the individual components of net adverse clinical events were considered secondary end points. A total of 4583 patients were included in each group. The most frequently met HBR criteria was age older than 75 years (65.6%) and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy score ≥25 (44.6%) in the standard DAPT group and oral anticoagulant therapy (79.6%) and age 75 years and older (55.2%) in the abbreviated DAPT group. There was no statistically significant difference in net adverse clinical events (12.9% versus 13.1%; hazard ratio [HR], 0.99 [95% CI, 0.88-1.11], P=0.83), major adverse cardiovascular events (8.6% versus 7.9%; HR, 1.08 [95% CI, 0.94-1.25]), or their components between groups. The results were consistent among all of the investigated subgroups. CONCLUSIONS: In patients with HBR undergoing percutaneous coronary intervention due to acute coronary syndrome, abbreviated DAPT was associated with comparable rates of net adverse clinical events and major adverse cardiovascular events to a DAPT duration of 12 months.

Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy Study: A Knowledge, Attitude, and Practice Study among Indian Interventional Cardiologists.

BACKGROUND: Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug management of CAD, including optimizing the duration of antiplatelet treatment regimens in the management of CAD, which is an intricate clinical issue. The available evidence indicates that East Asians have a higher bleeding risk. However, the Indian phenotype differs from that of East Asians, making this data confounding when applied to clinical decision-making among Indian patients. There is a need for a close understanding of Indian interventional cardiologists' perceptions of complex decision-making pertaining to antiplatelet agents among Indian CAD patients in real-world clinical settings. AIM: This Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy (INDEPTH) study aims to assess the perspective of Indian interventional cardiologists regarding de-escalating from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), approach to decision-making, barriers, and related challenges in CAD management. METHODS: A cross-sectional knowledge, attitude, and practice (KAP) study survey was carried out among Indian interventional cardiologists practicing across different regions of India. A total of 209 responses were received. Descriptive statistics was used to summarize all the parameters. IBM Statistical Package for the Social Sciences (SPSS) statistics was used for biostatistical analysis. RESULTS: The study indicated that >90% of CAD patients received DAPT therapy immediately after percutaneous coronary intervention (PCI) (86.1%, p < 0.001). About 115 (55%) of the respondents reported using calculator-based scoring for evaluating bleeding risk in patients on DAPT therapy for the management of acute coronary syndrome (ACS) with post-PCI (p = 0.167). Regarding the usual duration of DAPT therapy post-ACS, nearly half of the respondents, 94 (45%), said that 6-12 months is the usual duration for DAPT therapy in post-ACS patients, followed by > 12 months 94 (45%) of the respondents; 17 (8.1%) of the respondents reported it is 3-6 months, and lastly up to 3 months as per four (1.9%) of the respondents (p < 0.001). A total of 128 (61%) of the respondents strongly believe that balancing bleeding with ischemic risk influenced the choice of antiplatelet agent when treating established CAD. As per interventional cardiologists surveyed, the perfect de-escalation time frame for Indian CAD patients with high bleeding risk (HBR) is up to 3 months (35.9%, p < 0.001), 6-12 months for medium bleeding risk (48.8%, p < 0.001), and >12 months for low bleeding risk (65.6%, p < 0.001). Regarding SAPT therapy, almost one-third of the respondents, 65 (31.1%), reported that they prescribed antiplatelet therapy other than aspirin in 20-40% of their SAPT-eligible patients. Furthermore, 69 (33%) of the respondents said that they preferred to prescribe clopidogrel in 50-75% of SAPT-eligible patients. While 64 (30.5%) prescribed in 25-50%, 53 (25.4%) prescribed in <25% and 23 (11%) of the respondents prescribed the drug in >75% of the SAPT-eligible patients. (p < 0.001). "Atorvastatin + clopidogrel" is the most preferred combination of SAPT primarily for the management of CAD among the majority of interventional cardiologists [33%, 95% confidence interval (CI): 1.97-2.24, p < 0.001]. The study respondents also indicated a need for Indian-specific guidelines on de-escalating from DAPT to SAPT in CAD management. CONCLUSION: The INDEPTH study indicated that the majority of CAD patients received DAPT immediately after PCI. The perfect de-escalation time frame for Indian CAD patients with "high-bleeding" risk is up to 3 and 6-12 months for "medium-bleeding" risk and >12 months for "low-bleeding" risk. One-third of respondents used clopidogrel as an antiplatelet agent in 50-75% of SAPT-eligible patients. Atorvastatin + clopidogrel is predominantly the most preferred combination of statin + SAPT for the management of CAD. Although the current international guidelines cover the Indian perspective to some extent, there is a need for Indian-specific guidelines on de-escalating from DAPT to SAPT.

Association of CYP2C19 genotypes with postoperative atrial fibrillation after coronary artery bypass surgery.

This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.

Assessing the Impact of Morphine on Adverse Outcomes in ACS Patients Treated with P2Y12 Inhibitors: Insights from Multiple Real-World Evidence.

Purpose: Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators. Patients and Methods: Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis. Results: Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42-5.28, false discovery rate adjusted-P =3.55*10-209). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI. Conclusion: The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.

Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage.

Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.

The safety of perioperative antiplatelet continuation without selection biases in microsurgical decompression surgery for single level lumbar spinal stenosis and lumbar disc herniotomy.

PURPOSE: Each institution or physician has to decide on an individual basis whether to continue or discontinue antiplatelet (AP) therapy before spinal surgery. The purpose of this study was to determine if perioperative AP continuation is safe during single-level microsurgical decompression (MSD) for treating lumbar spinal stenosis (LSS) and lumbar disc hernia (LDH) without selection bias. METHODS: Patients who underwent single-level MSD for LSS and LDH between April 2018 to December 2022 at our institute were included in this retrospective study. We collected data regarding baseline characteristics, medical history/comorbidities, epidural hematoma (EDH) volume, reoperation for EDH, differences between preoperative and one-day postoperative blood cell counts (ΔRBC), hemoglobin (ΔHGB), and hematocrits (ΔHCT), and perioperative thromboembolic complications. Patients were divided into two groups: the AP continuation group received AP treatment before surgery and the control group did not receive antiplatelet medication before surgery. Propensity scores for receiving AP agents were calculated, with one-to-one matching of estimated propensity scores to adjust for patient baseline characteristics and past histories. Reoperation for EDH, EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complications were compared between the groups. RESULTS: The 303 enrolled patients included 41 patients in the AP continuation group. After propensity score matching, the rate of reoperation for EDH, the EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complication rates were not significantly different between the groups. CONCLUSION: Perioperative AP continuation is safe for single-level lumbar MSD, even without biases.

WITHDRAWN: Use of proton pump inhibitors (PPI) in patients with acute coronary syndrome (ACS) receiving dual-antiplatelet therapy (DAPT).

 : This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been withdrawn at the request of the authors, editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.

Antiplatelet therapy after coronary artery bypass surgery: five year follow-up of randomised DACAB trial.

OBJECTIVE: To assess the effect of different antiplatelet strategies on clinical outcomes after coronary artery bypass grafting. DESIGN: Five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting (DACAB) trial. SETTING: Six tertiary hospitals in China; enrolment between July 2014 and November 2015; completion of five year follow-up from August 2019 to June 2021. PARTICIPANTS: 500 patients aged 18-80 years (including 91 (18.2%) women) who had elective coronary artery bypass grafting surgery and completed the DACAB trial. INTERVENTIONS: Patients were randomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166) for one year after surgery. After the first year, antiplatelet therapy was prescribed according to standard of care by treating physicians. MAIN OUTCOME MEASURES: The primary outcome was major adverse cardiovascular events (a composite of all cause death, myocardial infarction, stroke, and coronary revascularisation), analysed using the intention-to-treat principle. Time-to-event analysis was used to compare the risk between treatment groups. Multiple post hoc sensitivity analyses examined the robustness of the findings. RESULTS: Follow-up at five years for major adverse cardiovascular events was completed for 477 (95.4%) of 500 patients; 148 patients had major adverse cardiovascular events, including 39 in the dual antiplatelet therapy group, 54 in the ticagrelor monotherapy group, and 55 in the aspirin monotherapy group. Risk of major adverse cardiovascular events at five years was significantly lower with dual antiplatelet therapy versus aspirin monotherapy (22.6% v 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04) and versus ticagrelor monotherapy (22.6% v 32.9%; 0.66, 0.44 to 1.00; P=0.05). Results were consistent in all sensitivity analyses. CONCLUSIONS: Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy. TRIAL REGISTRATION: NCT03987373ClinicalTrials.gov NCT03987373.

Variability patterns in dual antiplatelet therapy following endovascular repair of intracranial aneurysms: Insight into regimen heterogeneity and the need for a consensus.

This comprehensive review delves into the evolving field of neurointervention for intracranial aneurysms, exploring the critical adjunct of Dual Antiplatelet Therapy (DAPT) to endovascular coiling, stent-assisted coiling (SAC), flow-diversion stents, and flow-disruption (intrasaccular) devices. Despite growing evidence supporting the success of DAPT in reducing thromboembolic events, the lack of consensus on optimal regimens, doses, and duration is evident. Factors contributing to this variability include genetic polymorphisms affecting treatment response and ongoing debates regarding the clinical significance of hemorrhagic complications associated with DAPT. This review analyzes pre- and post-procedural antiplatelet usage across various interventions. The imperative lies in ongoing research to define optimal DAPT durations, ensuring a nuanced approach to the delicate balance between thrombosis and hemorrhage in intracranial aneurysm management.

Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis.

Importance: Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH. Objective: To determine the associated risk of sICH in patients taking prestroke dual antiplatelet therapy receiving alteplase for acute ischemic stroke using propensity score matching analysis. Design, Setting, and Participants: This cohort study used data from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke (GWTG-Stroke) registry between 2013 and 2021. Data were obtained from hospitals in the GWTG-Stroke registry. This study included patients hospitalized with acute ischemic stroke and treated with IV-tPA. Data were analyzed from January 2013 to December 2021. Exposures: Prestroke DAPT before treatment with IV-tPA for acute ischemic stroke. Main Outcome Measures: sICH, In-hospital death, discharge modified Rankin scale score, and other life-threatening systemic hemorrhages. Results: Of 409 673 participants, 321 819 patients (mean [SD] age, 68.6 [15.1] years; 164 587 female [51.1%]) who were hospitalized with acute ischemic stroke and treated with IV-tPA were included in the analysis. The rate of sICH was 2.9% (5200 of 182 344), 3.8% (4457 of 117 670), and 4.1% (893 of 21 805) among patients treated with no antiplatelet therapy, single antiplatelet therapy (SAPT), and DAPT, respectively (P < .001). In adjusted analyses after propensity score subclassification, both SAPT (odds ratio [OR], 1.13; 95% CI, 1.07-1.19) and DAPT (OR, 1.28; 95% CI, 1.14-1.42) were associated with increased risks of sICH. Prestroke antiplatelet medications were associated with lower odds of discharge mRS score of 2 or less compared with no medication (SAPT OR, 0.92; 95% CI, 0.90-0.95; DAPT OR, 0.94; 95% CI, 0.88-0.98). Results of a subgroup analysis of patients taking DAPT exposed to aspirin-clopidogrel vs aspirin-ticagrelor combination therapy were not significant (OR, 1.35; 95% CI, 0.84-1.86). Conclusions and Relevance: Prestroke DAPT was associated with a significantly elevated risk of sICH among patients with ischemic stroke who were treated with thrombolysis; however, the absolute increase in risk was small. Patients exposed to antiplatelet medications did not have excess sICH compared with landmark trials, which demonstrated overall clinical benefit of thrombolysis therapy for acute ischemic stroke.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial.

Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.