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JAMA Jun 2023Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown.
OBJECTIVE
To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022.
INTERVENTIONS
Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase.
MAIN OUTCOMES AND MEASURES
The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days.
RESULTS
Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group.
CONCLUSIONS AND RELEVANCE
Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03661411.
Topics: Female; Humans; Male; Middle Aged; Cerebral Hemorrhage; Fibrinolytic Agents; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Tissue Plasminogen Activator; Treatment Outcome; Drug Therapy, Combination; Thrombolytic Therapy; Administration, Intravenous; Clopidogrel; Aspirin; Follow-Up Studies; Aged; Recovery of Function
PubMed: 37367978
DOI: 10.1001/jama.2023.7827 -
JAMA Network Open Jul 2023Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals.
OBJECTIVE
To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin.
DESIGN, SETTING, AND PARTICIPANTS
This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.
INTERVENTIONS
Daily 100-mg enteric-coated aspirin or matching placebo.
MAIN OUTCOMES AND MEASURES
Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records.
RESULTS
Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04).
CONCLUSIONS AND RELEVANCE
This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma.
TRIAL REGISTRATION
ISRCTN.org Identifier: ISRCTN83772183.
Topics: Female; Humans; Aged; Platelet Aggregation Inhibitors; Aspirin; Stroke; Cerebral Hemorrhage; Intracranial Hemorrhages; Ischemic Stroke
PubMed: 37494038
DOI: 10.1001/jamanetworkopen.2023.25803 -
Annals of Medicine Dec 2023Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition... (Review)
Review
Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition site of GP IIb/IIIa to prevent platelet aggregation. It reduces the incidence of thrombotic cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Although generally considered safe, tirofiban has been reported to be associated with thrombocytopenia in several case reports and clinical trials. The pathogenesis for this adverse reaction is not entirely understood, is thought to be due to immune-mediated reaction. This side effect caused by tirofiban is especially concerning given how frequently it is used in the practice of contemporary cardiovascular care. The present review provides an overview of the pathophysiology, clinical presentation, management, and risk factors associated with tirofiban-induced thrombocytopenia.
Topics: Humans; Tirofiban; Platelet Aggregation Inhibitors; Tyrosine; Thrombocytopenia; Platelet Glycoprotein GPIIb-IIIa Complex; Acute Coronary Syndrome
PubMed: 37439782
DOI: 10.1080/07853890.2023.2233425 -
Frontiers in Molecular Biosciences 2023Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the... (Review)
Review
Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating thrombosis, modulating key pathways including endothelial activation, platelet aggregation, and coagulation. Furthermore, SIRT1 displays anti-inflammatory activity both , and in clinical studies, particularly via the reduction of oxidative stress. On these bases, several studies have investigated the therapeutic potential of targeting SIRT1 for the prevention of thrombosis. This review provides a comprehensive and critical overview of the main preclinical and clinical studies and of the current understanding of the role of SIRT1 in thrombosis.
PubMed: 38304233
DOI: 10.3389/fmolb.2023.1325002 -
Journal of Community Hospital Internal... 2023Myocarditis and pericarditis are rare adverse reactions, more commonly seen in young males after receiving the second dose of an mRNA vaccine. However, the benefits of...
Myocarditis and pericarditis are rare adverse reactions, more commonly seen in young males after receiving the second dose of an mRNA vaccine. However, the benefits of vaccination heavily outweigh the risk of these side effects. In addition, vaccination boosters are effective against the newest, more infective variants. Therefore we expect more vaccines to be administered in the following years. The objective of this study is to review the current understanding of the mechanism, diagnosis, and treatment of myocarditis and pericarditis. Proposed mechanisms include molecular mimicry against the S protein and hypersensitivity reactions with mRNA vaccines and platelet aggregation and thrombus formation in cardiac blood vessels with adenoviral vaccines. Diagnosis of myocarditis is based on clinical findings, cardiac enzymes, ECG, MRI, and echocardiographic findings. Management includes NSAIDs and cardiovascular support in selected cases with ventricular dysfunction. Most patients have a mild presentation with preservation of cardiac function and recover entirely within seven days; the average hospital stay is three days. Long-term complications are infrequent.
PubMed: 37868673
DOI: 10.55729/2000-9666.1229