Analysis of Risk of Bleeding Complications After Different Doses of Aspirin in 192,036 Patients Enrolled in 31 Randomized Controlled Trials

doi:10.1016/j.amjcard.2005.01.049

The American Journal of Cardiology

Volume 95, Issue 10, 15 May 2005, Pages 1218-1222

https://doi.org/10.1016/j.amjcard.2005.01.049 Get rights and content

We sought to compare the risk of hemorrhage due to the low (<100 mg), moderate (100 to 200 mg), and high (>200 mg) doses of aspirin (acetylsalicylic acid [ASA]) in 192,036 patients enrolled in 31 clinical trials. Despite substantial differences in the reporting patterns of bleeding complications, low-dose ASA was associated with the lowest risk, and moderate doses caused a relatively high hemorrhagic event rate, especially with regard to minor, gastrointestinal, and total bleeding, and stroke. These findings should be considered when using combination antiplatelets, anticoagulant therapy, or both, with ASA, especially with the daily dose of >100 mg.

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Cited by (304)

The impact of pre-stroke aspirin exposure on radiographic appearance and disability outcomes: A post-hoc analysis of the SPS3 trial: Aspirin Use and Small Subcortical Stroke
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The effect of pre-stroke use of aspirin on small subcortical infarct dimensions or outcomes is not well described. We aimed to bridge this knowledge gap amongst a well-described and heterogeneous patient population.
We performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Stroke (SPS3) trial. The primary exposure was aspirin use ≤7 days of index stroke. The primary outcomes were infarct dimensions. Functional outcomes by modified Rankin Scale (mRS) was a secondary outcome. Age restricted (≥55 years) subgroup analyses were performed as a sensitivity analysis. Descriptive statistical and regression modeling were performed for data analysis.
We included 1423 participants of which 453(31.8 %) used aspirin. Aspirin use was associated with more cardiovascular risk diagnoses. Maximal infarct diameter did not differ with pre-stroke aspirin use (11.3±4.2 mm versus 11.8±4.1 mm, p=0.057) however infarct area was smaller with exposure (126.4±90.0 mm² versus 137.4±97.0 mm², p=0.037) regardless of aspirin strength. Participants ≥55 years had smaller infarct diameters (11.1±4.2 mm versus 11.9±4.4 mm, p=0.019) and area (123.4±87.1 mm² versus 130.6±93.2 mm², p=0.037) with aspirin use. mRS did not significantly differ in our analyses.
In this post-hoc analysis of the SPS3 trial, pre-stroke aspirin use was associated with a smaller infarct area regardless of aspirin strength and without impact on functional outcomes. These findings were more pronounced in participants ≥55 years.
https://clinicaltrials.gov/study/NCT00059306?term= %22sps3 %22&rank=1
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Adherence to European guidelines for the use of aspirin in primary health care
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Cardiovascular disease remains a leading cause of global morbidity and mortality. The administration of low doses of aspirin in secondary prevention of atherosclerotic cardiovascular disease (ASCVD) has been clearly established. However, the most recent guidelines do not recommend aspirin in primary prevention, reserving it for high-risk patients and after a risk/benefit assessment. The aim of this study was to assess adherence to European guidelines for the use of aspirin in primary and secondary prevention of ASCVD in primary health care.
The study population consisted of individuals aged >50 years registered at two primary health care units without (primary prevention) and with previous ASCVD events (secondary prevention).
We studied a total of 1262 individuals, 720 in primary prevention and 542 in secondary prevention. A total of 61 individuals (8.5%) were under aspirin therapy in primary prevention, most of them taking 150 mg/day (57%). In secondary prevention, 195 patients (27%) were receiving aspirin only, most taking 150 mg/day (52%), and 166 patients (31%) were not under any antithrombotic or anticoagulant therapy. The 100 mg dosage was predominant in patients with ischemic heart disease with (64%) and without (64%) angina, as well as those with myocardial infarction (61.5%) and peripheral vascular disease (62%).
In this study, the prevalence of aspirin use in primary prevention was 8.5%. We found that 30% of patients were not taking either antithrombotic or anticoagulation therapy in secondary prevention. In both primary and secondary prevention, the 150 mg dosage was predominant.
As doenças cardiovasculares permanecem uma das principais causas de morbilidade e mortalidade em nível mundial. A administração de baixas doses de ácido acetilsalicílico (AAS) na prevenção secundária de doença cardiovascular aterosclerótica (DCVA) foi claramente estabelecida. Concomitantemente, as recomendações mais recentes não o aconselham na prevenção primária, propondo ser reservado para doentes de alto risco e após uma avaliação risco/benefício. O objetivo deste estudo foi avaliar a adesão às recomendações europeias para o uso de AAS na prevenção primária e secundária de DCVA nos cuidados de saúde primários.
A população em estudo correspondeu a indivíduos >50 anos registados em duas unidades de cuidados de saúde primários sem (prevenção primária) e com eventos de DCVA anteriores (prevenção secundária).
Foram estudados 1262 indivíduos, 720 em prevenção primária e 542 em prevenção secundária. Verificámos que 61 dos indivíduos (8,5%) estavam sob terapia com AAS em prevenção primária, com uma predominância da dose de 150 mg (57%). Em prevenção secundária, 195 dos doentes (27%) estavam a realizar ASA exclusivamente, com uma predominância da dose de 150 mg (52%) e 166 dos doentes (31%) não estavam sob qualquer agente antitrombótico ou anticoagulante. A dosagem de 100 mg foi predominante em doentes com doença cardíaca isquémica com (64%) e sem (64%) angina, enfarte agudo do miocárdio (61,5%) e doença vascular periférica (62%).
Neste estudo, a prevalência do uso de AAS na prevenção primária foi de 8,5%. Identificámos 30% de doentes que não cumpriam terapia antitrombótica ou anticoagulante em prevenção secundária. Quer em prevenção primária como secundária, o uso da dosagem de 150 mg foi predominante.
Clinical outcomes of left atrial appendage occlusion versus direct oral anticoagulation in patients with atrial fibrillation and prior ischemic stroke: A propensity-score matched study
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Citation Excerpt :
The risk of extracranial hemorrhage was, however, increased with DOAC therapy in the randomized trials comparing it to warfarin [3–5]. The AVERROES trial indicated similar major bleeding rates with aspirin and apixaban, however, on-treatment analysis indicated lower risk with aspirin [25] and it appears evident that higher aspirin doses are associated with a higher bleeding risk [26,27]. Most LAAO-centers use a low-dose of aspirin 75–81 mg/daily after LAAO and may explain the lower observed bleeding risk.
This propensity-score matched study investigated clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulation (DOAC) in patients with AF and prior ischemic stroke.
AF patients enrolled in the Amulet Observational Study with a history of ischemic stroke and successful LAAO (n = 299) were compared with a propensity-score matched cohort of incident AF patients with prior ischemic stroke and treated by DOAC (n = 301). The control cohort was identified through the Danish National Patient Registries. Propensity score matching was based on covariates of the CHA₂DS₂-VASc and HAS-BLED scores, with a 1:2 ratio and using Greedy 5:1 digit matching with replacement. The analysis included 2-years follow-up, with a primary composite outcome of ischemic stroke, major bleeding (BARC ≥ 3) or all-cause mortality.
Mean (SD) CHA₂DS₂-VASc scores were 5.26 (1.42) and 5.40 (1.31) and HAS-BLED scores were 3.95 (0.91) and 4.03 (0.96), for the LAAO and DOAC group, respectively.
Total number of primary composite outcome events were 61 (12.4 events/100 patient-years) and 117 (26.9 events/100 patient-years) in the LAAO and DOAC group, respectively. Risk of the primary composite outcome was significantly lower in the LAAO group, hazard rate ratio [HR] 0.48 (95% CI: 0.35–0.65).
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This study indicated significantly lower risk of the composite outcome of stroke, major bleeding and all-cause mortality with LAAO therapy compared to DOAC, in patients with AF and prior stroke. The stroke prevention effectiveness appeared similar, with a significantly lower risk of major bleeding events with LAAO. The suggested clinical benefit of LAAO over DOAC require confirmation in the ongoing randomized OCCLUSION-AF trial.
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Platelet aggregation and thrombus formation represent the basic mechanism for clinical, electrocardiographic, and biomarker changes consistent with acute coronary syndrome. Various oral and intravenous formulations of platelet function inhibitors have been developed to help decrease platelet aggregation due to acute atherosclerotic plaque rupture. In this article, we review the various mechanisms, pharmacokinetics/pharmacodynamics, and the key clinical trials related to the platelet inhibitors that form the basis for current recommendations of their use in the ST elevation myocardial infarction guidelines by the American College of Cardiology/American Heart Association.
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The guideline for coronary artery revascularization replaces the 2011 coronary artery bypass graft surgery and the 2011 and 2015 percutaneous coronary intervention guidelines, providing a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization as well as the supporting documentation to encourage their use.
A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered.
Coronary artery disease remains a leading cause of morbidity and mortality globally. Coronary revascularization is an important therapeutic option when managing patients with coronary artery disease. The 2021 coronary artery revascularization guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with coronary artery disease who are being considered for coronary revascularization, with the intent to improve quality of care and align with patients’ interests.

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^⁎: Drs. Serebruany and Topol are consultants for McNeil Consumer & Specialty Pharmaceuticals. This study was not funded by McNeil.

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Brief reportAnalysis of Risk of Bleeding Complications After Different Doses of Aspirin in 192,036 Patients Enrolled in 31 Randomized Controlled Trials

J Am Coll Cardiol

J Neurol Sci

Lancet

Lancet

Lancet

J Am Coll Cardiol

Risk of bleeding complications with antiplatelet agents: a meta-analysis of 338,191 patients enrolled in 50 randomized controlled trials

Am J Hematol

Effect of clopidogrel in addition to aspirin in patients with acute coronary syndrome without ST-segment elevation

N Engl J Med

Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study

Circulation

Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease

Circulation

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

BMJ

An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction

N Engl J Med

A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke

N Engl J Med

Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk

Lancet

Swedish Aspirin Low-dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events

Lancet

Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice

Lancet

Randomized trial of aspirin, sibrafiban, or both for secondary prevention after acute coronary syndromes

Circulation

Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomized trial

Lancet

Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial

Lancet

Brief report
Analysis of Risk of Bleeding Complications After Different Doses of Aspirin in 192,036 Patients Enrolled in 31 Randomized Controlled Trials