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

Baigent, Colin; Sudlow, Cathie; Collins, Rory; Pető, Richárd; Collaborat, Antithromboci Trialists

doi:10.1136/bmj.324.7329.71

Cited by 5,941 publications

(947 citation statements)

References 47 publications

Supporting

Mentioning

879

Contrasting

Unclassified

Order By: Relevance

“…Here, we report for the first time that many oxylipid CYP products (the LA‐derived 9,10 EpOME and 12,13 DiHOME and the AA‐derived 5,6 DiHETrE and 11‐12 DiHETrE) differ between sexes. The CYP2J and 2C families are responsible for the synthesis of these molecules,6, 7, 35 and sex differences in human CYP activity has been extensively reported 8, 36. We also observed higher levels of 5‐LOX products (namely, the eicosapentaenoic acid–derived 5S‐HEPE, the LA‐derived 9‐HODE, the AA‐derived 5‐HETE, and the α‐linolenic acid–derived 9‐HOTrE) in women.…”

Section: Discussionsupporting

confidence: 59%

“…Understanding these non‐COX‐1‐mediated mechanisms is critical in order to better understand the wide interindividual variability observed in aspirin response. Though aspirin use significantly reduces the risk of cardiovascular death, still ≈25% of high‐risk patients on aspirin therapy show persistent platelet reactivity6, 7 (ie, laboratory aspirin resistance) and atherothrombotic events (ie, clinical aspirin resistance) remain relatively common8 in patients on aspirin therapy. The mechanisms underlying variability in aspirin response are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

View full text Add to dashboard Cite

BackgroundWhile aspirin is a well‐established and generally effective anti‐platelet agent, considerable inter‐individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response.Methods and ResultsWe used a mass‐spectrometry‐based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (−19%, P=1.3×10−5), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid‐derived oxylipids were not significantly associated with arachidonic‐induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen.ConclusionsTogether, these results suggest that linoleic acid‐derived oxylipids may contribute to the non‐COX1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

View full text Add to dashboard Cite

show abstract

“…Therefore, when older patients receive a dual loading dose of antiplatelet therapy after having ACS, they might be at the highest risk of bleeding. In addition, few studies evaluated the effectiveness and safety of a dual loading dose of antiplatelet therapy 1, 16, 17. Most of the recommendations in the guidelines for loading doses of aspirin and a P2Y 12 receptor inhibitor as early as possible or at the time of PCI were mostly based on observational data and experts' opinions, as no randomized controlled trials are available to inform this strategy 2, 3, 4, 5.…”

Section: Discussionmentioning

confidence: 99%

In‐Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) Project

Zhao

Zhou

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundElderly patients with acute coronary syndrome (ACS) are at high risk for ischemic and bleeding events. This study aimed to evaluate the clinical effectiveness and safety of dual loading antiplatelet therapy for patients 75 years and older undergoing percutaneous coronary intervention for ACS.Methods and ResultsThe Improving Care for Cardiovascular Disease in China‐ACS project was a collaborative study of the American Heart Association and Chinese Society of Cardiology. A total of 5887 patients 75 years and older with ACS who had percutaneous coronary intervention and received dual antiplatelet therapy with aspirin and P2Y12 inhibitors (clopidogrel or ticagrelor) between November 2014 and June 2017 were enrolled. The primary effectiveness and safety outcomes were in‐hospital major adverse cardiovascular events and major bleeding. Hazard ratios (HRs) of in‐hospital outcomes with different loading statuses of antiplatelet therapy were estimated using Cox proportional hazard models with multivariate adjustment. A propensity score–matched analysis was also conducted. Compared with patients receiving a dual nonloading dose, patients taking a dual loading dose had increased risks of both major adverse cardiovascular events (HR, 1.66, 95% confidence interval, 1.13–2.44; [P=0.010]) and major bleeding (HR, 2.34, 95% confidence interval, 1.75–3.13; [P<0.001]). Among 3284 propensity score–matched patients, a dual loading dose was associated with a 1.36‐fold risk of major adverse cardiovascular events (HR, 1.36; 95% confidence interval, 0.88–2.11 [P=0.168]) and a 2.08‐fold risk of major bleeding (HR, 2.08; 95% confidence interval, 1.47–2.93 [P<0.001]).ConclusionsA dual loading dose of antiplatelet therapy was associated with increased major bleeding risk but not with decreased major adverse cardiovascular events risk among patients 75 years and older undergoing percutaneous coronary intervention for ACS in China.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02306616.

show abstract

“…Prevention is the key to reducing this burden. Aspirin provides effective ischemic stroke prevention in select patients in both primary and secondary prevention 3, 4, 5, 6. The US Preventive Services Task Force4 recommends aspirin as the only antithrombotic with sufficient evidence for use in primary prevention in high‐risk populations without atrial fibrillation (AF).…”

Section: Introductionmentioning

confidence: 99%

Using Large‐Scale Linkage Data to Evaluate the Effectiveness of a National Educational Program on Antithrombotic Prescribing and Associated Stroke Prevention in Primary Care

Liu¹,

Moorin

Worthington

et al. 2016

JAHA

View full text Add to dashboard Cite

BackgroundThe National Prescribing Service (NPS) MedicineWise Stroke Prevention Program, which was implemented nationally in 2009–2010 in Australia, sought to improve antithrombotic prescribing in stroke prevention using dedicated interventions that target general practitioners. This study evaluated the impact of the NPS MedicineWise Stroke Prevention Program on antithrombotic prescribing and primary stroke hospitalizations.Method and ResultsThis population‐based time series study used administrative health data linked to 45 and Up Study participants with a high risk of cardiovascular disease (CVD) to assess the possible impact of the NPS MedicineWise program on first‐time aspirin prescriptions and primary stroke‐related hospitalizations. Time series analysis showed that the NPS MedicineWise program was significantly associated with increased first‐time prescribing of aspirin (P=0.03) and decreased hospitalizations for primary ischemic stroke (P=0.03) in the at‐risk study population (n=90 023). First‐time aspirin prescription was correlated with a reduction in the rate of hospitalization for primary stroke (P=0.02). Following intervention, the number of first‐time aspirin prescriptions increased by 19.8% (95% confidence interval, 1.6–38.0), while the number of first‐time stroke hospitalizations decreased by 17.3% (95% confidence interval, 1.8–30.0).ConclusionsConsistent with NPS MedicineWise program messages for the high‐risk CVD population, the NPS MedicineWise Stroke Prevention Program (2009) was associated with increased initiation of aspirin and a reduced rate of hospitalization for primary stroke. The findings suggest that the provision of evidence‐based multifaceted large‐scale educational programs in primary care can be effective in changing prescriber behavior and positively impacting patient health outcomes.

show abstract

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

Abstract: Objective To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.

Cited by 5,941 publications

References 47 publications

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

In‐Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) Project

Using Large‐Scale Linkage Data to Evaluate the Effectiveness of a National Educational Program on Antithrombotic Prescribing and Associated Stroke Prevention in Primary Care

Contact Info

Product

Resources

About