Determinants of Reduced Antiplatelet Effect of Aspirin in Patients with Stable Coronary Artery Disease

Larsen, Susan Weng; Grove, Erik Lerkevang; Neergaard‐Petersen, Søs; Würtz, Morten; Hvas, Anne‐Mette; Kristensen, Steen Dalby

doi:10.1371/journal.pone.0126767

Cited by 39 publications

(35 citation statements)

References 45 publications

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“…Surprisingly, renal insufficiency was the only conventional risk factor independently predicting the primary and secondary end points in our study. We reported previously that prior myocardial infarction, type 2 diabetes mellitus, high body mass index, and high platelet count predicted increased platelet aggregation in stable CAD patients treated with aspirin monotherapy . In the present study, however, we found no effect of age, sex, type 2 diabetes mellitus, prior myocardial infarction, smoking, or body mass index on any end points.…”

Section: Discussioncontrasting

confidence: 90%

“…The study cohort represents a high‐risk population because all patients had documented CAD and either prior myocardial infarction, type 2 diabetes mellitus, or both. The study population and blood collection procedure were described previously in detail . Platelet‐aggregation data and their relation to prior myocardial infarction and stent thrombosis, type 2 diabetes mellitus, and renal insufficiency have been published previously .…”

Section: Methodsmentioning

confidence: 99%

“…The study population and blood collection procedure were described previously in detail. 9 Plateletaggregation data and their relation to prior myocardial infarction and stent thrombosis, type 2 diabetes mellitus, and renal insufficiency have been published previously. [10][11][12][13] Patients were recruited from November 2007 to January 2011 from the Western Denmark Heart Registry, which collects data on all interventional procedures performed in the western part of Denmark.…”

Section: Study Populationmentioning

confidence: 99%

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Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease

Larsen

Grove

Neergaard‐Petersen

et al. 2017

JAHA

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BackgroundIncreased platelet aggregation during antiplatelet therapy may predict cardiovascular events in patients with coronary artery disease. The majority of these patients receive aspirin monotherapy. We aimed to investigate whether high platelet‐aggregation levels predict cardiovascular events in stable coronary artery disease patients treated with aspirin.Methods and ResultsWe included 900 stable coronary artery disease patients with either previous myocardial infarction, type 2 diabetes mellitus, or both. All patients received single antithrombotic therapy with 75 mg aspirin daily. Platelet aggregation was evaluated 1 hour after aspirin intake using the VerifyNow Aspirin Assay (Accriva Diagnostics) and Multiplate Analyzer (Roche; agonists: arachidonic acid and collagen). Adherence to aspirin was confirmed by serum thromboxane B2. The primary end point was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At 3‐year follow‐up, 78 primary end points were registered. The primary end point did not occur more frequently in patients with high platelet‐aggregation levels (first versus fourth quartile) assessed by VerifyNow (hazard ratio: 0.5 [95% CI, 0.3–1.1], P=0.08) or Multiplate using arachidonic acid (hazard ratio: 1.0 [95% CI, 0.5–2.1], P=0.92) or collagen (hazard ratio: 1.4 [95% CI, 0.7–2.8], P=0.38). Similar results were found for the composite secondary end point (nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and all‐cause death) and the single end points. Thromboxane B2 levels did not predict any end points. Renal insufficiency was the only clinical risk factor predicting the primary and secondary end points.ConclusionsThis study is the largest to investigate platelet aggregation in stable coronary artery disease patients receiving aspirin as single antithrombotic therapy. We found that high platelet‐aggregation levels did not predict cardiovascular events.

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Section: Discussioncontrasting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

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Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease

Larsen

Grove

Neergaard‐Petersen

et al. 2017

JAHA

Self Cite

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“…Third, environment in vasculature seems to play important role, e.g. oxidative stress, inflammation, NO synthesis as well as patient characteristics which are causative of the former like as smoking, obesity and diabetes mellitus [9•, 123, 124•, 125•]. For example, brachial flow-mediated dilation was found to be inversely associated with platelet adhesion and aggregation [124•].…”

Section: Introductionmentioning

confidence: 99%

Effects of Aspirin on Endothelial Function and Hypertension

2016

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Purpose of reviewEndothelial dysfunction is intimately related to the development of various cardiovascular diseases, including hypertension, and is often used as a target for pharmacological treatment. The scope of this review is to assess effects of aspirin on endothelial function and their clinical implication in arterial hypertension.Recent findingsEmerging data indicate the role of platelets in the development of vascular inflammation due to the release of proinflammatory mediators, for example, triggered largely by thromboxane. Vascular inflammation further promotes oxidative stress, diminished synthesis of vasodilators, proaggregatory and procoagulant state. These changes translate into vasoconstriction, impaired circulation and thrombotic complications. Aspirin inhibits thromboxane synthesis, abolishes platelets activation and acetylates enzymes switching them to the synthesis of anti-inflammatory substances.SummaryAspirin pleiotropic effects have not been fully elucidated yet. In secondary prevention studies, the decrease in cardiovascular events with aspirin outweighs bleeding risks, but this is not the case in primary prevention settings. Ongoing trials will provide more evidence on whether to expand the use of aspirin or stay within current recommendations.

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“…Furthermore, many other factors influence individual response to treatment. High platelet count, diabetes mellitus type 2, high body mass index and prior myocardial infarction are confirmed as independent determinants of increased platelet aggregation [12]. The mentioned characteristics are supposed to be key factors in lowering response to antiplatelet treatment.…”

Section: Clinical Use Of Mea In Cardiologymentioning

confidence: 86%

Multiple electrode aggregometry – only for cardiologists?

Spałek

Żorniak

Krzemiński

2016

Ann. Acad. Med. Siles.

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Multiple electrode aggregometry is one of the newest technologies in platelet function monitoring. The idea of this assay is based on whole blood impedance aggregometry measurements. The main advantages of this device are rapid and easy use, no necessity of sample pre-processing or requiring a specialized laboratory. These features allow one to include this methodology in point-of-care testing methods that can be performed at the patient bedside. Five different pathways of platelet activation can be investigated by adding specific reaction agonists. Antiplatelet drugs, such as acetylsalicylic acid or clopidogrel, inhibit arachidonic acid-dependent and adenosine diphosphate-dependent pathways of platelet activation. Individual patient response to these drugs can be estimated using multiple electrode aggregometry. The identification of low-responders may result in reducing thrombosis events in this group and make antiplatelet treatment more effective. Furthermore, it is supposed to be a reliable method of estimating the risk of perioperative bleeding in adults undergoing cardiac surgery. Other potential clinical applications for this technology are being found. Many studies report its use in determining prognosis in severe sepsis, detecting heparin-induced thrombocytopenia and diagnosing von Willebrand disease. Although multiple electrode aggregometry seems to have great diagnostic potential, more tests need to be performed before it becomes standard hospital equipment. K E Y W O R DSmultiple electrode aggregometry, platelet function monitoring, antiplatelet therapy, platelet tests ST R ES ZCZ E NI EMetoda agregacji impedancyjnej jest jedną z najnowszych technik stosowanych w ocenie funkcji płytek krwi, wykorzystującą krew pełną jako środowisko reakcji. Zasada jej działania opiera się na pomiarach zmian impedancji, jakie następują na skutek agregacji płytek krwi po dodaniu egzogennego aktywatora. Najważniejszymi zaletami tej metody są: łatwość jej wykonania bez specjalistycznego laboratorium, brak konieczności wcześniejszego przetwarzania pobranej do badania próbki oraz szybkość w uzyskaniu wyników. Wszystkie te cechy pozwalają na wykonanie tego badania przy łóżku pacjenta. Metoda agregacji impedancyjnej pozwala na ocenę pięciu różnych szlaków aktywacji

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Determinants of Reduced Antiplatelet Effect of Aspirin in Patients with Stable Coronary Artery Disease

Cited by 39 publications

References 45 publications

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease

Effects of Aspirin on Endothelial Function and Hypertension

Multiple electrode aggregometry – only for cardiologists?

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