Non-compliance is the predominant cause of aspirin resistance in chronic coronary arterial disease patients

Schwartz, Kenneth A.; Schwartz, Dianne E.; Barber, Kimberly; Reeves, Mathew; Franco, Anthony C. De

doi:10.1186/1479-5876-6-46

Cited by 59 publications

(46 citation statements)

References 38 publications

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“…46,48 Thus, in fully compliant patients, aspirin resistance may be a rare but important biological phenomenon. 45,49,50 Another important variable to control for in studies of aspirin resistance is the presence of interacting drugs. A well-described interaction between aspirin and NSAIDs such as ibuprofen and naproxen [but not rofecoxib (Vioxx ® , Merck Sharpe & Dohme), celecoxib (Celebrex ® , Pfizer), meloxicam, acetaminophen or diclofenac] has been shown to have an impact on platelet aggregation responses.…”

Section: Platelet Function Assaysmentioning

confidence: 99%

The prognostic utility of tests of platelet function for the detection of ‘aspirin resistance’ in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation

Dretzke

Riley

Lordkipanidzé

et al. 2015

Health Technology Assessment

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BackgroundThe use of aspirin is well established for secondary prevention of cardiovascular disease. However, a proportion of patients suffer repeat cardiovascular events despite being prescribed aspirin treatment. It is uncertain whether or not this is due to an inherent inability of aspirin to sufficiently modify platelet activity. This report aims to investigate whether or not insufficient platelet function inhibition by aspirin (‘aspirin resistance‘), as defined using platelet function tests (PFTs), is linked to the occurrence of adverse clinical outcomes, and further, whether or not patients at risk of future adverse clinical events can be identified through PFTs.ObjectivesTo review systematically the clinical effectiveness and cost-effectiveness evidence regarding the association between PFT designation of ‘aspirin resistance’ and the risk of adverse clinical outcome(s) in patients prescribed aspirin therapy. To undertake exploratory model-based cost-effectiveness analysis on the use of PFTs.Data sourcesBibliographic databases (e.g. MEDLINE from inception and EMBASE from 1980), conference proceedings and ongoing trial registries up to April 2012.MethodsStandard systematic review methods were used for identifying clinical and cost studies. A risk-of-bias assessment tool was adapted from checklists for prognostic and diagnostic studies. (Un)adjusted odds and hazard ratios for the association between ‘aspirin resistance’, for different PFTs, and clinical outcomes are presented; however, heterogeneity between studies precluded pooling of results. A speculative economic model of a PFT and change of therapy strategy was developed.ResultsOne hundred and eight relevant studies using a variety of PFTs, 58 in patients on aspirin monotherapy, were analysed in detail. Results indicated that some PFTs may have some prognostic utility, i.e. a trend for more clinical events to be associated with groups classified as ‘aspirin resistant’. Methodological and clinical heterogeneity prevented a quantitative summary of prognostic effect. Study-level effect sizes were generally small and absolute outcome risk was not substantially different between ‘aspirin resistant’ and ‘aspirin sensitive’ designations.No studies on the cost-effectiveness of PFTs for ‘aspirin resistance’ were identified. Based on assumptions of PFTs being able to accurately identify patients at high risk of clinical events and such patients benefiting from treatment modification, the economic model found that a test–treat strategy was likely to be cost-effective. However, neither assumption is currently evidence based.LimitationsPoor or incomplete reporting of studies suggests a potentially large volume of inaccessible data. Analyses were confined to studies on patients prescribed aspirin as sole antiplatelet therapy at the time of PFT. Clinical and methodological heterogeneity across studies precluded meta-analysis. Given the lack of robust data the economic modelling was speculative.ConclusionsAlthough evidence indicates that some PFTs may have some prognostic value, methodological and clinical heterogeneity between studies and different approaches to analyses create confusion and inconsistency in prognostic results, and prevented a quantitative summary of their prognostic effect. Protocol-driven and adequately powered primary studies are needed, using standardised methods of measurements to evaluate the prognostic ability of each test in the same population(s), and ideally presenting individual patient data. For any PFT to inform individual risk prediction, it will likely need to be considered in combination with other prognostic factors, within a prognostic model.Study registrationThis study is registered as PROSPERO 2012:CRD42012002151.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Platelet Function Assaysmentioning

confidence: 99%

The prognostic utility of tests of platelet function for the detection of ‘aspirin resistance’ in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation

Dretzke

Riley

Lordkipanidzé

et al. 2015

Health Technology Assessment

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“…Noncompliance is probably the major cause of antiplatelet therapy "resistance" [27,28]. Cigarette smoking, depression, diabetes mellitus, low education level and female sex were identified as predictors of noncompliance and treatment discontinuation [29].…”

Section: Reduced Bioavailability Of Anti-platelet Drugsmentioning

confidence: 99%

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Mărginean

Bănescu

Scridon

et al. 2016

The Journal of Critical Care Medicine

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It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low-or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

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“…Noncompliance is the most important cause of an inadequate aspirin response to prescribed aspirin. 8,15 Platelets from 17 of 192 patients with chronic coronary artery disease responded to AA stimulation in a light aggregometer, demonstrating that the platelets were not inhibited by the prescribed aspirin ( Figure 2). These patients had been prescribed aspirin for at least 1 month.…”

Section: Incidence and Significancementioning

confidence: 99%

“…Among participants whose compliance was assured because they were observed to ingest aspirin, only 3% could be conservatively classified as aspirin resistant. 15 Another study of 136 patients evaluated after coronary stenting with AA-stimulated light aggregometry identified 19 patients with an inadequate aspirin response. 16 After observed aspirin ingestion 18 of the 19 responded to aspirin, showing that the initial nonresponse was also because of noncompliance.…”

Section: Incidence and Significancementioning

confidence: 99%

Aspirin Resistance

Schwartz

2011

The Neurohospitalist

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Aspirin is an inexpensive, readily available medication that reduces the risk of subsequent vascular disease by about 25% in patients with known occlusive vascular disease. Aspirin's beneficial effect is mediated via inhibition of arachidonic acid (AA) activation of platelets and is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Patients who are assumed to be taking their aspirin, but who do not demonstrate an aspirin effect are labeled as, ''aspirin resistant.'' This is an unfortunate designation as the vast majority of patients labeled as ''aspirin resistant'' are noncompliant. Noncompliance is demonstrated in multiple studies that use repeat testing for platelet inhibition in patients with an initial inadequate response to aspirin. When the test is repeated under condition where ingestion of the test aspirin is assured, the patients' platelets are inhibited. Instead of using the term ''aspirin resistance,'' this review will use ''inadequate response to aspirin.'' Patients with an inadequate aspirin response have an increased likelihood for subsequent vascular events. Detection and treatment of an inadequate aspirin response would be facilitated by the development of a bedside assay that uses whole blood, is technically simple, inexpensive, sensitive, specific, reproducible, and provides an answer in a few minutes. Future research in patients with an inadequate response to aspirin should focus on mechanisms to improve compliance, which should decrease their risk of future vascular events.

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Non-compliance is the predominant cause of aspirin resistance in chronic coronary arterial disease patients

Cited by 59 publications

References 38 publications

The prognostic utility of tests of platelet function for the detection of ‘aspirin resistance’ in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation

The prognostic utility of tests of platelet function for the detection of ‘aspirin resistance’ in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Aspirin Resistance

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