Variability of non-response to aspirin in patients with peripheral arterial occlusive disease during long-term follow-up

Linnemann, Birgit; Prochnow, Stephanie; Mani, Helen; Schwonberg, Jan; Lindhoff-Last, Edelgard

doi:10.1007/s00277-009-0708-8

Cited by 18 publications

(31 citation statements)

References 33 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ingestion of aspirin increases the CV of the CEPI-cartridge in a dosedependent manner [34], and testing patients with ischemic heart disease instead of healthy volunteers results in higher CVs as well [35]. In two studies, a change in responsiveness to aspirin over time has been described which may at least partly be explained by the variation in CT values [36,37]. Based on these observations duplicate measurements and in case of inconsistent results repetitive platelet function testing should be performed to prevent misclassification.…”

Section: Discussionmentioning

confidence: 99%

Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

et al. 2010

Self Cite

View full text Add to dashboard Cite

Until now, the PFA-100® system has been considered unsuitable for monitoring clopidogrel efficacy. The authors evaluated platelet function in PAOD (peripheral arterial occlusive disease) patients using a new PFA-100® test cartridge (product name: INNOVANCE® PFA P2Y*) specifically designed for this purpose. Twenty-two stable PAOD patients on antithrombotic therapy with clopidogrel alone (n = 22) and 18 patients undergoing a peripheral catheter intervention, preliminarily treated with 100 mg/d aspirin followed by co-administration of clopidogrel (loading dose 300 mg, maintenance dose 75/d), were enrolled in this study. Defining non-responsiveness to clopidogrel as an aggregation response within the reference range (90% central interval), four (18.2%) non-responders using LTA induced by 5 µM ADP and six (27.3%) non-responders using LTA induced by 2 µM ADP (LateAggr >72.1% and >42.9%, respectively) were identified. INNOVANCE® PFA P2Y* determined six (27.3%) non-responders (CT<87s). Agreement between the two aggregometry assays and INNOVANCE® PFA P2Y* on the definition of clopidogrel response and non-response exceeded 70%. Only three patients were uniformly identified as clopidogrel non-responders by all three assays. When clopidogrel was co-administered with aspirin, two (11.1%) non-responders to clopidogrel were detected with INNOVANCE® PFA P2Y*, whereas ADP-induced LTA found all patients to be responsive. INNOVANCE® PFA P2Y* appears to be suitable for monitoring the effect of clopidogrel on platelet function. Its sensitivity in detecting responsiveness or non-responsiveness to clopidogrel is comparable to ADP-induced LTA. Additional prospective studies are needed to clarify the clinical relevance of the test results and classification obtained with INNOVANCE® PFA P2Y*. Response to Reviewers: FFM, 08/11/2009Dear editor and reviewers, Thank you for your comments on our manuscript. We performed the changes that you asked us to do. The changes are highlighted in blue. You will find a point-by-point response in the following. We hope that we addressed your concerns satisfactorily and that our manuscript is now acceptable for publication. Yours sincerelyDr. Birgit Linnemann, M.D. Ad reviewer 1:Ad 1: The reasons why we used lower ADP concentration in LTA was added. In a previous work we have shown that late aggregation using 2 μM ADP in non-adjusted PRP provides a good discrimination between clopidogrel treated patients and healthy subjects. However, we were also able to show that in platelet count-adjusted PRP, higher concentrations were necessary to differentiate between patients on clopidogrel treatment and subjects without clopidogrel medication. See reference 22.Ad 2: We agree that the figures 1-3 are quite similar. So we decided to remove fig. 1 and 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Abstra...

show abstract

Section: Discussionmentioning

confidence: 99%

Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…NSAIDs were not permitted (or had to be discontinued within a certain time period) in seven studies; 88,90,112,142,149,159,201 one study 155 stated that drugs known to affect PFTs were discontinued, and there were no details on NSAIDs in the remaining studies.…”

Section: Population and Test Characteristicsmentioning

confidence: 99%

“…Nineteen studies 88,90,93,95,112,113,121,125,142,147,149,155,159,162,164,169,174,187,201 were identified in this category, four of which were reported in abstract form only, 162,164,169,174 and one as a letter. 88 Populations had CAD (six studies In 12 studies 88,90,95,112,121,142,147,155,159,162,164,174 it appeared that patients were exclusively on monotherapy both at the time of the PFT and during follow-up.…”

Section: Population and Test Characteristicsmentioning

confidence: 99%

“…88 Populations had CAD (six studies In 12 studies 88,90,95,112,121,142,147,155,159,162,164,174 it appeared that patients were exclusively on monotherapy both at the time of the PFT and during follow-up. In two studies, 113,125 around 4% and 5% of patients were on dual therapy (aspirin + clopidogrel) at the time of the PFT.…”

Section: Population and Test Characteristicsmentioning

confidence: 99%

“…Of the 108 included studies with test data linked to clinical outcome data, 57 studies reported on a patient group solely or predominantly receiving aspirin as monotherapy at the time of testing, 46,76,86,88,90,92,93,95,99,105,[108][109][110]112,113,[115][116][117][118]121,123,125,127,128,132,133,135,137,138,142,[144][145][146][147][148][149][150][151][152][153][154][155]159,[162][163][164]166,168,169,171,174,186,187,189,193,195,196,…”

Section: Study Mappingmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

High On-Treatment Platelet Reactivity in Peripheral Endovascular Procedures

Spiliοpoulos¹,

Kassimis

Hatzidakis

et al. 2013

Cardiovasc Intervent Radiol

View full text Add to dashboard Cite

The use of aspirin is considered the "gold standard" for the decrease of major adverse cardiovascular events in patients with atherosclerosis, including peripheral arterial disease (PAD), whereas a dual-antiplatelet regimen with aspirin and clopidogrel is usually indicated for such patients after angioplasty and stent deployment. However, a substantial number of subsequent adverse events still occur, even in patients who receive double-antiplatelet therapy. The "high on-treatment platelet reactivity" (HTPR) phenomenon has been lately recognized and plays a major role in the management of patients with PAD. Greater and more rapid inhibition of platelet aggregation has become the goal for new antiplatelet agents with the expectation of further improving outcomes for percutaneous intervention for PAD. The purpose of this review article is to highlight current evidence regarding the prevalence, aetiology, and clinical implications of HTPR in PAD as well as to discuss the possibilities of novel alternative antiplatelet regiments.

show abstract

Variability of non-response to aspirin in patients with peripheral arterial occlusive disease during long-term follow-up

Cited by 18 publications

References 33 publications

Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

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

High On-Treatment Platelet Reactivity in Peripheral Endovascular Procedures

Contact Info

Product

Resources

About