Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial

Roberts, Jason D.; Wells, George; May, Michel R. Le; Labinaz, Marino; Glover, Chris; Froeschl, Michael; Dick, Alexander; Marquis, Jean-François; O’Brien, Edward R.; Gonçalves, Sandro Cadaval; Druce, Irena; Stewart, Alexandre F.R.; Gollob, Michael H.; So, Derek

doi:10.1016/s0140-6736(12)60161-5

Cited by 354 publications

(236 citation statements)

References 41 publications

Supporting

Mentioning

228

Contrasting

Unclassified

Order By: Relevance

“…Testy te można wykonywać w miejscu świadczenia opieki medycznej. Wciąż bez odpowiedzi pozostaje pytanie o znaczenie stosowania takich testów w zakresie selekcji pacjentów i o to, czy spersonalizowane leczenie oparte na genotypowaniu ma korzystny wpływ na kliniczne efekty i koszty leczenia [174]. European Medicines Agency (EMA) i amerykańska agencja Food and Drug Administration (FDA) sformułowały ostrzeżenia dotyczące osłabionego działania klopidogrelu w połączeniu z inhibitorami pompy protonowej, zwłaszcza z omeprazolem i esomeprazolem, które ograniczają metaboliczną aktywację klopidogrelu.…”

Section: Inne Klasy Lekówunclassified

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Roffi¹,

Patrono²,

Collet³

et al. 2015

Kardiol Pol

210

165

View full text Add to dashboard Cite

Section: Inne Klasy Lekówunclassified

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Roffi¹,

Patrono²,

Collet³

et al. 2015

Kardiol Pol

210

165

View full text Add to dashboard Cite

“…The best method of identifying high-risk individuals could be both genotyping and platelet-function testing (phenotype). The findings indicate that personalisation of antiplatelet therapy might decrease adverse ischaemic outcomes [27].…”

Section: Discussionmentioning

confidence: 93%

“…Moreover, this trial is also the first randomised investigation of selective use of prasugrel in CYP2C19*2 carriers after PCI, showing that this drug can reduce HTPR as opposed to clopidogrel. It can indicate that genetic factors do not influence the effectiveness of this new generation ADP-receptor antagonist [23].…”

Section: Genotyping -The Influence Of Gene Profile On Platelet Reactimentioning

confidence: 99%

Most Recent Evidence Behind Aggregometry and Genotyping Methods as Platelet Function Testing for Tailored Anti-Platelet Treatment Among PCI Patients

Gajda¹,

Kołtowski²,

Tomaniak³

2015

Adv Clin Exp Med

View full text Add to dashboard Cite

Aggregometry and genotyping are methods of platelet function testing, which can be beneficial for high-risk patients undergoing invasive cardiac procedures. An optimal level of platelet reactivity (PR) should be maintained. There are discrepancies between individuals and their response to clopidogrel, accounting for the incidence of poor responders from 5% to 44%. This phenomenon predisposes the patients to increased risk of ischaemic events and thereby overall poorer clinical outcome. Prasugrel and tricagrelor are newer without genetic correlation to their action, however associated with increased bleeding risk. Aggregometry methods assess platelet reactivity at the exact moment of blood sampling. They reflect "phenotype" of the patient and vary after drug administration or dose change. The most popular tests are Light Transmission Aggregometry, Vasodilator-Stimulated Protein, VerifyNow, Multiple Electrode Aggregometry and Thrombelastography. There is proven genetic correlation between some cytochrome enzymes on clopidogrel response. The most widely tested is gene CYP2C19, which produces the enzyme transforming clopidogrel into an active metabolite. The CYP2C19*2 allele carriers have higher PR which can result in more thrombotic events. The manuscript shows the most recent evidence behind platelet function testing. Aggregometry is shown to be beneficial in 5 trials and 1 meta-analysis, while one paper was of different opinion. Ten studies show a positive clinical effect of genotyping on patients' outcome, while one does not support it. The best method of identifying high-risk individuals could be both methods and personalisation of antiplatelet therapy may decrease adverse ischaemic outcomes (Adv Clin Exp Med 2015, 24, 4, 687-693).

show abstract

“…The GRAVITAS, ARCTIC, and TRILOGY-ACS trials have shown that bedside platelet reactivity testing did not result in clinical benefits, [54][55][56] but recently, a trial randomized patients undergoing percutaneous coronary intervention to either point-of-care genotyping and subsequent personalized treatment or standard clopidogrel treatment. 57 The point-of-care genotyping strategy showed significantly lower SyStematic Review on-treatment platelet reactivity in CYP2C19 loss-of-function carriers than the standard treatment strategy. However, the genetic substudy of the ARCTIC trial showed no benefits of genotyping.…”

Section: Evaluating Discordant Meta-analysesmentioning

confidence: 93%

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users

Osnabrugge

Head

Zijlstra

et al. 2015

Genetics in Medicine

View full text Add to dashboard Cite

Clopidogrel, in combination with aspirin, is a standard treatment for patients with acute coronary syndrome and is one of the top-selling drugs in the world.1,2 However, there is substantial interindividual variability in response. Polymorphisms of the cytochrome P450 (CYP) gene have been identified as a potential risk factor for nonresponse.3 This gene plays a central role in drug-metabolizing processes in the liver, and clopidogrel makes use of these processes to transform into an active metabolite capable of inhibiting platelet aggregation. Identification of CYP2C19 polymorphisms could lead to personalized treatment based on genotype in patients with acute coronary syndrome, and therefore, the US Food and Drug Administration recommends CYP2C19 genotyping for individualized antiplatelet management. 4 The association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel has been studied extensively, and several meta-analyses have summarized the results of those studies.5-8 Systematic reviews and meta-analyses are often considered the highest level of evidence, 9-11 and their popularity in the cardiovascular field increased almost 13 times as fast as the increase in number of published randomized clinical trials. 12However, the interpretation of meta-analyses is confusing when the conclusions of overlapping meta-analyses are discordant. Some meta-analyses on CYP2C19 loss-of-function and clinical efficacy of clopidogrel conclude that the association is proven, 7,8 whereas others conclude the opposite. 5,6 Our objective was to systematically evaluate the discordant evidence for the association between CYP2C19 loss-offunction alleles and clinical efficacy of clopidogrel through a critical methodological appraisal of published meta-analyses. MATERIALS AND METHODSOur review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, 13 and we consulted the Cochrane Handbook for Systematic Reviews of Interventions for methodological aspects of meta-analyses. We systematically investigated how 11 overlapping meta-analyses on the association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel could yield contradictory outcomes. The results of the meta-analyses differed because more recent metaanalyses included more primary studies and some had not included conference abstracts. Conclusions differed because between-study heterogeneity and publication bias were handled differently across meta-analyses. All meta-analyses on the clinical end point observed significant heterogeneity and several reported evidence for publication bias, but only one out of eight statistically significant meta-analyses concluded that therefore the association was unproven and one other refrained from quantifying a pooled estimate because of heterogeneity. For the end point stent thrombosis, all meta-analyses reported statistically significant associations with CYP2C19 loss-of-function alleles with no statistically significant evidence for heterogeneity, b...

show abstract

Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial

Cited by 354 publications

References 41 publications

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Most Recent Evidence Behind Aggregometry and Genotyping Methods as Platelet Function Testing for Tailored Anti-Platelet Treatment Among PCI Patients

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users

Contact Info

Product

Resources

About