A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease
Abstract Background Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y12-antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y12-antagonists are clopidogrel, prasugrel and ticagre...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Thrombosis Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12959-019-0197-5 |
| _version_ | 1819057294187429888 |
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| author | Ellen M. K. Warlo Harald Arnesen Ingebjørg Seljeflot |
| author_facet | Ellen M. K. Warlo Harald Arnesen Ingebjørg Seljeflot |
| author_sort | Ellen M. K. Warlo |
| collection | DOAJ |
| description | Abstract Background Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y12-antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y12-antagonists are clopidogrel, prasugrel and ticagrelor. Despite DAPT, some patients experience adverse cardiovascular events, and insufficient platelet inhibition has been suggested as a possible cause. In the present review we have performed a literature search on prevalence, mechanisms and clinical implications of resistance to P2Y12 inhibitors. Methods The PubMed database was searched for relevant papers and 11 meta-analyses were included. P2Y12 resistance is measured by stimulating platelets with ADP ex vivo and the most used assays are vasodilator stimulated phosphoprotein (VASP), Multiplate, VerifyNow (VN) and light transmission aggregometry (LTA). Discussion/conclusion The frequency of high platelet reactivity (HPR) during clopidogrel therapy is predicted to be 30%. Genetic polymorphisms and drug-drug interactions are discussed to explain a significant part of this inter-individual variation. HPR during prasugrel and ticagrelor treatment is estimated to be 3–15% and 0–3%, respectively. This lower frequency is explained by less complicated and more efficient generation of the active metabolite compared to clopidogrel. Meta-analyses do show a positive effect of adjusting standard clopidogrel treatment based on platelet function testing. Despite this, personalized therapy is not recommended because no large-scale RCT have shown any clinical benefit. For patients on prasugrel and ticagrelor, platelet function testing is not recommended due to low occurrence of HPR. |
| first_indexed | 2024-12-21T13:37:01Z |
| format | Article |
| id | doaj.art-2002f25aa91f4441b077e1fbdb64fa43 |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-12-21T13:37:01Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-2002f25aa91f4441b077e1fbdb64fa432022-12-21T19:02:08ZengBMCThrombosis Journal1477-95602019-05-011711910.1186/s12959-019-0197-5A brief review on resistance to P2Y12 receptor antagonism in coronary artery diseaseEllen M. K. Warlo0Harald Arnesen1Ingebjørg Seljeflot2Center for Clinical Heart Research, Department of Cardiology, Oslo University HospitalCenter for Clinical Heart Research, Department of Cardiology, Oslo University HospitalCenter for Clinical Heart Research, Department of Cardiology, Oslo University HospitalAbstract Background Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y12-antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y12-antagonists are clopidogrel, prasugrel and ticagrelor. Despite DAPT, some patients experience adverse cardiovascular events, and insufficient platelet inhibition has been suggested as a possible cause. In the present review we have performed a literature search on prevalence, mechanisms and clinical implications of resistance to P2Y12 inhibitors. Methods The PubMed database was searched for relevant papers and 11 meta-analyses were included. P2Y12 resistance is measured by stimulating platelets with ADP ex vivo and the most used assays are vasodilator stimulated phosphoprotein (VASP), Multiplate, VerifyNow (VN) and light transmission aggregometry (LTA). Discussion/conclusion The frequency of high platelet reactivity (HPR) during clopidogrel therapy is predicted to be 30%. Genetic polymorphisms and drug-drug interactions are discussed to explain a significant part of this inter-individual variation. HPR during prasugrel and ticagrelor treatment is estimated to be 3–15% and 0–3%, respectively. This lower frequency is explained by less complicated and more efficient generation of the active metabolite compared to clopidogrel. Meta-analyses do show a positive effect of adjusting standard clopidogrel treatment based on platelet function testing. Despite this, personalized therapy is not recommended because no large-scale RCT have shown any clinical benefit. For patients on prasugrel and ticagrelor, platelet function testing is not recommended due to low occurrence of HPR.http://link.springer.com/article/10.1186/s12959-019-0197-5P2Y12 receptor antagonistsResidual platelet reactivityClopidogrelPrasugrelTicagrelor |
| spellingShingle | Ellen M. K. Warlo Harald Arnesen Ingebjørg Seljeflot A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease Thrombosis Journal P2Y12 receptor antagonists Residual platelet reactivity Clopidogrel Prasugrel Ticagrelor |
| title | A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease |
| title_full | A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease |
| title_fullStr | A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease |
| title_full_unstemmed | A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease |
| title_short | A brief review on resistance to P2Y12 receptor antagonism in coronary artery disease |
| title_sort | brief review on resistance to p2y12 receptor antagonism in coronary artery disease |
| topic | P2Y12 receptor antagonists Residual platelet reactivity Clopidogrel Prasugrel Ticagrelor |
| url | http://link.springer.com/article/10.1186/s12959-019-0197-5 |
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