Antiplatelet drug: Difference between revisions
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The ALPHEUS [[randomized controlled trial]] found no benefit of [[ticagrelor]] versus [[clopidogrel]] among stable coronary patients undergoing high-risk elective PCI (primary outcome in 35% vs 36% of patients)<ref name="pmid33202219">{{cite journal| author=Silvain J, Lattuca B, Beygui F, Rangé G, Motovska Z, Dillinger JG | display-authors=etal| title=Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial. | journal=Lancet | year= 2020 | volume= 396 | issue= 10264 | pages= 1737-1744 | pmid=33202219 | doi=10.1016/S0140-6736(20)32236-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33202219 }} </ref>. | The ALPHEUS [[randomized controlled trial]] found no benefit of [[ticagrelor]] versus [[clopidogrel]] among stable coronary patients undergoing high-risk elective PCI (primary outcome in 35% vs 36% of patients)<ref name="pmid33202219">{{cite journal| author=Silvain J, Lattuca B, Beygui F, Rangé G, Motovska Z, Dillinger JG | display-authors=etal| title=Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial. | journal=Lancet | year= 2020 | volume= 396 | issue= 10264 | pages= 1737-1744 | pmid=33202219 | doi=10.1016/S0140-6736(20)32236-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33202219 }} </ref>. | ||
The POPular AGE [[randomized controlled trial]] found no benefit of [[ticagrelor]] versus [[clopidogrel]] among patients aged 70 years or older with non-ST-elevation acute coronary syndrome (MACE in 11% vs 12% of patients)<ref name="pmid32334703">{{cite journal| author=Gimbel M, Qaderdan K, Willemsen L, Hermanides R, Bergmeijer T, de Vrey E | display-authors=etal| title=Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. | journal=Lancet | year= 2020 | volume= 395 | issue= 10233 | pages= 1374-1381 | pmid=32334703 | doi=10.1016/S0140-6736(20)30325-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334703 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=32926825 Review in: Ann Intern Med. 2020 Sep 15;173(6):JC28] </ref> | |||
The | The CHAMPION PCI [[randomized controlled trial]] found no benefit of [[cangrelor]] versus [[clopidogrel]] among patients "before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes" (MACE in 7.5% vs 7.1% of patients)<ref name="pmid19915221">{{cite journal| author=Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM | display-authors=etal| title=Platelet inhibition with cangrelor in patients undergoing PCI. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 24 | pages= 2318-29 | pmid=19915221 | doi=10.1056/NEJMoa0908628 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19915221 }} </ref>. | ||
The CHAMPION PLATFORM [[randomized controlled trial]] found no benefit of [[cangrelor]] ''added'' to [[clopidogrel]] among patients with acute coronary syndrome before percutaneous coronary intervention (PCI) (MACE in 7% vs 8% of patients) percutaneous coronary intervention (PCI). | |||
===Studies of patients with CYP2C19 loss-of-function | ===Studies of patients with CYP2C19 loss-of-function === | ||
The CHANCE-2 [[randomized controlled trial]] found benefit of [[ticagrelor]] versus [[clopidogrel]] (primary outcome: 6% vs 7.6%; hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008) among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles<ref name="pmid34708996">{{cite journal| author=Wang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC | display-authors=etal| title=Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA. | journal=N Engl J Med | year= 2021 | volume= 385 | issue= 27 | pages= 2520-2530 | pmid=34708996 | doi=10.1056/NEJMoa2111749 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34708996 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=35226525 Review in: Ann Intern Med. 2022 Mar;175(3):JC30] </ref>. | The CHANCE-2 [[randomized controlled trial]] found benefit of [[ticagrelor]] versus [[clopidogrel]] (primary outcome: 6% vs 7.6%; hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008) among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles<ref name="pmid34708996">{{cite journal| author=Wang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC | display-authors=etal| title=Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA. | journal=N Engl J Med | year= 2021 | volume= 385 | issue= 27 | pages= 2520-2530 | pmid=34708996 | doi=10.1056/NEJMoa2111749 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34708996 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=35226525 Review in: Ann Intern Med. 2022 Mar;175(3):JC30] </ref>. | ||
== Is there a best third-generation antiplatelet drug?== | == Is there a best third-generation antiplatelet drug?== | ||
Revision as of 18:34, 14 August 2022
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
An antiplatelet drug is a member of a class of pharmaceuticals that decreases platelet aggregation and inhibits thrombus formation. They are effective in the arterial circulation, where anticoagulants have little effect.
They are widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease.
The Most Important Antiplatelet Drugs
- COX-2 inhibitor / Cyclooxygenase inhibitors
- Phosphodiesterase inhibitors
- Cilostazol (Pletal)
- Glycoprotein IIB/IIIA inhibitors (intravenous use only)
- Abciximab (ReoPro)
- Eptifibatide (Integrilin)
- Tirofiban (Aggrastat)
- Defibrotide
- P2Y12 (Adenosine diphosphate receptors) inhibitors (thienopyridines)
- Clopidogrel (Plavix)
- Ticlopidine (Ticlid)
- P2Y12 (Adenosine diphosphate receptors) inhibitors (non-thienopyridines) - third generation
| Drug Group | Drug | Cost (UpToDate 08/2022) |
|---|---|---|
| Second generation P2Y12 (Adenosine diphosphate receptors) inhibitors (thienopyridines) |
Clopidogrel Ticlopidine |
$40 (generic) $112 |
| Third generation P2Y12 (Adenosine diphosphate receptors) inhibitors (non-thienopyridines) |
Prasugrel Ticagrelor |
$495 ($331 GoodRx) $511 |
Are third-generation agents better than second-generation agents?
Studies of all patients
The ALPHEUS randomized controlled trial found no benefit of ticagrelor versus clopidogrel among stable coronary patients undergoing high-risk elective PCI (primary outcome in 35% vs 36% of patients)[1].
The POPular AGE randomized controlled trial found no benefit of ticagrelor versus clopidogrel among patients aged 70 years or older with non-ST-elevation acute coronary syndrome (MACE in 11% vs 12% of patients)[2]
The CHAMPION PCI randomized controlled trial found no benefit of cangrelor versus clopidogrel among patients "before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes" (MACE in 7.5% vs 7.1% of patients)[3].
The CHAMPION PLATFORM randomized controlled trial found no benefit of cangrelor added to clopidogrel among patients with acute coronary syndrome before percutaneous coronary intervention (PCI) (MACE in 7% vs 8% of patients) percutaneous coronary intervention (PCI).
Studies of patients with CYP2C19 loss-of-function
The CHANCE-2 randomized controlled trial found benefit of ticagrelor versus clopidogrel (primary outcome: 6% vs 7.6%; hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008) among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles[4].
Is there a best third-generation antiplatelet drug?
The ISAR-REACT 5 randomized controlled trial found benefit of prasugrel versus ticagrelor (primary outcome: 6.9% vs 9.3%; hazard ratio, 1.36; 95% confidence interval, 1.09 to 1.70; P = 0.006) among patients with "acute coronary syndromes and for whom invasive evaluation was planned"[4].
The POPular Genetics randomized controlled trial found faster onset of action but no benefit of cangrelor versus ticagrelor among patients with "ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI"[5].
Should drug selection be driven by genetic testing and platelet function testing?
Guided therapy (drug choice based on genetic testing and platelet function testing may improve outcomes according to a systematic reveiw[6].
However, the key POPular Genetics randomized controlled trial found no benefit from a CYP2C19 guided therapy (primary outcome: 5.1 vs 5.9%;P = 0.44) among patients undergoing primary PCI with stent implantation[7].
See also
External links
References
- ↑ Silvain J, Lattuca B, Beygui F, Rangé G, Motovska Z, Dillinger JG; et al. (2020). "Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial". Lancet. 396 (10264): 1737–1744. doi:10.1016/S0140-6736(20)32236-4. PMID 33202219 Check
|pmid=value (help). - ↑ Gimbel M, Qaderdan K, Willemsen L, Hermanides R, Bergmeijer T, de Vrey E; et al. (2020). "Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial". Lancet. 395 (10233): 1374–1381. doi:10.1016/S0140-6736(20)30325-1. PMID 32334703 Check
|pmid=value (help). Review in: Ann Intern Med. 2020 Sep 15;173(6):JC28 - ↑ Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM; et al. (2009). "Platelet inhibition with cangrelor in patients undergoing PCI". N Engl J Med. 361 (24): 2318–29. doi:10.1056/NEJMoa0908628. PMID 19915221.
- ↑ 4.0 4.1 Wang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC; et al. (2021). "Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA". N Engl J Med. 385 (27): 2520–2530. doi:10.1056/NEJMoa2111749. PMID 34708996 Check
|pmid=value (help). Review in: Ann Intern Med. 2022 Mar;175(3):JC30 - ↑ Ubaid S, Ford TJ, Berry C, Murray HM, Wrigley B, Khan N; et al. (2019). "Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial". Thromb Haemost. 119 (7): 1171–1181. doi:10.1055/s-0039-1688789. PMID 31129911.
- ↑ Galli M, Benenati S, Capodanno D, Franchi F, Rollini F, D'Amario D; et al. (2021). "Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis". Lancet. 397 (10283): 1470–1483. doi:10.1016/S0140-6736(21)00533-X. PMID 33865495 Check
|pmid=value (help). - ↑ Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P; et al. (2019). "A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI". N Engl J Med. 381 (17): 1621–1631. doi:10.1056/NEJMoa1907096. PMID 31479209.