Antiplatelet drug: Difference between revisions
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====Platelet function testing==== | ====Platelet function testing==== | ||
The ARTIC [[randomized controlled trial]] found no benefit from guided therapy with platelet function testing (primary outcomes: 34.6% vs 31.1% ; hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10) among "patients scheduled for coronary stenting"<ref name="pmid23121439">{{cite journal| author=Collet JP, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C | display-authors=etal| title=Bedside monitoring to adjust antiplatelet therapy for coronary stenting. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 22 | pages= 2100-9 | pmid=23121439 | doi=10.1056/NEJMoa1209979 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23121439 }} </ref> | |||
* Almost all patients received [[clopidogrel]] in the usual care group | |||
* ''Only 55% of patients had long-term changes in their therapy based on testing'' | |||
The ANTARCTIC [[randomized controlled trial]] found no benefit from guided therapy with platelet function testing (primary outcomes: 28% vs 28%; hazard ratio 1.003, 95% CI 0·78-1·29; p=0·98) among "patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome"<ref name="pmid27581531">{{cite journal| author=Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C | display-authors=etal| title=Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. | journal=Lancet | year= 2016 | volume= 388 | issue= 10055 | pages= 2015-2022 | pmid=27581531 | doi=10.1016/S0140-6736(16)31323-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27581531 }} </ref> | |||
* All patients received [[prasugrel]] which as less abnormal alleles of [cytochrome P450]] CYP2C19. | |||
====Cytochrome P450 CYP2C19 testing==== | ====Cytochrome P450 CYP2C19 testing==== | ||
The | The POPular Genetics [[randomized controlled trial]] found benefit from a [[cytochrome P450]] CYP2C19 guided therapy due to lower (minor) bleeding although the MACE was not reduce (primary outcome: 5.1 vs 5.9%;P = 0.44) among patients undergoing primary PCI with stent implantation<ref name="pmid31479209">{{cite journal| author=Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P | display-authors=etal| title=A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. | journal=N Engl J Med | year= 2019 | volume= 381 | issue= 17 | pages= 1621-1631 | pmid=31479209 | doi=10.1056/NEJMoa1907096 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31479209 }} </ref>. | ||
* This trial tested for [[cytochrome P450]] CYP2C19*2 and CYP2C19*2 alleles. | * This trial tested for [[cytochrome P450]] CYP2C19*2 and CYP2C19*2 alleles. | ||
* The accompanying editorial concluded "the POPular Genetics trial provides strong support for a genotype-guided approach to clopidogrel prescribing in patients of European ancestry"<ref name="pmid31644850">{{cite journal| author=Roden DM| title=Clopidogrel Pharmacogenetics - Why the Wait? | journal=N Engl J Med | year= 2019 | volume= 381 | issue= 17 | pages= 1677-1678 | pmid=31644850 | doi=10.1056/NEJMe1911496 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31644850 }} </ref>. | * The accompanying editorial concluded "the POPular Genetics trial provides strong support for a genotype-guided approach to clopidogrel prescribing in patients of European ancestry"<ref name="pmid31644850">{{cite journal| author=Roden DM| title=Clopidogrel Pharmacogenetics - Why the Wait? | journal=N Engl J Med | year= 2019 | volume= 381 | issue= 17 | pages= 1677-1678 | pmid=31644850 | doi=10.1056/NEJMe1911496 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31644850 }} </ref>. | ||
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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
| Drug Group | Drug | Time to onset/peak action | Cost (UpToDate 08/2022) |
|---|---|---|---|
| Thienopyridines | Ticlopidine(first generation) Clopidogrel (second generation) Prasugrel (third generation) |
50 to 100 mg: 2 days; 5-7 days <30 minutes; 4 hours |
$112 $195 $495 ($331 GoodRx) |
| Non-thienopyridines | Ticagrelor | <30 minutes; 2 hours | $511 |
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
These are prodrugs that require in vivo biotransformation to active metabolite by the cytochrome P450 isoenzymes. With the exception of prasugrel, these drugs are effected by common CYP polymorphisms and less commonly by P2Y12 variants.
- First generation: Ticlopidine (Ticlid)
- Second gereration:Clopidogrel (Plavix)
- Third gereration: Prasugrel
Non-thienopyridines
These drugs bind directly to P2Y12.
- Cangrelor (intravenous)
- Ticagrelor (oral)
Comparative studies
Are newer thienopyridine (third-generation) agents better than older thienopyridine (second-generation) agents?
Studies of all patients
The TRILOGY ACS randomized controlled trial found no benefit of prasugrel versus clopidogrel (primary outcome: 13.9% vs 16%; hazard ratio 0.91; 0.79 to 1.05; P=0.21) among "patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization"[1].
Are non-thienopyridines agents better than thienopyridine (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)[2].
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)[3]
The ISAR-REACT 5 randomized controlled trial found harm of ticagrelor versus prasugrel (primary outcome: 9.3% vs 6.9%; 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 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)[5].
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 non-thienopyridine antiplatelet drug?
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"[6].
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[7].
Platelet function testing
The ARTIC randomized controlled trial found no benefit from guided therapy with platelet function testing (primary outcomes: 34.6% vs 31.1% ; hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10) among "patients scheduled for coronary stenting"[8]
- Almost all patients received clopidogrel in the usual care group
- Only 55% of patients had long-term changes in their therapy based on testing
The ANTARCTIC randomized controlled trial found no benefit from guided therapy with platelet function testing (primary outcomes: 28% vs 28%; hazard ratio 1.003, 95% CI 0·78-1·29; p=0·98) among "patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome"[9]
- All patients received prasugrel which as less abnormal alleles of [cytochrome P450]] CYP2C19.
Cytochrome P450 CYP2C19 testing
The POPular Genetics randomized controlled trial found benefit from a cytochrome P450 CYP2C19 guided therapy due to lower (minor) bleeding although the MACE was not reduce (primary outcome: 5.1 vs 5.9%;P = 0.44) among patients undergoing primary PCI with stent implantation[10].
- This trial tested for cytochrome P450 CYP2C19*2 and CYP2C19*2 alleles.
- The accompanying editorial concluded "the POPular Genetics trial provides strong support for a genotype-guided approach to clopidogrel prescribing in patients of European ancestry"[11].
See also
External links
References
- ↑ Roe MT, Armstrong PW, Fox KA, White HD, Prabhakaran D, Goodman SG; et al. (2012). "Prasugrel versus clopidogrel for acute coronary syndromes without revascularization". N Engl J Med. 367 (14): 1297–309. doi:10.1056/NEJMoa1205512. PMID 22920930.
- ↑ 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 - ↑ 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 - ↑ 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.
- ↑ 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). - ↑ Collet JP, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C; et al. (2012). "Bedside monitoring to adjust antiplatelet therapy for coronary stenting". N Engl J Med. 367 (22): 2100–9. doi:10.1056/NEJMoa1209979. PMID 23121439.
- ↑ Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C; et al. (2016). "Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial". Lancet. 388 (10055): 2015–2022. doi:10.1016/S0140-6736(16)31323-X. PMID 27581531.
- ↑ 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.
- ↑ Roden DM (2019). "Clopidogrel Pharmacogenetics - Why the Wait?". N Engl J Med. 381 (17): 1677–1678. doi:10.1056/NEJMe1911496. PMID 31644850.