Antiplatelet drug

# 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
- Aspirin

## 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".

## 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).
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)
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".
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).
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.

## 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".

# Should drug selection be driven by genetic testing and platelet function testing?
According to the protocol for the ARTIC trial, the "VerifyNow P2Y12/aspirin assay measures platelet GPIIb/IIa-dependent aggregation to fibrinogen-coated beads in whole blood". Variations in function may be due to "insufficient active metabolite generation is the main explanation for clopidogrel antiplatelet response variability, and multiple factors may account for the reduced metabolism: (i) limited intestinal absorption; (ii) polymorphisms in genes encoding for the 2-step process oxidizing clopidogrel into its active metabolite; (iii) interactions with drugs such as lipophilic statins, calcium channel blockers, and proton pump inhibitors. Among these factors, carriage of the Cytochrome P450 CYP2C19*2 polymorphism has been associated with increased risk in stent thrombosis and myocardial infarction especially in patients with ACS who have undergone stent PCI. 6 In addition to the above mechanisms, increased body weight and diabetes have been associated with increased baseline platelet reactivity and a diminished antiplatelet response to clopidogrel".
Guided therapy (drug choice based on genetic testing and platelet function testing may improve outcomes according to a systematic reveiw.

### 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 , 0.98 to 1.29; P=0.10) among "patients scheduled for coronary stenting"
- 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 078-129; p=098) among "patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome"
- Almost all patients in the control group 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 reduced (primary outcome: 5.1 vs 5.9%;P = 0.44) among patients undergoing primary PCI with stent implantation.
- 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".