Comparisons Among Orally Effective P2Y12 Inhibitors
| Clopidogrel | Prasugrel | |||
|---|---|---|---|---|
| Pharmacology | Prodrug—requires conversion to active metabolite that irreversibly blocks P2Y12 receptor. | Prodrug—requires conversion to active metabolite that irreversibly blocks P2Y12 receptor. Conversion to active metabolite occurs more rapidly and to a greater degree than with clopidogrel. | ||
| Effect on platelet Aggregation | There is a delay of several hours before maximal antiplatelet effect is seen. | Onset of antiplatelet effect is faster and extent of inhibition of aggregation is greater than with clopidogrel. | ||
| Management strategy | Conservative | Invasive | Conservative | Invasive |
| Loading dose | 300 mg | 300–600 mg* | Generally not recommended for precatheterization use in UA/NSTEMI | 60 mg at time of PCI |
| Comment | * Optimal dose not established for invasive strategy although 600 mg generally preferred. | |||
| Timing | Initiate on presentation. | Give as soon as possible before or at the time of PCI. | Initiate as soon as coronary anatomy is known and decision is made to proceed with PCI | |
| Maintenance dose | 75 mg | 75 mg | 10 mg | |
| Comment | Optimal approach to dosing in individual patients based on genotype and individual antiplatelet effects not rigorously established. | Optimal individual dose not rigorously established (see comment to left). (150 mg for first 6 d is an alternative.) | Consider reduction to 5 mg in patients weighing <60 kg. The efficacy (or benefit) of prasugrel in those age ≥75 y is uncertain. Contraindicated in patients with a history of stroke or TIA. | |
| Duration | At least 1 mo and ideally up to 1 y | At least 1 y for BMS or DES | At least 1 y for DES | |
| Additional considerations | ||||
| Variability of Response | Greater compared with prasugrel. Factors impacting response in some patients may include genetic predisposition to convert parent compound to active metabolite and drug interactions (eg, PPIs). | Less compared with clopidogrel. Impact of genotype and concomitant medications appears less than with clopidogrel. | ||
| Platelet function Testing | Clinical utility not rigorously established. May be useful in selected patients with ischemic/thrombotic events while compliant with a clopidogrel regimen. | Clinical utility not rigorously established but less likely to be necessary given lesser degree of variation in response. | ||
| Genotyping | Identifies patients with a diminished (CYP2C19 * 2,* 3 alleles) or enhanced (CYP2C17 allele) ability to form active metabolite. Role of genotyping in clinical management not rigorously established. | Clinical utility not rigorously established but less likely to be necessary given lesser degree of variation in response. | ||
| Risk of bleeding | Standard dosing with clopidogrel is associated with less bleeding than with prasugrel. Higher doses of clopidogrel are associated with greater risk of bleeding than standard dose clopidogrel. | Risk of spontaneous, instrumented, and fatal bleeds higher with prasugrel compared with standard dose clopidogrel. | ||
| Transition to elective or nonurgent surgery | Wait at least 5 d after last dose. | Wait at least 7 d after last dose. | ||
BMS indicates bare-metal stent; DES, drug-eluting stent; PCI, percutaneous coronary intervention; PPI, proton pump inhibitor; TIA, transient ischemic attack; and UA/NSTEMI, unstable angina/non-ST–elevation myocardial infarction.