What is an acceptable P2Y12 reaction unit (PRU) value for a patient with a history of coronary artery disease (CAD) who has received a drug-eluting stent and is taking antiplatelet therapy with medications like clopidogrel (Plavix), prasugrel (Effient), or ticagrelor (Brilinta)?

Acceptable PRU Values for CAD Patients with Drug-Eluting Stents on Antiplatelet Therapy

The optimal P2Y12 reaction unit (PRU) target range is <208-235 PRU to balance thrombotic and bleeding risk, though current guidelines do not recommend routine platelet function testing to adjust antiplatelet therapy in patients after stent placement. 1

Guideline Position on Platelet Function Testing

• Routine platelet function testing to adjust antiplatelet therapy before or after elective stenting is not recommended by the European Society of Cardiology 1
• Guidelines prioritize selecting the appropriate P2Y12 inhibitor based on clinical factors rather than adjusting therapy based on PRU values 1

Understanding PRU Thresholds (When Testing is Performed)

High On-Treatment Platelet Reactivity (HPR)

• HPR is defined as PRU >235 and is associated with increased risk of stent thrombosis and recurrent ischemic events 2, 3
• Approximately 56.5% of patients on standard-dose clopidogrel (75 mg) demonstrate HPR, compared to only 15% on low-dose prasugrel (5 mg) 2
• With potent P2Y12 inhibitors (prasugrel 10 mg or ticagrelor), HPR rates are markedly reduced to near 0% 3

Low On-Treatment Platelet Reactivity (LPR)

• LPR is generally defined as PRU <95-100 and is associated with increased bleeding risk 3
• Both prasugrel and ticagrelor produce very high rates of LPR, which explains their increased bleeding complications compared to clopidogrel 3

Target Range

• The therapeutic window appears to be PRU 95-235, balancing ischemic and bleeding risk 2, 3
• Prasugrel 10 mg typically achieves PRU values of 71.9±34.4, while prasugrel 5 mg achieves 174.6±60.2 2
• Clopidogrel 75 mg typically achieves PRU values of 223.4±72.9 2

Preferred P2Y12 Inhibitor Selection (The Guideline-Recommended Approach)

Rather than adjusting therapy based on PRU values, guidelines recommend selecting the most appropriate P2Y12 inhibitor upfront:

First-Line Therapy for ACS Patients

• Ticagrelor (180 mg loading, 90 mg twice daily) is recommended as first-line therapy for all ACS patients with drug-eluting stents 1, 4
• Ticagrelor achieves PRU values of approximately 48-52 at maintenance dosing 3

Alternative for PCI Patients

• Prasugrel (60 mg loading, 10 mg daily) is reasonable for P2Y12 inhibitor-naïve patients undergoing PCI, unless contraindicated by prior stroke/TIA, age ≥75 years, or weight <60 kg 1, 4

When to Use Clopidogrel

• Clopidogrel (600 mg loading, 75 mg daily) should be reserved for patients who cannot receive ticagrelor or prasugrel due to contraindications, prior intracranial bleeding, or need for oral anticoagulation 1, 4

Clinical Implications of Residual Platelet Reactivity

• Even with adequate P2Y12 inhibition (PRU <235), 45-54% of patients maintain normal platelet aggregation via protease-activated receptors (PAR-1 and PAR-4), which may explain recurrent ischemic events despite potent P2Y12 inhibition 5, 6
• This residual thrombin-mediated platelet activation is preserved in approximately 31-45% of patients on ticagrelor and 45-63% on prasugrel 6

Practical Approach When PRU Testing is Available

If platelet function testing is performed despite guideline recommendations against routine use:

• PRU >235: Consider switching from clopidogrel to ticagrelor (180 mg loading dose) or prasugrel (60 mg loading dose if no contraindications) 4, 2
• PRU 95-235: Continue current therapy; this represents the therapeutic target range 2, 3
• PRU <95: Consider bleeding risk assessment and potential dose reduction or switch to clopidogrel if recurrent bleeding occurs, though this is not guideline-supported 3

Duration of Therapy

• DAPT should be continued for 12 months in all ACS patients with drug-eluting stents unless excessive bleeding risk exists (e.g., PRECISE-DAPT score ≥25) 1, 4
• Daily aspirin dose should be 75-100 mg (81 mg in US) when combined with any P2Y12 inhibitor 1, 4

Common Pitfalls to Avoid

• Do not routinely order platelet function testing to guide therapy adjustments, as this is not supported by guidelines and may lead to unnecessary medication changes 1
• Do not use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated in ACS patients 4
• Do not forget to prescribe a proton pump inhibitor with DAPT to reduce gastrointestinal bleeding risk 1, 4
• Do not discontinue DAPT prematurely, especially within the first month after stent placement 4