What test is used to identify clopidogrel (Plavix) resistance?

Clopidogrel Resistance Testing

Light transmission aggregometry (LTA) using ADP as the agonist is the reference standard test for identifying clopidogrel resistance, though VASP phosphorylation assay and VerifyNow P2Y12 are also validated alternatives. 1

Primary Testing Methods

Gold Standard

• LTA with ADP remains the reference standard according to European Society of Cardiology guidelines for assessing clopidogrel's antiplatelet effect 1
• This test measures platelet aggregation in response to ADP stimulation after clopidogrel administration 2

Alternative Validated Tests

• VASP phosphorylation assay directly measures clopidogrel's effect on the platelet P2Y12 receptor (the drug's actual pharmacological target), making it mechanistically superior 1
• VerifyNow P2Y12 is the most practical point-of-care test available, providing rapid results at bedside 2, 3
• Multiplate analyzer and other point-of-care devices are available but less well-validated 4

Defining Resistance: Critical Cut-off Values

LTA Cut-offs

• Greater than 60% aggregation with 20 mM ADP 1
• Greater than 50% aggregation with 5 mM ADP 1
• Greater than 70% aggregation with 10 mM ADP (specifically associated with stent thrombosis risk) 1

VASP Cut-off

• Platelet reactivity index (PRI) greater than 50% indicates inadequate clopidogrel response 1

VerifyNow Cut-off

• Device-specific values established through ROC analysis in post-PCI patients, typically around 235 PRU (P2Y12 reaction units) 5

Critical Limitations You Must Understand

Poor Agreement Between Tests

• The correlation between different testing methods is only modest (66-78% agreement), and a patient may be classified as resistant by one method but responsive by another 1, 4
• In one study, only 47% of patients were consistently classified as "good" or "poor responders" by all three major tests (LTA, VerifyNow, VASP) 5
• 33% of patients were defined as "poor responders" by only one test, highlighting the lack of standardization 5

Clinical Utility Controversy

• Cut-off values are not standardized and vary widely between studies 1
• Recent randomized trials testing individualized therapy based on single test results have shown negative outcomes, likely due to poor inter-test agreement 5
• Test results can be affected by blood preservative choice and pre-analytical errors 1

Prevalence and Clinical Context

• Clopidogrel resistance frequency ranges from 5-44% depending on the test used 1
• Approximately 21% of patients undergoing PCI show incomplete platelet inhibition 1
• Resistance rates are dose-dependent: lower prevalence with 600 mg loading doses versus 300 mg, and with 150 mg/day maintenance versus 75 mg/day 1

Genetic Testing Alternative

• The FDA label specifically mentions that tests are available to identify CYP2C19 poor metabolizers, who form less active metabolite and have reduced clopidogrel effectiveness 6
• Genetic testing for CYP2C19 polymorphisms provides a different approach to identifying patients at risk for treatment failure 6
• Consider alternative P2Y12 inhibitors in patients identified as CYP2C19 poor metabolizers 6

Practical Recommendation

If you need to test for clopidogrel resistance in clinical practice, use LTA with ADP if available for the most validated results, or VerifyNow P2Y12 for point-of-care convenience 1, 2. However, recognize that no single test perfectly predicts clinical outcomes, and the modest correlation between tests (66-78%) means you may need to interpret borderline results cautiously 1, 4. Consider genetic testing for CYP2C19 as a complementary approach 6.