Association of cyclooxygenase-1-dependent and -independent platelet function assays with adverse clinical outcomes in...

Area of Science:

• Cardiology
• Pharmacology
• Clinical Medicine

Background:

• Poor clinical outcomes in aspirin-treated patients are often attributed to aspirin resistance.
• Aspirin resistance may stem from insufficient inhibition of platelet cyclooxygenase-1 (COX-1) by aspirin.

Purpose of the Study:

• To prospectively evaluate the correlation between COX-1-dependent and other platelet function assays and clinical outcomes in aspirin-treated patients.
• To investigate the mechanisms underlying poor clinical outcomes in patients undergoing percutaneous coronary intervention.

Main Methods:

• Prospective study of 700 aspirin-treated patients undergoing percutaneous coronary intervention.
• Platelet function assessed using serum thromboxane B(2), arachidonic acid-stimulated markers, and Platelet Function Analyzer (PFA)-100 (collagen-epinephrine and collagen-ADP closure time).
• Adverse clinical outcomes (death, cardiovascular death, major adverse cardiovascular events) assessed over approximately 25 months.

Main Results:

• Univariate analysis showed no association between COX-1-dependent assays (serum thromboxane B(2)) and adverse outcomes.
• The COX-1-independent PFA-100 collagen-ADP closure time <65 seconds was associated with major adverse cardiovascular events (P=0.0149).
• After adjustment for covariates, both serum thromboxane B(2) >3.1 ng/mL and PFA-100 collagen-ADP CT <65 seconds correlated with major adverse cardiovascular events. Indirect COX-1 measures were not significantly associated.

Conclusions:

• Residual platelet COX-1 function (serum thromboxane B(2)) and COX-1-independent platelet function (PFA-100 collagen-ADP CT) correlate with major adverse cardiovascular events in aspirin-treated patients.
• Indirect COX-1-dependent assays did not significantly correlate with adverse outcomes.
• The findings suggest multiple mechanisms, beyond inadequate COX-1 inhibition, contribute to poor clinical outcomes, rendering the term 'aspirin resistance' potentially inappropriate.