Does Clopidogrel Resistance Increase Over Time?: A Prospective Study in Acute Coronary Syndrome Patients

Objectives: Acute coronary syndromes (ACS) are life-threatening manifestations of cardiovascular disease caused by thrombus after endothelial injury. Clopidogrel, a P2Y12 inhibitor, is widely used in ACS, but its antiplatelet response may reduce by drug interactions, inadequate dosing, and CYP2C19 polymorphisms, causes clopidogrel resistance (CR). Mean platelet volume (MPV), an indicator of platelet size and activation, has also been associated with adverse cardiovascular outcomes. This study evaluated to show temporal changes in CR and MPV, the relationship between them in ACS patients.Materials and Methods: This single-center prospective study included 90 ACS patients aged 18–80 years treated with clopidogrel (600 mg loading dose followed by 75 mg/day). Blood samples for MPV and CR were obtained within 24 hours of admission and after one month defined as first and second analyses. Platelet aggregation analysed by Multiplate aggregometry. Cut off values were ≥460 AU(aggregation unit) for CR and ≥9.3 fL for MPV.Results: Most patients were male (83.3%), the mean age was 57.4±10.2 years and hypertension was the most common risk factor (49%). While MPV values didn’t differ between both analyses (8.58±0.75 vs 8.59±0.71 fL, p=0.89), CR significantly increased over time (254.76±180.9 vs 348.2±175.2 AU, p=0.0001). CR observed in 27 patients (32.35%) and MPV values were similar in these patients at both analyses. Among patients prescribed lipid-lowering therapy firstly, AU values increased significantly (251.08±170.34 AU vs 344.3 ±167.8 AU p=0.0001).Conclusions: Clopidogrel resistance increased over time without parallel changes in MPV, suggested different mechanisms underlying clopidogrel response. So routine CR test should be limited to selected high-risk patients.