Elevated Serum Levels of Alkaline Phosphatase and the Risk of Low Responsiveness to Clopidogrel.

Abstract

The elevated serum levels of alkaline phosphatase (ALP) serve as independent predictors of stent thrombosis after percutaneous coronary intervention (PCI). Our study aims at investigating the relationship between the serum ALP and the responsiveness to clopidogrel. Patients undergoing elective PCI were enrolled for the study, and all participants received a 300-mg clopidogrel loading dose. The responsiveness to clopidogrel was determined by thromboelastography (TEG), and low responsiveness to clopidogrel was defined based on two aspects: (1) adenosine diphosphate (ADP) -induced platelet-fibrin clot strength (MAADP) of > 47 mm and (2) ADP-induced platelet inhibition rate of < 50%. A logistic regression model analysis was used to calculate the risks of responsiveness to clopidogrel as odd ratios (OR) and 95% confidence intervals (CIs). Overall, 809 patients were considered for the study. They were divided into four quartile groups based on the serum ALP levels. A positive linear trend was observed in MAADP across the ALP quartiles (P for linear trend < 0.001), whereas ADP-induced platelet inhibition rate decreased across the ALP quartiles (P for linear trend = 0.007). When multiple confounders were adjusted, the highest ALP quartile correlated with an increased risk of low responsiveness to clopidogrel compared to the lowest ALP quartile (OR, 1.423; 95% CI, 1.017-1.991; P = 0.039). In the sensitivity analysis, the association remained significant for different definitions of low responsiveness to clopidogrel. The elevated serum levels of ALP are independently associated with an increased risk of low responsiveness to clopidogrel.