Objective: To compare the laboratory efficacy of P2Y12 receptor antagonists and to identify predictors of high on-treatment platelet reactivity (HTPR) in patients with an acute coronary syndrome treated with stent-PCI.
Methods: An analysis of PCI-VASP “all-comer” registry was performed. Efficacy of P2Y12 receptor antagonists was measured by phosphorylation of VASP 24±4 hours after a loading dose (LD) of clopidogrel (600mg), prasugrel (60mg) and ticagrelor (180mg), and expressed through a platelet reactivity index (PRI). High on-treatment platelet reactivity (HTPR) was defined as PRI ≥50%.
Results: Study group consisted of 589 patients who received clopidogrel (N=407, age 67±12.9 ys, 63.6% males), prasugrel (N=106, age 61.8±11.7 ys, 71.4% males) or ticagrelor (N=76, age 65.8±13.3 ys, 67.1% males). Patients selected for therapy with prasugrel were significantly younger than those who received clopidogrel (p=0.001).
Mean PRI was 44.2±23.1% after clopidogrel, 17.7±18.0% after prasugrel, and 18.8±17.0% after ticagrelor; p<0.001 for comparison of clopidogrel vs. prasugrel, and clopidogrel vs. ticagrelor, resp.). Proportion of patients with HTPR was 42.2% in clopidogrel group, 9.4% in prasugrel group, and 7.9% in ticagrelor group; p<0.001 for comparison of clopidogrel vs. prasugrel, and clopidogrel vs. ticagrelor, resp.).
From multiple variables* tested in prediction of HTPR, we found that HTPR was in ticagrelor treated patients significantly related to the platelet count (p=0.014), mean platelet volume (p=0.029) and multivessel disease (p=0.023). HTPR in patients treated with prasugrel was significatly related only to the mean platelet volume (p=0.02).
*variables included in the model: age, gender, BMI; history of: hypertension, diabetes, hyperlipidemia, MI, CABG, PAD, stroke, family history of CAD, cigarette smoking, CKD; therapy with: statin, ACEI, betablocker; single vs. multivessel disease, number of implanted stents; serum urea, creatinin, estimated GFR, hemoglobin, platelet count, mean platelet volume.
Conclusion: Residual platelet reactivity and proportion of patients with HTPR after LD of prasugrel/ticagrelor were significantly lower than after LD of clopidogrel. Factors known as predictors of higher platet reactivity did not influence efficacy of new generation of P2Y12 receptor antagonists. Family history of coronary artery disease platelet count and mean platelet volume were the single variables significantly related to HTPR in patients treated with prasugrel/ticagrelor.