Low platelet disaggregation predicts poor response to 150 mg clopidogrel in patients with elevated platelet reactivity

Abstract

Raising the maintenance dose of clopidogrel to 150 mg enhances platelet inhibition (PI) in patients with elevated platelet reactivity (EPR); however, large differences were observed between individuals in the extent of this benefit. We aimed to find clinical and platelet function variables that might predict the response to 150 mg clopidogrel in patients with EPR. ADP 5 µM-stimulated peak aggregation (Agg_max), 6-minute late aggregation (Agg_late) and 6-minute disaggregation (disAgg) were measured with light transmission aggregometry (LTA) in a consecutive cohort of 202 patients admitted for emergent or elective percutaneous coronary intervention (PCI) after receiving a 600-mg loading dose of clopidogrel. PI was assessed 12 to 18 hours after loading dose and 30 days after the intervention. EPR was defined as a Agg_max value greater than 34%. From the first day of PCI, 85 patients with EPR received 150 mg clopidogrel for 30 days, while others with normal platelet reactivity (NPR) took 75 mg clopidogrel. Baseline clinical and LTA variables were analyzed in multivariable regression models. Administration of 150 mg clopidogrel enhanced PI and decreased the prevalence of EPR at 30 days compared to the peri-interventional period (Agg_max: 46.9 ± 8.3 vs. 37.3 ± 11.5; EPR: 100% vs. 62.4%; p < 0.001 in both cases); however, the achieved level of platelet reactivity was higher than patients with NPR (Agg_max: 20.6 ± 8.1 vs. 25.3 ± 10.8, p < 0.001). Multivariable logistic regression revealed low platelet disaggregation (odds ratio (OR): 12.49; 95% CI: 2.52–62.00; P = 0.002) and acute coronary syndrome (OR: 4.83; 95% CI: 1.54–15.09; P = 0.008) as independent predictors of EPR. The area under the receiver-operating-characteristic curve was 0.72 ± 0.06 for disaggregation to predict NPR after 150 mg clopidogrel. The optimal disaggregation cut-off was 16.5% with a sensitivity of 94% and a specificity of 43%. Administering 150 mg maintenance dose of clopidogrel enhanced antiplatelet potency; however, more than half of the patients persisted with EPR. Acute coronary syndrome and low (<16.5%) platelet disaggregation are independent predictors of poor benefit from dose shift.

• Platelet aggregation
• elevated platelet reactivity
• 150 mg clopidogrel
• predictors
• PCI