Body Mass Index and Plasma P-Selectin before Coronary Stenting Predict High Residual Platelet Reactivity at 6 Months on Dual Antiplatelet Therapy.

BACKGROUND: High residual platelet reactivity (HRPR) during dual antiplatelet therapy (DAPT) may impact clinical outcomes following percutaneous coronary interventions (PCI). However, whether any biomarkers assessed before PCI at DAPT loading may predict delayed maintenance HRPR is not clear. OBJECTIVE: The aim of this study was to determine whether conventional clinical or laboratory indices at loading before stenting may predict HRPR at 6 months of maintenance DAPT. METHODS: The study was designed on a single-center prospective cohort, and included 94 pre-PCI patients. All patients underwent elective PCI with drug-eluting stent implantation, and received DAPT with aspirin and clopidogrel. Platelet reactivity was assessed with 5 µmol/L of adenosine diphosphate-induced light transmission aggregometry before PCI, but after 24 h of DAPT loading, and repeated at 6 months. Baseline clinical characteristics, CYP2C19 polymorphism, C-reactive protein, soluble P-selectin, CD40L, interleukin-6, PAI-1 levels, and von Willebrand factor activity were analyzed. RESULTS: The incidence (light transmission aggregometry <50%) of prestent HRPR was 16%. By univariate regression, body mass index (BMI; p = 0.02), total cholesterol (p = 0.01), low-density lipoproteins (p = 0.004), CYP2C19*2 allele carriage (p = 0.006), soluble P-selectin (p = 0.009), and von Willebrand factor (p = 0.04) were linked to future HRPR. However, multivariate regression analysis suggested that only BMI and P-selectin were independent predictors of HRPR. CONCLUSIONS: Platelet reactivity before elective stenting is associated with numerous biomarkers; however, only BMI and soluble P-selectin were independent predictors of future HRPR during maintenance-phase DAPT. This may be important for future tailored antiplatelet strategies in patients with metabolic syndrome and diabetics.

Clopidogrel response variability: impact of genetic polymorphism and platelet biomarkers for predicting adverse outcomes poststenting.

The aim of this study was to triage platelet reactivity and adverse vascular outcomes after dual antiplatelet therapy due to percutaneous coronary intervention (PCI) dependent on CYP2C19*2 and CYP2C19*3 genotypes in patients with coronary artery disease. Fifty-five patients with coronary artery disease were studied serially pre-PCI and post-PCI. Platelet reactivity was assessed by conventional light transmission aggregometry, VerifyNow Analyzer, and thromboelastography with platelet mapping. Genetic testing was performed with allele-specific real-time polymerase chain reaction. Adverse events included vascular death, acute myocardial infarction, repeated PCI, definite stent thrombosis, and angina recurrence. The common genotype (GG) was found in 39 patients, heterozygous polymorphism CYP2C19 (GA) G681A allele was detected in 14 patients, and the rare homozygous polymorphism CYP2C19 (AA) G681A allele was exhibited in 2 patients. There were no CYP2C19*3 (Trp212Ter) carriers among index patients. The platelet reactivity was higher in patients with heterozygous and homozygous carriers compared with GG genotype. The largest differences were observed among GG, GA, and AA genotypes, which correlated with the average values of platelet aggregation (P = 0.02). There was a significant link between adverse events and high platelet reactivity assessed by light transmission aggregometry (P = 0.002). We found a trend between different genotype and VerifyNow readings (P = 0.057); moreover, their cumulative impact on adverse events was significant (P = 0.041). Platelet reactivity is higher in patients with heterozygous and homozygous carriers of CYP2C19*2 versus common genotype and may predict an increased risk of clopidogrel response variability and/or experiencing adverse cardiac events.

Independent Predictors of Major Adverse Events following Coronary Stenting over 28 Months of Follow-Up.

BACKGROUND: Despite recent advances in stent design and constantly improving protective pharmacological strategies, complications and adverse events following percutaneous coronary interventions (PCI) are still major factors influencing morbidity and mortality. Therefore, predicting secondary vascular occlusions represents an unmet medical need. OBJECTIVE: The aim of our study was to triage clinical and laboratory predictors of major adverse clinical events (MACE) following coronary stenting. METHODS: This was a prospective, case-controlled, single-center study, which included 94 consecutive patients with documented coronary disease who underwent PCI with drug-eluting stent (DES) implantation. All patients received dual antiplatelet therapy with aspirin and clopidogrel. Numerous clinical characteristics and laboratory biomarkers were assessed before stenting and were correlated with poststenting MACE over the mean follow-up of 28 months. MACE included death, nonfatal myocardial infarction, target vessel revascularisation, stroke, stent thrombosis, angina recurrence and instent restenosis. RESULTS: Twenty-three patients experienced MACE. Independent MACE predictors after PCI with DES implantation were antecedent diabetes mellitus (RR = 0.45; 95% CI 0.20-0.97; p = 0.045), prior thrombolytic therapy (RR = 0.42; 95% CI 0.27-0.83; p = 0.039), baseline plasminogen activator inhibitor -1 (PAI-1; p = 0.008) and plasma von Willebrand factor (vWF) activity (p = 0.007). Other clinical characteristics and laboratory indices showed no correlation with MACE. CONCLUSIONS: Background diabetes mellitus, prior thrombolytic therapy, PAI-1 and vWF prestenting activity may be useful for MACE prediction over 28 months of follow-up.