Evaluation of Clinical Risk Factors to Predict High On-Treatment Platelet Reactivity and Outcome in Patients with Stable Coronary Artery Disease (PREDICT-STABLE)

Objectives This study was designed to identify the multivariate effect of clinical risk factors on high on-treatment platelet reactivity (HPR) and 12 months major adverse events (MACE) under treatment with aspirin and clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI). Methods 739 consecutive patients with stable coronary artery disease (CAD) undergoing PCI were recruited. On-treatment platelet aggregation was tested by light transmittance aggregometry. Clinical risk factors and MACE during one-year follow-up were recorded. An independent population of 591 patients served as validation cohort. Results Degree of on-treatment platelet aggregation was influenced by different clinical risk factors. In multivariate regression analysis older age, diabetes mellitus, elevated BMI, renal function and left ventricular ejection fraction were independent predictors of HPR. After weighing these variables according to their estimates in multivariate regression model, we developed a score to predict HPR in stable CAD patients undergoing elective PCI (PREDICT-STABLE Score, ranging 0-9). Patients with a high score were significantly more likely to develop MACE within one year of follow-up, 3.4% (score 0-3), 6.3% (score 4-6) and 10.3% (score 7-9); odds ratio 3.23, P=0.02 for score 7-9 vs. 0-3. This association was confirmed in the validation cohort. Conclusions Variability of on-treatment platelet function and associated outcome is mainly influenced by clinical risk variables. Identification of high risk patients (e.g. with high PREDICT-STABLE score) might help to identify risk groups that benefit from more intensified antiplatelet regimen. Additional clinical risk factor assessment rather than isolated platelet function-guided approaches should be investigated in future to evaluate personalized antiplatelet therapy in stable CAD-patients

GPla Polymorphisms Are Associated with Outcomes in Patients at High Cardiovascular Risk

BackgroundPlatelet membrane glycoprotein receptors mediate thrombus formation. GP Ia/IIa is an essential platelet integrin receptor. Single-nucleotide polymorphisms (SNPs) of the GP Ia/IIa gene alter GP Ia/IIa expression; however, their influence on cardiovascular disease remains unclear. This study aimed to investigate the effect of the GP Ia/IIa SNPs rs1126643 and rs1062535 on clinical outcomes in a large collective including high-risk patients with cardiovascular disease.Methods and resultsGP Ia SNP analysis was performed in 943 patients with symptomatic coronary artery disease. All patients were tracked for all-cause death, myocardial infarction, and ischemic stroke for 360 days. Homozygous carriers of the minor allele showed significantly worse event-free survival when compared with major allele carriers in the complete collective as well as in the subset of high-risk patients (carrying all of the following three risk factors: diabetes type II, hypertension, and hyperlipidemia). There was no significant difference in the subset of low-risk patients (carrying none of the three risk factors).ConclusionsGPla SNPs are associated with cardiovascular prognosis especially in high-risk patients. Identification of GPIa SNPs is of importance to tailor therapies in patients at already high cardiovascular risk

Variants of PEAR1 Are Associated With Outcome in Patients With ACS and Stable CAD Undergoing PCI

Introduction: Platelet endothelial aggregation receptor 1 (PEAR1) triggers platelet aggregation and is expressed in platelets and endothelial cells. Genome-wide association studies (GWAS) showed an association between platelet function and single-nucleotide polymorphisms (SNPs) in PEAR1.Methods: In 582 consecutive patients with stable coronary artery disease (CAD) or acute coronary syndrome (ACS) scheduled for PCI and treated with ASA and Clopidogrel, Prasugrel, or Ticagrelor, SNP analysis for rs12566888, rs2768759, rs41273215, rs3737224, and rs822442 was performed. During a follow-up period of 365 days after initial PCI, all patients were tracked for a primary endpoint, defined as a combined endpoint consisting of either time to death, myocardial infarction (MI) or ischemic stroke. All cause mortality, MI and ischemic stroke were defined as secondary endpoints.Results: Multivariable Cox model analysis for the primary endpoint revealed a significantly increased risk in homozygous PEAR1 rs2768759 minor allele carriers (hazard ratio, 3.16; 95% confidence interval, 1.4–7.13, p = 0.006). Moreover, PEAR1 rs12566888 minor allele carriers also showed an increased risk in all patients (hazard ratio, 1.69; 95% confidence interval, 0.87–3.27, p = 0.122), which was marginally significant in male patients (hazard ratio, 2.12; 95% confidence interval, 1.02–4.43, p = 0.045; n = 425).Conclusions: To the best of our knowledge, this is the first study showing that distinct genetic variants of PEAR1 are associated with cardiovascular prognosis in high risk patients undergoing PCI and treated with dual anti platelet therapy

Evaluation of clinical risk factors to predict high on-treatment platelet reactivity and outcome in patients with stable coronary artery disease (PREDICT-STABLE).

This study was designed to identify the multivariate effect of clinical risk factors on high on-treatment platelet reactivity (HPR) and 12 months major adverse events (MACE) under treatment with aspirin and clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI).739 consecutive patients with stable coronary artery disease (CAD) undergoing PCI were recruited. On-treatment platelet aggregation was tested by light transmittance aggregometry. Clinical risk factors and MACE during one-year follow-up were recorded. An independent population of 591 patients served as validation cohort.Degree of on-treatment platelet aggregation was influenced by different clinical risk factors. In multivariate regression analysis older age, diabetes mellitus, elevated BMI, renal function and left ventricular ejection fraction were independent predictors of HPR. After weighing these variables according to their estimates in multivariate regression model, we developed a score to predict HPR in stable CAD patients undergoing elective PCI (PREDICT-STABLE Score, ranging 0-9). Patients with a high score were significantly more likely to develop MACE within one year of follow-up, 3.4% (score 0-3), 6.3% (score 4-6) and 10.3% (score 7-9); odds ratio 3.23, P=0.02 for score 7-9 vs. 0-3. This association was confirmed in the validation cohort.Variability of on-treatment platelet function and associated outcome is mainly influenced by clinical risk variables. Identification of high risk patients (e.g. with high PREDICT-STABLE score) might help to identify risk groups that benefit from more intensified antiplatelet regimen. Additional clinical risk factor assessment rather than isolated platelet function-guided approaches should be investigated in future to evaluate personalized antiplatelet therapy in stable CAD-patients

Platelet surface expression of SDF-1 is associated with clinical outcomes in the patients with cardiovascular disease

Platelet surface expression levels of stromal cell derived factor 1 (SDF-1) are elevated in acute coronary syndrome and associated with LVEF% improvement after myocardial infarction (MI). Platelet SDF-1 might facilitate thrombus formation and endomyocardial expression of SDF-1 is enhanced in inflammatory cardiomyopathy and positively correlates with myocardial fibrosis. The influence of platelet SDF-1 on outcome in the patients with symptomatic coronary artery disease (CAD) is to the best of our knowledge unknown. Blood samples of 608 consecutive CAD patients were collected during the percutaneous coronary intervention and analyzed for surface expression of SDF-1 by flow cytometry. The primary combined endpoint was defined as the composite of either MI, or ischemic stroke, or all-cause death. Secondary endpoints were defined as the aforementioned single events. The patients with baseline platelet SDF-1 levels above the third quartile showed a significantly worse cumulative event-free survival when compared to the patients with lower baseline SDF-1 levels (first to third quartile) (log rank 0.009 for primary combined endpoint and log rank 0.016 for secondary endpoint all-cause death). Multivariate Cox regression analysis showed that SDF-1 levels above the third quartile were independently associated with the primary combined endpoint and the secondary endpoint all-cause death. We provide first clinical evidence that high platelet expression levels of SDF-1 influence clinical outcomes in CAD patients in a negative way