We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI.
Methods Between Aug 26, 2010, and July 7, 2011, 200 patients were enrolled into our prospective, randomised, proof-of-concept study. Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2
allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 selleck screening library carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment, which is a marker associated with increased adverse cardiovascular events. Interventional cardiologists and data analysts were masked to genetic status and treatment. Patients were not masked to
treatment allocation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, NCT01184300.
Findings After randomisation, 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0.0092). The point-of-care genetic test had a this website sensitivity of 100% (95% CI 92.3-100) and a specificity of 99.3% (96.3-100).
Interpretation
Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity.”
“Objective: To examine whether dysregulation MLN2238 of the hypothalamic-pituitary-adrenal (HPA) axis associated with disadvantaged social position in working populations also occurs in older age groups. Methods: This study examines the association of several indicators of social position with two measures of cortisol secretion, a product of the HPA axis. We examined the cortisol awakening response (CAR), and slope of the decline in cortisol secretion across the day. We examine whether the association is mediated by behavioral, psychosocial, and biological factors in 3992 participants of phase 7 (2002-2004) of the Whitehall 11 study, who provided six salivary cortisol samples across the day. Results: In this older cohort (mean age = 61 years; range = 50-74 years), lowest social position (assessed by current or previous occupational grade and wealth) was associated with a flatter slope in the decline in cortisol secretion.