Twenty-four-hour time dependency of clopidogrel effects in patients with acute coronary syndromes: The CiCAD-Study.

Long-term evidence shows an increased risk of cardiovascular events in the morning hours and recent studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Similar pharmacodynamic analyses of adenosine-diphosphate (ADP) receptor inhibitors are scarce. We therefore investigated changes in clopidogrel-dependent platelet function and activation over 24 h and whether enhanced platelet turnover might explain diurnal variability of platelet function and activation. Twenty-one patients after acute coronary syndromes (ACS) on maintenance doses of clopidogrel (75 mg) and aspirin (100 mg) Once per day (OD) were included. Blood was collected at five time points in 24 h. Platelet function and activation was analyzed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P), Verify Now, multiple electrode aggregometry (MEA), and platelet PAC-1 and P-selectin (P-sel) expression. Additionally, platelet count, mean platelet volume (MPV), and reticulated platelet fraction (RPF) were analyzed. There was significant diurnal variability of clopidogrel effects as documented with VASP-P, Verify Now, and PAC-1 and P-sel (all p < 0.05), whereas MEA did not differ over 24 h. Neither MPV nor RPF varied significantly over 24 h. In patients with high RPF, platelet function and activation was significantly higher in all assays, compared to patients with low RPF (all p < 0.05). However, the changes over time in low versus high RPF groups were similar. ADP-dependent platelet function and activation recovers significantly at the end of the 24-h dosing interval in patients with ACS on a maintenance dose of clopidogrel and aspirin. Although platelet function and activation is increased in patients with higher RPF, platelet turnover might not explain the observed diurnal variability.

Usefulness of Elevated Levels of Growth Differentiation Factor-15 to Classify Patients With Acute Coronary Syndrome Having Percutaneous Coronary Intervention Who Would Benefit from High-Dose Statin Therapy.

The aim of this study was to evaluate whether growth differentiation factor-15 (GDF-15) plasma concentration at the time of percutaneous coronary intervention (PCI) might help identify those patients with acute coronary syndrome (ACS), who benefit most from high-dose statin treatment. Two hundred eighty-four consecutive patients, who underwent percutaneous coronary intervention (PCI) for ACS, were included in a prospective registry. The combined end point at 3 months after PCI consisted of cardiovascular death, nonfatal myocardial infarction, and unstable angina. Patients were divided into those with elevated levels of GDF-15 and those with lower levels in relation to the median plasma concentration. Results were compared between patients receiving high-dose, highly efficient statins and patients receiving low-dose statins or no statins. The median GDF-15 plasma concentration was 3.31 ng/ml. One hundred six patients (74.6%) of the high GDF-15 group and 122 patients (85.9%) of the low GDF-15 group received high-dose statins. The combined end point was statistically lower in patients with high levels of GDF-15 treated with high-dose statins compared with patients treated with low-dose statins or without statin treatment (3.8% vs 22.2%, hazard ratio [HR] = 0.156; 95% confidence interval [CI], 0.047 to 0.519; p = 0.002). After propensity score adjustment, the results remained significant (adjusted HR for high-dose statins = 0.148; 95% CI, 0.045 to 0.494; p = 0.002). In contrast, in patients with lower levels of GDF-15, there was no significant reduction in combined end point rates associated with high-dose statin treatment (1.6% vs 5.0%, HR = 0.320; 95% CI 0.029 to 3.534; p = 0.353). In conclusion, increased GDF-15 plasma concentrations at the time of PCI and stent implantation might classify high-risk patients with ACS who benefit from high-dose, highly efficient statins.

Contrast induced acute kidney injury in acute coronary syndrome patients: A single centre experience.

BACKGROUND: The aim of the study was to investigate predictors of contrast induced acute kidney injury, in-hospital and long-term mortality in patients with acute coronary syndrome treated by percutaneous coronary intervention. METHODS: We investigated 536 consecutive patients with acute coronary syndrome who underwent percutaneous coronary intervention. Contrast induced acute kidney injury was classified according to risk, injury, failure, loss of kidney function and end-stage kidney disease/acute kidney injury network (RIFLE/AKIN) criteria into those with normal kidney function, risk, RIFLE stage I and those with stage ⩾ II. We investigated in-hospital, all-cause mortality during index hospitalization and long-term all-cause mortality during the follow-up period of 94 months (interquartile 81.6-108.9 months) in adjustment with parameters of the Global Risk of Acute Coronary Events score. RESULTS: Patients with contrast induced acute kidney injury had worse baseline clinical characteristics and displayed more co-morbidities than patients with normal kidney function. In multivariate logistic regression analysis intra-aortic balloon pump use, congestive heart failure, age >75 years and admission serum creatinine >1.5mg/dl were independent predictors of contrast induced acute kidney injury development. contrast induced acute kidney injury RIFLE stage ⩾ II was an independent predictor of in-hospital mortality (odds ratio 33.16, confidence interval 1.426-770.79, p=0.029) and long-term mortality (hazard ratio 4.713, confidence interval 1.53-14.51, p=0.007) even after adjustment for confounders (variables of Global Risk of Acute Coronary Events score). CONCLUSION: Contrast induced acute kidney injury is a common complication of acute coronary syndrome patients treated by percutaneous coronary intervention. Advanced deterioration in renal function after percutaneous coronary intervention is an independent predictor for in-hospital and long-term mortality.