Clinical Significance of Laboratory-determined Aspirin Poor Responsiveness After Primary Percutaneous Coronary Intervention.

AIMS: The objective of the present substudy was to examine whether aspirin poor/high responsiveness (APR/AHR) is associated with increased rates of major adverse cardiovascular events (MACE) and serious bleeding after primary percutaneous coronary intervention (PPCI). METHODS: We analyzed 961 consecutive ST-elevation acute myocardial infarction patients who underwent PPCI between February 2008 and June 2011. Multiplate analyser (Dynabite, Munich, Germany) was used for the assessment of platelet reactivity. APR/AHR were defined as the upper/lower quintiles of ASPI values, determined 24 h after aspirin loading. APR patients were tailored using 300 mg maintenance dose for 30 days. The co-primary end points at 30 days were: MACE (death, non-fatal infarction, ischemia-driven target vessel revascularization and ischemic stroke) and serious bleeding according to the BARC classification. RESULTS: One hundred and 90 patients were classified as APR, and 193 patients as AHR. At admission, compared with aspirin sensitive patients (ASP), patients with APR had more frequently diabetes, anterior infarction and heart failure, while AHR patients had reduced values of creatine kinase, leukocytes, heart rate and systolic blood pressure. Compared with ASP, the rates of 30-day primary end points did not differ neither in APR group including tailored patients (MACE, adjusted OR 1.02, 95%CI 0.47-2.17; serious bleeding, adjusted OR 1.92, 95%CI 0.79-4.63), nor in patients with AHR (MACE, adjusted OR 1.58, 95%CI 0.71-5.51; serious bleeding, adjusted OR 0.69, 95%CI 0.22-2.12). CONCLUSIONS: The majority of APR patients were suitable for tailoring. Neither APR including tailored patients nor AHR were associated with adverse 30-day efficacy or safety clinical outcomes.

Low On-Treatment Platelet Reactivity Predicts Long-Term Risk of Bleeding After Elective PCI.

BACKGROUND: Bleeding after percutaneous coronary interventions (PCI) is an important complication with impact on prognosis. AIM: To evaluate the predictive value of enhanced platelet responsiveness to dual antiplatelet therapy with aspirin and clopidogrel, for bleeding, after elective PCI. METHODS AND RESULTS: We performed multiple electrode aggregometry (MAE) platelet functional tests induced by arachidonic acid (ASPI) and adenosine-diphosphate (ADP) before PCI, and 24 hours after PCI, in 481 elective PCI patients who were followed-up for an average of 15.34 ± 7.19 months. Primary end point was the occurrence of any bleeding, while ischemic major adverse cardiovascular event (MACE) was a secondary endpoint. The incidence of total, BARC ≤ 2, and BARC ≥ 3 bleeding, according to BARC classification, was 19, 18, and 1%, respectively. Groups with any, and BARC ≤ 2 bleeding, had a lower average value of MAE ADP test after 24 hours, compared to the group without bleeding: 45.30 ± 18.63 U versus 50.99 ± 19.01 U; P = 0.005; and 45.75 ± 18.96 U versus 50.99 ± 18.99 U; P = 0.01; respectively. Female gender (HR 2.11; CI 1.37-3.25; P = 0.001), previous myocardial infarction (HR 0.56; CI 0.37-0.85; P = 0.006), lower body mass (HR 0.78; CI 0.62-0.98; P = 0.03), and MAE ADP test after 24 hours (HR 0.75; CI 0.61-0.93; P = 0.009) were the independent predictors for any bleeding by Cox univariate analysis. After adjustment, MAE ADP test after 24 hours, was the only independent predictor for any (HR 0.7; CI 0.56-0.87; P = 0.002), and BARC ≤ 2 (HR 0.71; CI 0.56-0.89; P = 0.003) bleeding, by Cox multivariate analysis. CONCLUSION: MAE ADP test before and after PCI, was associated with any, and BARC ≤ 2 bleeding after elective PCI.

PCI and clopidogrel: antiplatelet responsiveness and patient characteristics.

OBJECTIVE: This study on responsiveness to clopidogrel and aspirin evaluates its interaction with: (i) patient characteristics; (ii) procedure characteristics; (iii) antiplatelet dose. METHODS AND RESULTS: After elective PCI, 60 patients receiving aspirin 100 mg daily, and clopidogrel 75 mg daily were monitored with the PFA 100 test and VASP assay. Non-responsiveness to aspirin and clopidogrel was found in 23 (38%) and 18 (30%) of 60 patients, respectively. Seven (12%) patients were dual nonresponders. Non-responders to both aspirin and clopidogrel were more often smokers. Non-responders to clopidogrel, in addition had elevated inflammatory markers (P < 0.05). Dual non-responders had (i) a higher platelet count, LDL, and CRP; (ii) a lower HDL (P < 0.05). Clopidogrel non-responders were receiving 150 mg clopidogrel, with a positive response in 72%. Eighty % of non-responders to 150 mg clopidogrel were also non-responders to aspirin. CONCLUSION: Baseline patient characteristics and clopidogrel dose modify the antiplatelet response. Also, patients resistant to both aspirin and clopidogrel do no benefit from an increased clopidogrel dose.

Velocity propagation of early diastole is a valuable tool for left ventricular remodelling after the first myocardial infarction.

PURPOSE: Velocity propagation (Vp) of early diastole is a known method for the evaluation of left ventricular (LV) diastolic function. Our purpose was to determine whether Vp is a valuable tool to characterize patients after acute myocardial infarction and LV remodelling (LVR). METHODS: M-mode, two-dimensional and Doppler echocardiography were performed in 71 patients within the first 2 days, 1, 3 and 6 months after acute myocardial infarction. We measured the left atrium, LV diameters and volumes, peak early and late velocity (E, A) deceleration time, Vp, annular velocity (e) and calculated E/e. The patients were divided in two groups: (A) without early LVR (n=39) and (B) with early LVR (n=32). RESULTS: In the first evaluation, Vp was similar in both groups (36.37 vs. 35.49 cm/s, P=0.513). Late LVR (LLVR) (44%) had developed in patients from group A with significantly lower early Vp compared with patients without LLVR (31.52 vs. 40.12 cm/s, P=0.001), with persist values even after 6 months (29.41 vs. 40.85 cm/s, P=0.001). The values of Vp were similar in the first 2 days in patients from group B with developing (78%) and nondeveloping LLVR (35.29 vs. 36.60 cm/s, P=0.614). Differences became significant after 6 months (31.71 vs. 41.80 cm/s, P=0.001). The values of Vp of 35 cm/s or less from the first week in both groups correlated with LLVR (B=3.27, P=0.015). Changing of LV volumes significantly correlated with Vp; for end-diastolic volume/body surface area (r=0.21, P=0.041) and end-systolic volume/body surface area (r=0.30, P=0.014). CONCLUSION: In this study, Vp was the only valuable Doppler echocardiographic tool that reflected early LVR and LLVR.

The pharmacokinetics of Biolimus A9 after elution from the Nobori stent in patients with coronary artery disease: the NOBORI PK study.

OBJECTIVES: The aim of this study was to assess the pharmacokinetics and tolerability of Biolimus A9 eluted from Nobori coronary stents. BACKGROUND: : The release kinetics and pharmacokinetics of drugs delivered via coronary stents have been shown to play an essential role in the efficacy and safety of drug eluting stents. METHODS: Twenty patients with coronary artery disease were treated with single 14-mm (10 patients) or 28-mm long stent (10 patients). Blood samples were drawn at 16 time points to determine the pharmacokinetics of Biolimus A9. At seven time points, complete laboratory and toxicology panels were assessed to screen for potential Biolimus A9 toxicity. The primary endpoint of the study was the systemic blood concentrations of Biolimus A9 after 28 days and 6 months as measured using highly specific and sensitive liquid chromatography- tandem mass spectrometry assay. RESULTS: At 28 days, 6 patients (30%) had quantifiable Biolimus A9 concentrations in blood. The highest Biolimus A9 blood concentration measured in any sample was 32.2 pg/mL. The median time to maximum concentration was 2 hr, ranging from 0.05 hr to 3 months. Six months after stent implantation, only 1 of 20 patients had measurable Biolimus A9 concentrations at the lowest level of quantification, while at 9 months no sample had quantifiable Biolimus A9 concentrations. Laboratory and toxicology assessments did not indicate any impact of Biolimus A9 on the evaluated parameters. CONCLUSION: Results of this study suggest that systemic exposure to Biolimus A9 was very low and that Biolimus A9 was well tolerated.