Metabolism of ticagrelor in patients with acute coronary syndromes.

© The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio

Contrasting the beam interaction characteristics of selected lasers with a partially stabilised zirconia (PSZ) bio-ceramic

Differences in the beam interaction characteristics of a CO2 laser, a Nd:YAG laser, a high power diode laser (HPDL) and an excimer laser with a partially stabilised zirconia (PSZ) bio-ceramic have been studied. A derivative of Beer-Lambert’s law was applied and the laser beam absorption lengths of the four lasers were calculated as 33.55 x 10-3 cm for the CO2 laser, 18.22 x 10-3 cm for the Nd:YAG laser, 17.17 x 10-3 cm for the HPDL and 8.41 x 10-6 cm for the excimer laser. It was determined graphically that the fluence threshold values at which significant material removal was effected by the CO2 laser, the Nd:YAG laser, the HPDL and the excimer laser were 52 J/cm2, 97 J/cm2, 115 J/cm2 and 0.48 J/cm2 respectively. The thermal loading value for the CO2 laser, the Nd:YAG laser, the HPDL and the excimer laser were calculated as being 1.55 kJ/cm3, 5.32 kJ/cm3, 6.69 kJ/cm3 and 57.04 kJ/cm3 respectively

Intervention in acute coronary syndromes:do patients undergo intervention on the basis of their risk characteristics? The Global Registry of Acute Coronary Events (GRACE)

OBJECTIVE: To determine whether revascularisation is more likely to be performed in higher-risk patients and whether the findings are influenced by hospitals adopting more or less aggressive revascularisation strategies. METHODS: GRACE (Global Registry of Acute Coronary Events) is a multinational, observational cohort study. This study involved 24,189 patients enrolled at 73 hospitals with on-site angiographic facilities. RESULTS: Overall, 32.5% of patients with a non-ST elevation acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI; 53.7% in ST segment elevation myocardial infarction (STEMI)) and 7.2% underwent coronary artery bypass grafting (CABG; 4.0% in STEMI). The cumulative rate of in-hospital death rose correspondingly with the GRACE risk score (variables: age, Killip class, systolic blood pressure, ST segment deviation, cardiac arrest at admission, serum creatinine, raised cardiac markers, heart rate), from 1.2% in low-risk to 3.3% in medium-risk and 13.0% in high-risk patients (c statistic = 0.83). PCI procedures were more likely to be performed in low- (40% non-STEMI, 60% STEMI) than medium- (35%, 54%) or high-risk patients (25%, 41%). No such gradient was apparent for patients undergoing CABG. These findings were seen in STEMI and non-ST elevation ACS, in all geographical regions and irrespective of whether hospitals adopted low (4.2-33.7%, n = 7210 observations), medium (35.7-51.4%, n = 7913 observations) or high rates (52.6-77.0%, n = 8942 observations) of intervention. CONCLUSIONS: A risk-averse strategy to angiography appears to be widely adopted. Proceeding to PCI relates to referral practice and angiographic findings rather than the patient\u27s risk status. Systematic and accurate risk stratification may allow higher-risk patients to be selected for revascularisation procedures, in contrast to current international practice

Buildings behaving badly:A behavioral experiment on how different motivational frames influence residential energy label adoption in the Netherlands

Heating buildings contributes to approximately 36% of Europe’s energy demand and several EU member states have adopted mandatory energy labels to improve energy efficiency by promoting home weatherization investments. This paper focuses on the perception of the energy label for residential buildings in the Netherlands and the role of different frames (egoistic, biospheric and social norms and neutral frames) in motivating adoption of energy labels for housing. We used a behavioral email experiment and an online survey to investigate these motivational factors. We find that biospheric frames are weaker than the other three motivational frames in terms of engaging interest in the energy label, but that the biospheric frame results in higher willingness to pay (WTP) for the energy label. We also find that age (rather than income) correlates with higher willingness to pay for home energy labels

Predictors, type, and impact of bleeding on the net clinical benefit of long-term ticagrelor in stable patients with prior myocardial infarction

BACKGROUND: Ticagrelor reduces ischemic risk but increases bleeding in patients with prior myocardial infarction. Identification of patients at lower bleeding risk is important in selecting patients who are likely to derive more favorable outcomes versus risk from this strategy. METHODS AND RESULTS: PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis in Myocardial Infarction 54) randomized 21 162 patients with prior myocardial infarction in a 1:1:1 fashion to ticagrelor 60 mg or 90 mg twice daily or placebo, with ticagrelor 60 mg approved for long-term use. TIMI major or minor bleeding was the primary end point for this analysis. Causes of bleeding were categorized by site and etiology, and independent predictors were identified. At 3 years, ticagrelor 60 mg increased the rate of TIMI major or minor bleeding by 2.0% versus placebo (1.4% placebo versus 3.4% ticagrelor). The bleeding excess was driven primarily by spontaneous gastrointestinal bleeds. A history of spontaneous bleeding requiring hospitalization and the presence of anemia were independent predictors of bleeding but not of ischemic risk. Patients with at least 1 risk predictor had 3-fold higher rates of bleeding with ticagre-lor 60 mg versus those who had neither (absolute risk increase, 4.4% versus 1.5%; P=0.01). Patients with neither predictor had a more favorable benefit profile with ticagrelor 60 mg versus placebo including lower mortality (hazard ratio, 0.79; 95% CI, 0.65–0.96; P interaction = 0.03). CONCLUSIONS: In patients with prior myocardial infarction, bleeding with ticagrelor 60 mg twice daily is predominantly spontaneous gastrointestinal. A history of spontaneous bleeding requiring hospitalization or the presence of anemia identifies patients at higher risk of bleeding, and the absence of either identifies patients likely to have a more favorable net benefit with ticagrelor

Wettability characteristics of an Al2O3/SiO2-based ceramic modified with CO2, Nd:YAG, excimer and high-power diode lasers

Interaction of CO2, Nd:YAG, excimer and high power diode laser (HPDL) radiation with the surface of an Al2O3/SiO2 based ceramic was found to effect significant changes in the wettability characteristics of the material. It was observed that interaction with CO2, Nd:YAG and HPDL radiation reduced the enamel contact angle from 1180 to 310, 340 and 330 respectively. In contrast, interaction with excimer laser radiation resulted an increase in the contact angle to 1210. Such changes were identified as being due to: (i) the melting and partial vitrification of the Al2O3/SiO2 based ceramic surface as a result of interaction with CO2, Nd:YAG HPDL radiation. (ii) the surface roughness of the Al2O3/SiO2 based ceramic increasing after interaction with excimer laser radiation. (iii) the surface oxygen content of the Al2O3/SiO2 based ceramic increasing after interaction with CO2, Nd:YAG and HPDL radiation. The work has shown that the wettability characteristics of the Al2O3/SiO2 based ceramic could be controlled and/or modified with laser surface treatment. In particular, whether the laser radiation had the propensity to cause surface melting. However, a wavelength dependance of the change of the wetting properties could not be deduced from the findings of this work

β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study

Objective: To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction. Design: Multicentre prospective cohort study. Setting: Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005. Participants: 2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction. Main outcome measures: Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use. Results: β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results. Conclusions: Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction. Trial registration: Clinical trials NCT00673036

Excess risk attributable to traditional cardiovascular risk factors in clinical practice settings across Europe - The EURIKA Study

<p>Abstract</p> <p>Background</p> <p>Physicians involved in primary prevention are key players in CVD risk control strategies, but the expected reduction in CVD risk that would be obtained if all patients attending primary care had their risk factors controlled according to current guidelines is unknown. The objective of this study was to estimate the excess risk attributable, firstly, to the presence of CVD risk factors and, secondly, to the lack of control of these risk factors in primary prevention care across Europe.</p> <p>Methods</p> <p>Cross-sectional study using data from the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA), which involved primary care and outpatient clinics involved in primary prevention from 12 European countries between May 2009 and January 2010. We enrolled 7,434 patients over 50 years old with at least one cardiovascular risk factor but without CVD and calculated their 10-year risk of CVD death according to the SCORE equation, modified to take diabetes risk into account.</p> <p>Results</p> <p>The average 10-year risk of CVD death in study participants (N = 7,434) was 8.2%. Hypertension, hyperlipidemia, smoking, and diabetes were responsible for 32.7 (95% confidence interval 32.0-33.4), 15.1 (14.8-15.4), 10.4 (9.9-11.0), and 16.4% (15.6-17.2) of CVD risk, respectively. The four risk factors accounted for 57.7% (57.0-58.4) of CVD risk, representing a 10-year excess risk of CVD death of 5.66% (5.47-5.85). Lack of control of hypertension, hyperlipidemia, smoking, and diabetes were responsible for 8.8 (8.3-9.3), 10.6 (10.3-10.9), 10.4 (9.9-11.0), and 3.1% (2.8-3.4) of CVD risk, respectively. Lack of control of the four risk factors accounted for 29.2% (28.5-29.8) of CVD risk, representing a 10-year excess risk of CVD death of 3.12% (2.97-3.27).</p> <p>Conclusions</p> <p>Lack of control of CVD risk factors was responsible for almost 30% of the risk of CVD death among patients participating in the EURIKA Study.</p