Inadequate heart rate control despite widespread use of beta-blockers in outpatients with stable CAD: findings from the international prospective CLARIFY registry

Background: To use CLARIFY, a prospective registry of patients with stable CAD (45 countries), to explore heart rate (HR) control and beta-blocker use.<p></p> Methods: We analyzed the CLARIFY population according to beta-blocker use via descriptive statistics with Pearson's χ2 test for comparisons, as well as a multivariable stepwise model.<p></p> Results: Data on beta-blocker use was available for 32,914 patients, in whom HR was 68 ± 11 bpm; patients with angina, previous myocardial infarction, and heart failure had HRs of 69 ± 12, 68 ± 11, and 70 ± 12 bpm, respectively. 75% of these patients were receiving beta-blockers. Bisoprolol (34%), metoprolol tartrate (16%) or succinate (13%), atenolol (15%), and carvedilol (12%) were mostly used; mean dosages were 49%, 76%, 35%, 53%, and 45% of maximum doses, respectively. Patients aged < 65 years were more likely to receive beta-blockers than patients ≥ 75 years (P < 0.0001). Gender had no effect. Subjects with HR ≤ 60 bpm were more likely to be on beta-blockers than patients with HR ≥ 70 bpm (P < 0.0001). Patients with angina, previous myocardial infarction, heart failure, and hypertension were more frequently receiving beta-blockers (all P < 0.0001), and those with PAD and asthma/COPD less frequently (both P < 0.0001). Beta-blocker use varied according to geographical region (from 87% to 67%).<p></p> Conclusions: Three-quarters of patients with stable CAD receive beta-blockers. Even so, HR is insufficiently controlled in many patients, despite recent guidelines for the management of CAD. There is still much room for improvement in HR control in the management of stable CAD

Relationships between components of blood pressure and cardiovascular events in patients with stable coronary artery disease and hypertension

Observational studies have shown a J-shaped relationship between diastolic blood pressure (BP) and cardiovascular events in hypertensive patients with coronary artery disease. We investigated whether the increased risk associated with low diastolic BP reflects elevated pulse pressure (PP). In 22 672 hypertensive patients with coronary artery disease from the CLARIFY registry (Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease), followed for a median of 5.0 years, BP was measured annually and averaged. The relationships between PP and diastolic BP, alone or combined, and the primary composite outcome (cardiovascular death or myocardial infarction) were analyzed using multivariable Cox proportional hazards models. Adjusted hazard ratios for the primary outcome were 1.62 (95% confidence interval [CI], 1.40–1.87), 1.00 (ref), 1.07 (95% CI, 0.94–1.21), 1.54 (95% CI, 1.32–1.79), and 2.34 (95% CI, 1.95–2.81) for PP<45, 45 to 54 (reference), 55 to 64, 65 to 74, and ≥75 mm Hg, respectively, and 1.50 (95% CI, 1.31–1.72), 1.00 (reference), and 1.58 (95% CI, 1.42–1.77) for diastolic BPs of <70, 70 to 79 (ref), and ≥80 mm Hg, respectively. In a cross-classification analysis between diastolic BP and PP, the relationship between diastolic BP and the primary outcome remained J-shaped when the analysis was restricted to patients with the lowest-risk PP (45–64 mm Hg), with adjusted hazard ratios of 1.53 (95% CI, 1.27–1.83), 1.00 (ref), and 1.54 (95% CI, 1.34–1.75) in the <70, 70 to 79 (reference), and ≥80 mm Hg subgroups, respectively. The J-shaped relationship between diastolic BP and cardiovascular events in hypertensive patients with coronary artery disease persists in patients within the lowest-risk PP range and is therefore unlikely to be solely the consequence of an increased PP reflecting advanced vascular disease

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

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

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

Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.)