No abstract

The role of alpha- and beta-adrenoceptors in the development of catecholamine-induced cardiac hypertrophy in vivo was investigated. Rats received a constant intravenous infusion of norepinephrine or sodium chloride (control) for 3 days. The norepinephrine infusion was combined with the alpha-blocker prazosin, the beta-blocker metoprolol, or both blockers. For modulation of the work load of the heart, the calcium channel blocker verapamil was added to the norepinephrine infusion. A further group of animals was treated with the alpha-adrenergic stimulator norfenephrine, which also was combined with prazosin or verapamil. Norepinephrine induced significant increases in mean aortic pressure, left ventricular dP/dtmax, heart rate, and total peripheral resistance. The left ventricular weight/body weight ratio was significantly elevated and was accompanied by an increase in the RNA concentration and the RNA/DNA ratio. Prazosin as well as metoprolol partially antagonized the increase in left ventricular weight and RNA concentration, whereas simultaneous prazosin and metoprolol treatment prevented the norepinephrine-induced alterations. Although combination of norepinephrine with verapamil resulted in considerable reduction of all functional parameters, the development of cardiac hypertrophy and the elevated RNA/DNA ratio were not significantly influenced. Stimulation of alpha-receptors with norfenephrine elicited an increase in total peripheral resistance and in left ventricular weight, which was abolished by prazosin. Verapamil did not affect the norfenephrine-induced cardiac hypertrophy, although it normalized essentially all functional parameters. Thus, the rapid development of cardiac hypertrophy in the norepinephrine model seems to be directly mediated by stimulation of myocardial alpha- and beta-adrenoceptors rather than by hemodynamic changes.

The ENTRUST-AF PCI trial tests the hypothesis that an edoxaban-based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual-antiplatelet therapy in patients with AF in need of oral anticoagulation. The relative risk of ischemic events between groups will be compared.

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Aim Non-vitamin K oral anticoagulants (NOACs) are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of edoxaban in routine care are limited in Europe. We report one-year outcomes in patients with AF treated with edoxaban in routine care. Methods and results ETNA-AF-Europe is a prospective, multi-centre, post-authorisation, observational study enrolling patients treated with edoxaban in 10 European countries, the design of which was agreed with the European Medicines Agency as part of edoxaban’s post-approval safety plan. Altogether 13,092 patients in 852 sites completed the one-year follow-up (mean age: 73.6 ± 9.5 years; 57% male, mean follow-up: 352 ± 49 days [median: 366 days]). Most patients had associated comorbidities (mean CHA2DS2-VASc score: 3.1 ± 1.4). Stroke or systemic embolism was reported in 103 patients (annualised event rate: 0.82%/year), and major bleeding events was reported in 132 patients (1.05%/year). Rates of intracranial haemorrhage were low (30 patients [0.24%/year]). Death occurred in 442 patients (3.50%/year); cardiovascular death occurred in 206 patients (1.63%/year). The approved dosing of edoxaban was chosen in 83%. All-cause and cardiovascular mortality were higher in patients receiving edoxaban 30 mg versus 60 mg, in line with the higher age and more frequent comorbidities of the 30 mg group. Major bleeding was also numerically more common in patients receiving edoxaban 30 mg versus 60 mg. Conclusion The rates of stroke, systemic embolism and major bleeding are low in this large unselected cohort of high-risk AF patients routinely treated with edoxaban.