The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

In several conditions associated with adrenergic stimulation, an increase in peripheral count of larger platelets has been observed, but the mechanism remained elusive. Larger platelets have greater prothrombotic potential and increase the risk of acute thrombotic events. The human spleen retains one-third of total body platelets, with mean volume (MPV) about 20% greater than that of circulating platelets. We aimed to answer whether low-dose epinephrine infusion results in spleen contraction and MPV increase. We undertook the continuous ultrasonic measurements of spleen volume, hepatic and central circulation with concurrent blood sampling in response to intravenous infusion of epinephrine (6 min of 0·06 µg kg(-1) per min, followed by 3 min of 0·12 µg kg(-1) per min) in nine healthy young subjects. The spleen volume started to decrease immediately after the onset of infusion, in the presence of substantial decreases in peripheral resistance and mean blood pressure and increases in heart rate and cardiac output. The majority of spleen emptying, approximately 25%, (95% CI 71·3-299·7) was observed 1 min after infusion onset, the hepatic vein flow peaked at the end of infusion for 28·4% (95% CI 1074·6-407·9), while increases in platelet count for approximately 31% (95% CI 187·8-314·8) and MPV for 4·4% (95% CI 7·3-10·9) lagged until 1 min after infusion cessation. We suggest that spleen is a dynamic reservoir of large platelets, which are mobilized even by low-dose epinephrine infusion in conditions of decreased blood pressure.

1. The spleen contains approximately one-third of all the body's platelets. These platelets are relatively larger and haemostatically more active than platelets in the systemic circulation and can be released into the systemic circulation by stimulation of alpha-adrenoceptors or inhibition of beta-adrenoceptors. In the present study, we evaluated the effects of selective (bisoprol) and non-selective (carvedilol) beta-blockers agents on mean platelet volume (MPV) and spleen size in hypertensive patients at rest and after exercise. 2. Blood pressure, heart rate, platelet count, MPV and spleen volume were measured in 18 newly diagnosed hypertensive patients, as well as in nine healthy control subjects, subjected to treadmill exercise test at their first visit and, for the hypertensive group, after 15 and 30 days of treatment with the selective beta(1)-adrenoceptor antagonist bisoprolol 5 mg/day (n = 9) or the non-selective alpha(1)-, beta(1)- and beta(2)-adrenoceptor antagonist carvedilol 25 mg/day (n = 9). 3. Increases in resting MPV values with concomitant decreases in spleen volume were found after 15 and 30 days treatment with either bisoprolol or carvedilol. The pronounced decrease in splenic volume after exercise and the increased MPV and platelet counts seen at first visit were halved after 15 and 30 days of treatment with either drug. 4. We conclude that in hypertensive patients treated with either selective or non-selective beta-blockers, the spleen contracts and MPV increases, which may increase the risk of atherothrombosis.

Background and purpose Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013. Graphical abstract

Background: Nausea and vomiting are well-known gastrointestinal complications in chronic renal failure and are frequent indications for the commencement of dialysis. Although the administration of antiemetic drugs (metoclopramide and, recently, ondansetron) is usually mentioned, there are scanty data on their effects. Methods: A double-blind crossover study was done in 10 uremic patients. All the patients were uremic and suffered from nausea and vomiting. The drugs were randomly administered intravenously (either metoclopramide 10 mg or ondansetron 8 mg) 2 h after blood drawing for laboratory tests either on the 1st or on the 3rd study day at the same time. The outcomes were scored after 24 h of follow-up by (1) one of us (D.P.; 1–3 points: 1 = no effect; 2 = moderate effect – decreased frequency of vomiting, and 3 = good effect – no vomiting), and (2) by the patients (1–5 points). Results: The results obtained showed that ondansetron was more effective in controlling nausea and vomiting than metoclopramide, either objectively (2.80 ± 0.422 vs. 1.40 ± 0.699, p < 0.005) or subjectively (4.10 ± 0.738 vs. 2.10 ± 0.994, p < 0.005). Conclusions: We conclude that at the dosage level studied ondansetron is about twice as effective as metoclopramide in the symptomatic relief of uremia-induced nausea and vomiting.