The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions 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

BIO101 in Sarcopenic Seniors at Risk of Mobility Disability: Results of a Double‐Blind Randomised Interventional Phase 2b Trial

ABSTRACT Background Sarcopenia is a progressive muscle disorder that may lead to mobility disability. No pharmaceutical interventions are currently available, and treatment relies on physical exercise and nutrition. The aim of SARA‐INT was to investigate whether BIO101 (20‐hydroxyecdysone), an activator of the MAS receptor, is safe and improves muscle function and physical performance of community dwelling older sarcopenic patients. Methods SARA‐INT was a randomised three‐arm interventional study (BIO101 175 mg bid /350 mg bid/placebo) with a planned 6‐month treatment (up to 9 months in 50 subjects). Eligibility criteria for sarcopenia were meeting FNIH criteria for sarcopenia and Short Physical Performance Battery (SPPB) score ≤ 8/12 in men and women aged ≥ 65 years. Primary endpoint was the change from baseline (CFB) in gait speed (GS) measured by 400‐m walking test (400MWT), secondary endpoints being CFB in other physical performance tests. Results A total of 233 participants were randomised (mean age 75.5 ± 7.12; 54.3% female), of whom 232 and 156 were included in the full analysis set (FAS) and per‐protocol (PP) populations, respectively. Due to COVID‐19 pandemic, 55% of on‐site end‐of‐treatment efficacy assessments were lost, reducing the studies' power. In the primary analysis (mix of 6/9 months), BIO101 350 mg bid treatment after 6/9 months was associated with an improvement in the 400MWT of 0.07 m/s versus placebo in the FAS population (not significant) and of 0.09 m/s in the PP population (p = 0.008). BIO101 350 mg bid treatment effect on the 400MWT GS was also observed in pre‐defined subpopulations at higher risk of mobility disability (0.0474 m/s for slow walkers, 0.0521 m/s for obese and 0.0662 m/s for chair stand sub‐score ≤ 2 from SPPB in the FAS population), with a trend for a dose response. BIO101 showed a good safety profile at both doses (number of subjects with related treatment emergent adverse events (TEAEs) of 13 (16.0%), 10 (13.3%) and 10 (13.5%) in the placebo, 175 mg and 350 mg BIO101 groups, respectively). Conclusions After 6 to 9 months of treatment, BIO101 350 mg bid showed strong trends consistent with a clinically relevant effect on the 400MWT GS, close to the minimal clinically important difference (MCID) in sarcopenia (0.1 m/s). This was also shown in predefined subpopulations at higher risk of mobility disability. BIO101 showed a good safety profile. Taken together, efficacy and safety data of this Phase 2 trial encourage us to pursue further development of BIO101 for the treatment of sarcopenia

Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension

AbstractAfter demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%–73%) and decreased with nebivolol (51%–65%) and the combination treatment (17%–39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%–22%; nebivolol, 20%–26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further