12 research outputs found

    Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

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    Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

    The Valvular Apparatus in Venous Insufficiency: A Problem of Quantity?

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    Abnormal venous valvular function may produce venous reflux and venous insufficiency. While valvular agenesis is a known, but rare cause of venous insufficiency. While valvular agenesis is a known, but rare cause of venous insufficiency, little work has been done on the relative number of greater saphenous vein (GSV) valves in patients with venous insufficiency. This study investigates whether the GSV in patients with symptomatic venous insufficiency has fewer valves than the GSV of patients without venous insufficiency. The number of GSV valves in patients (n = 51) with symptomatic venous insufficiency undergoing saphenectomy (VI) were compared with the number of GSV valves in patients (n = 26) without venous insufficiency undergoing in situ GSV bypass under angioscopic surveillance who served as a control group. The two groups differed, as expected, in age and sex distribution. The VI group had a mean of 25.7 ± 11.0 centimeters of GSV between valves, while the control group had 19.0 ± 9.7 centimeters of GSV between valves (F = 6.99; p = 0.01). The mean number of valves in the saphenous veins of the two groups also differed significantly: VI = 2.3 ± 0.83 versus control (CTRL) = 4.8 ± 2.01 (F = 61.86; p \u3c 0.0001). That properly functioning valve leaflets help maintain physiologic antegrade venous flow is indisputable. This study, however, suggests that the relative lack of valves may be related to the development of venous insufficiency. This report documents that patients with symptomatic reflux in the GSV have significantly fewer valves than patients with apparently normal functioning saphenous veins

    The Valvular Apparatus in Venous Insufficiency: A Problem of Quantity?

    No full text
    Abnormal venous valvular function may produce venous reflux and venous insufficiency. While valvular agenesis is a known, but rare cause of venous insufficiency. While valvular agenesis is a known, but rare cause of venous insufficiency, little work has been done on the relative number of greater saphenous vein (GSV) valves in patients with venous insufficiency. This study investigates whether the GSV in patients with symptomatic venous insufficiency has fewer valves than the GSV of patients without venous insufficiency. The number of GSV valves in patients (n = 51) with symptomatic venous insufficiency undergoing saphenectomy (VI) were compared with the number of GSV valves in patients (n = 26) without venous insufficiency undergoing in situ GSV bypass under angioscopic surveillance who served as a control group. The two groups differed, as expected, in age and sex distribution. The VI group had a mean of 25.7 ± 11.0 centimeters of GSV between valves, while the control group had 19.0 ± 9.7 centimeters of GSV between valves (F = 6.99; p = 0.01). The mean number of valves in the saphenous veins of the two groups also differed significantly: VI = 2.3 ± 0.83 versus control (CTRL) = 4.8 ± 2.01 (F = 61.86; p \u3c 0.0001). That properly functioning valve leaflets help maintain physiologic antegrade venous flow is indisputable. This study, however, suggests that the relative lack of valves may be related to the development of venous insufficiency. This report documents that patients with symptomatic reflux in the GSV have significantly fewer valves than patients with apparently normal functioning saphenous veins

    International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries

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    Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment
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