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BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. METHODS: Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2-3). Assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism. The principal safety outcome was clinically relevant bleeding. Analyses were done by intention to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655. FINDINGS: The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD 5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; p<0.0001). There were 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists (1.1 vs 0.4 per 100 patient-years; p=0.014); elderly patients and those with renal impairment were at greater risk of such complications. There were 18 cases of thromboembolism with idraparinux and 27 cases with vitamin K antagonists (0.9 vs 1.3 per 100 patient-years; hazard ratio 0.71, 95% CI 0.39-1.30; p=0.007), satisfying the non-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists (3.2 vs 2.9 per 100 patient-years; p=0.49). INTERPRETATION: In patients with atrial fibrillation at ri

Background - The present study assessed the efficacy and safety of vernakalant hydrochloride ( RSD1235), a novel compound, for the conversion of atrial fibrillation ( AF). Methods and Results - Patients were randomized in a 2: 1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days ( short duration) and 8 to 45 days ( long duration). A first infusion of placebo or vernakalant ( 3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant ( 2 mg/kg) 15 minutes later if AF was not terminated. The primary end point was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n = 220; long duration, n = 116). Of the 145 vernakalant patients, 75 (51.7%) in the short-duration AF group converted to sinus rhythm ( median time, 11 minutes) compared with 3 of the 75 placebo patients ( 4.0%; P < 0.001). Overall, in the short-and long-duration AF groups, 83 of the 221 vernakalant patients (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients ( 2.6%; P < 0.001). Transient dysgeusia and sneezing were the most common side effects in vernakalant-treated patients. Four vernakalant-related serious adverse events (hypotension [ events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. Conclusion - Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated Udgivelsesdato: 2008/3/25

BACKGROUND: Although insulin secretion after carbohydrate ingestion is severely impaired in patients with type 2 diabetes, amino acid and protein co-ingestion can substantially increase plasma insulin responses. OBJECTIVE: We investigated insulin responses and the subsequent plasma glucose disposal rates after the ingestion of carbohydrate alone (CHO) or with a protein hydrolysate and amino acid mixture (CHO+PRO) in patients with a long-term diagnosis of type 2 diabetes. DESIGN: Ten type 2 diabetic patients [mean (+/-SEM) age: 62 +/- 2 y; body mass index (kg/m(2)): 27 +/- 1] and 9 healthy control subjects (age: 58 +/- 1 y; body mass index: 27 +/- 1) participated in 2 trials in which the plasma insulin response was measured after the ingestion of 0.7 g carbohydrate . kg(-1) . h(-1) with or without 0.35 g . kg(-1) . h(-1) of a mixture that contained a protein hydrolysate, leucine, and phenylalanine. Continuous infusions with [6,6-(2)H(2)]glucose were then given to investigate plasma glucose disposal. RESULTS: Plasma insulin responses were higher by 299 +/- 64% and 132 +/- 63% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The subsequent plasma glucose responses were reduced by 28 +/- 6% and 33 +/- 3% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P < 0.001). The reduced plasma glucose response in the diabetic patients was attributed to a 13 +/- 3% increase in glucose disposal (P < 0.01). CONCLUSIONS: The combined ingestion of carbohydrate with a protein hydrolysate and amino acid mixture significantly increases de novo insulin production in patients with a long-term diagnosis of type 2 diabetes. The increased insulin response stimulates plasma glucose disposal and reduces postprandial glucose concentrations.