Efficacy and safety of dronedarone versus placebo in patients with atrial fibrillation stratified according to renal function: Post hoc analyses of the EURIDIS-ADONIS trials.

BACKGROUND: The use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Due to the propensity for CKD to occur alongside atrial fibrillation/atrial flutter (AF/AFL), it is essential that AAD safety and efficacy are assessed for patients with CKD. HYPOTHESIS: Dronedarone, an approved AAD, may present a suitable therapeutic option for patients with AF/AFL and concomitant CKD. METHODS: EURIDIS-ADONIS (EURIDIS, NCT00259428; ADONIS, NCT00259376) were identically designed, multicenter, double-blind, parallel-group trials investigating AF/AFL control with dronedarone 400 mg twice daily versus placebo (randomized 2:1). In this post hoc analysis, the primary endpoint was time to first AF/AFL. Patients were stratified according to renal function using the CKD-Epidemiology Collaboration equation and divided into estimated glomerular filtration rate (eGFR) subgroups of 30-44, 45-59, 60-89, and ≥90 ml/min. Time-to-events between treatment groups were compared using log-rank testing and Cox regression. RESULTS: At baseline, most (86%) patients demonstrated a mild or mild-to-moderate eGFR decrease. Median time to first AF/AFL recurrence was significantly longer with dronedarone versus placebo for all eGFR subgroups except the 30 to 44 ml/min group, where the trend was similar but statistical power may have been limited by the small population. eGFR stratification had no significant effect on serious adverse events, deaths, or treatment discontinuations. CONCLUSIONS: This analysis suggests that dronedarone could be an effective therapeutic option for AF with an acceptable safety profile in patients with impaired renal function.

Dronedarone vs. placebo in patients with atrial fibrillation or atrial flutter across a range of renal function: a post hoc analysis of the ATHENA trial.

AIMS: Use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is challenging owing to issues with renal clearance, drug accumulation, and increased proarrhythmic risks. Because CKD is a common comorbidity in patients with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish the efficacy and safety of AAD treatment in patients with CKD. METHODS AND RESULTS: Dronedarone efficacy and safety in individuals with AF/AFL and varying renal functionality [estimated glomerular filtration rate (eGFR): ≥60, ≥45 and <60, and <45 mL/min] was investigated in a post hoc analysis of ATHENA (NCT00174785), a randomized, double-blind trial of dronedarone vs. placebo in patients with paroxysmal or persistent AF/AFL plus additional cardiovascular (CV) risk factors. Log-rank testing and Cox regression were used to compare the incidence of endpoints between treatments. Overall, 4588 participants were enrolled from the trial. There was no interaction between treatment group and baseline eGFR assessed as a continuous variable (P = 0.743) for the first CV hospitalization or death from any cause (primary outcome). This outcome was lower with dronedarone vs. placebo across a wide range of renal function. First CV hospitalization and first AF/AFL recurrence were both lower in the two least renally impaired subgroups with dronedarone vs. placebo. Treatment emergent adverse events leading to treatment discontinuation were more frequent with dronedarone vs. placebo and occurred more often in patients with severe renal impairment. CONCLUSION: Dronedarone is an effective AAD in patients with AF/AFL and CV risk factors across a wide range of renal function.

Metabolic vs structural coma in the ED--an observational study.

BACKGROUND: Patients presenting unconscious may reasonably be categorized as suffering from a metabolic or structural condition. STUDY OBJECTIVE: The objective was to investigate if some routinely recorded clinical features may help to distinguish between these 2 main forms of coma in the emergency department (ED). METHODS: Adults admitted to an ED in Stockholm between February 2003 and May 2005 with a Glasgow Coma Scale (GCS) score less than 11 were enrolled prospectively. The GCS score was entered into a protocol that was complemented with available data within 1 month. RESULTS: The study population of 875 patients was classified into 2 main groups: one with a metabolic (n = 633; 72%) and one with a structural disorder (n = 242; 28%). Among the clinical features recorded in the ED, 3 were found to be strongly associated with a metabolic disorder, namely, young age, low or normal blood pressure, and absence of focal signs in the neurological examination. Patients younger than 51 years with a systolic blood pressure less than 151 mm Hg who did not display signs of focal pathology had a probability of 96% for having a metabolic coma. The mean GCS score on admission was identical in the groups. Hospital mortality was 14% in the metabolic and 56% in the structural group. CONCLUSIONS: These findings indicate that unconscious young adults who present without a traumatic incident with a low or normal blood pressure and without signs of focal pathology most probably suffer from a metabolic disorder, wherefore computed tomography of the brain may be postponed and often avoided.

Hospital mortality among poisoned patients presenting unconscious.

OBJECTIVES: The hospital mortality from acute poisoning in the western world is approximately 0.6%. However, this figure is based on series of consecutive cases, including mild intoxications. The aim of this paper was to investigate the mortality among poisoned patients with CNS depression on admission. DESIGN: This report is based on two case series. One observational study of 352 prospectively included cases of poisoning with a Glasgow coma scale (GCS) score ≤10 at presentation during the 2-year-period 2003-2005, and one retrospective review of all poisonings admitted to a hospital in Stockholm 2009-2011. RESULTS: The observational study showed a hospital mortality rate of 2.8%. Nine of the 10 fatalities had a GCS score below 7 on admission. The more recent retrospective review consisted of 1314 cases of poisoning of whom 419 (32%) had a GCS score ≤10 on admission. The hospital mortality among these 419 cases was 2.4%. All 10 deaths in this cohort had a GCS score below 7 at presentation. The subgroup of patients pooled from both case series with a GCS score of 3-6 (n =444) had a mortality rate of 4.3%. CONCLUSIONS: Based on the findings in this report, and on a literature search, about 30% of hospitalized poisonings have a significant CNS depression on admission. Based on our experience, cases of poisoning with a GCS score of 7-10 on admission do not seem to have a worse prognosis than poisonings in general. However, cases of poisoning presenting with deeper coma (GCS score 3-6) have a mortality rate approximately seven times higher than the overall hospital mortality from acute poisoning.

Prognosis in patients presenting with non-traumatic coma.

BACKGROUND: Studies of patients presenting with coma are limited, and little is known about the prognosis of these cases. OBJECTIVE: The aim of this study was to investigate the acute and long-term prognosis after an episode of non-traumatic coma. METHODS: Adults admitted consecutively to an emergency department in Stockholm, Sweden between February 2003 and May 2005 with a Glasgow Coma Scale (GCS) score of 10 or below were enrolled prospectively. All available data were used to explore the cause of the impaired consciousness on admission. Patients surviving hospitalization were followed-up for 2 years regarding survival. RESULTS: The final study population of 865 patients had the following eight different coma etiologies: poisoning (n = 329), stroke (n = 213), epilepsy (n = 113), circulatory failure (n = 60), infection (n = 56), metabolic disorder (n = 44), respiratory insufficiency (n = 33), and intracranial malignancy (n = 17). The hospital mortality rate among the 865 patients was 26.5%, varying from 0.9% for epilepsy to 71.7% for circulatory failure. The accumulated total 2-year mortality rate was 43.0%, varying from 13.7% for poisoning to 88.2% for malignancy. The level of consciousness on admission also influenced the prognosis: a GCS score of 3-6 was associated with a significantly higher hospital mortality rate than a GCS score of 7-10. CONCLUSION: The prognosis in patients presenting with non-traumatic coma is serious and depends largely on both the level of consciousness on admission and the etiology of the coma. Adding the suspected coma etiology to the routine coma grading of these emergencies may more accurately predict their prognosis.