Efficacy and safety of vernakalant in recent-onset atrial fibrillation after the European medicines agency approval: systematic review and meta-analysis.

Vernakalant is an emergent antiarrhythmic drug that, in preclinical studies, has demonstrated high efficacy in restoring sinus rhythm and safety in patients with rapid recent-onset atrial fibrillation. The aim of this work was to evaluate the efficacy and safety of vernakalant for cardioversion of recent-onset atrial fibrillation. PubMed, EMBASE, Clinical Trials Registry, and European Medicines Agency public reports were searched for randomized clinical trials, until May 2011, of vernakalant compared with controls (placebo/other antiarrhythmic drug) in enrolled patients with high ventricular rate atrial fibrillation. Five randomized trials that met inclusion criteria enrolled a total of 1099 patients. Among these, 810 had recent-onset atrial fibrillation. When compared with controls (placebo/other oral antiarrhythmic drugs), vernakalant was associated with a significant increase in cardioversion within 90 minutes from drug infusion (relative risk, 8.4; 95% confidence interval, 4.4-16.3; P < .00001). Compared with controls, vernakalant was not associated with a significant difference in serious adverse events (relative risk, 0.9; 95% confidence interval, 0.6-1.4; P = .64). The authors conclude that compared with controls, vernakalant is effective and safe for rapidly converting recent-onset atrial fibrillation. Questions remain surrounding safety because 1 unpublished trial was discontinued for this reason. Further cost-effective analysis and comparison with other antiarrhythmic agents, such as class I antiarrhythmic agents, should be investigated, especially in the emergency department.

Glomerular filtration rate and serum phosphate: an inverse relationship diluted by age.

BACKGROUND: Available data indicate that serum phosphate increases only when glomerular filtration rate (GFR) falls into the low range (<60 mL/min x 1.73 m(2)). GFR and serum phosphate decrease with ageing. This population-based study investigated by age-controlled analyses the relationship of GFR with serum phosphate in adults with GFR above the low range. METHODS: Data were collected on age, sex, menstrual status, anthropometry, overnight urinary creatinine, dietary protein (overnight urinary urea), reported intake of milk/yogurt, serum creatinine, phosphate, calcium and total protein in 4034 adults (age 18-91 years) with GFR >or=60 mL/min x 1.73 m(2) as assessed by estimated GFR (eGFR, simplified MDRD equation) and creatinine clearance (overnight urinary creatinine/serum creatinine). RESULTS: The relationship of eGFR with serum phosphate was positive in men and null in women in univariate analyses (P = 0.001 and 0.148), negative in both sexes with age adjustment (P < 0.001). Age-adjusted results did not depend on colinearity between age and eGFR because the relationship was inverse also replacing eGFR with creatinine clearance (P < 0.001 in both sexes). In univariate regression analysis done separately by gender and six age-strata (18-24, 25-34, 35-44, 45-54, 55-64 and >or=65), the line of serum phosphate over eGFR was constantly inverse (range of P = 0.010/0.089) with the progressively lower y-axis intercept from young to older ages. The inverse relationship of eGFR or creatinine clearance with serum phosphate was significantly inverse also controlling for other variables (P < 0.01). CONCLUSIONS: GFR differences in the range >or=60 mL/min x 1.73 m(2) are inversely and independently related to serum phosphate. The relationship is undetectable without age-controlled procedures because, for serum phosphate, the effect of GFR differences above >or=60 mL/min x 1.73 m(2) is much smaller than the effect of age.

Twenty-year cardiovascular and all-cause mortality trends and changes in cardiovascular risk factors in Gubbio, Italy: the role of blood pressure changes.

AIMS: In an observational population study that lasted 20 years, the relationships between mortality trends and changes in cardiovascular risk factor levels were examined. METHODS AND RESULTS: In the town of Gubbio, in central Italy, population surveys for measurement of cardiovascular risk factors were performed 20 years apart. In a subset of the initial cohort (1927 men and 2333 women), mortality data were collected for 20 years. Cardiovascular risk factor levels were compared in individuals in the same age range (20-79 years) examined at the initial survey (1927 men and 2333 women) and at the final survey (1761 men and 2055 women). Age-adjusted rates significantly declined, by 28% among men and 51% among women, for all causes of death, and by 50% among men and 71% among women for cardiovascular disease deaths. Declines were observed in the levels of systolic blood pressure, serum cholesterol, resting heart rate, smoking habits, BMI, plasma glucose (the latter two only in women) and the estimated cardiovascular risk, together with increases in serum high-density lipoprotein cholesterol and in the proportion of treated and controlled hypertensive patients. CONCLUSION: Although similar but less impressive changes were recorded in Italy at large, the existence of the observational study in Gubbio might have motivated the general population and the medical profession towards actions promoting general health.