Comparison of extrafine beclomethasone dipropionate/formoterol fumarate dry powder inhaler and pressurized metered-dose inhaler in Chinese patients with asthma: the FORTUNE study.

OBJECTIVE: When selecting inhaled therapies, it is important to consider both the active molecules and the device. Extrafine formulation beclomethasone dipropionate plus formoterol fumarate (BDP/FF) has been available for some years delivered via pressurized metered-dose inhaler (pMDI). More recently, a breath-activated, multi-dose dry-powder inhaler (DPI), the NEXThaler, has been approved. The current study aimed to demonstrate the non-inferiority of BDP/FF delivered via the DPI vs. via the pMDI, in Chinese adults with asthma. METHODS: After a four-week run-in period, when all patients received BDP/FF pMDI 100/6 µg, two inhalations twice daily (BID), patients were randomized equally to BDP/FF pMDI or DPI, both 100/6 µg, two inhalations BID for 12 weeks. The primary objective was to demonstrate non-inferiority of BDP/FF DPI vs. BDP/FF pMDI in terms of average pre-dose morning peak expiratory flow (PEF) over the entire treatment period. RESULTS: Of 252 and 242 patients in the DPI and pMDI groups, respectively, 88.5% and 88.8% completed the study. The primary objective was met, with no statistically significant difference between the treatments in average pre-dose morning PEF, and with the lower limit of the 95% CI above the -15 L/min non-inferiority margin (adjusted mean difference: 5.25 L/min [95% CI: -0.56, 11.06]). Adverse events were reported by 48.4% and 49.6% patients in the DPI and pMDI groups, respectively, most mild or moderate. CONCLUSIONS: The NEXThaler DPI is a similarly effective device to the pMDI for the administration of BDP/FF in adults, so extending the options available for the management of asthma.

Most appropriate animal models to study the efficacy of statins: a systematic review.

BACKGROUND: In animal models and clinical trials, statins are reported as effective in reducing cholesterol levels and lowering the risk of cardiovascular diseases. We have aggregated the findings in animal models - mice, rats and rabbits - using the technique of systematic review and meta-analysis to highlight differences in the efficacy of statins. MATERIALS AND METHODS: We searched Medline and Embase. After examining all eligible articles, we extracted results about total cholesterol and other blood parameters, blood pressure, myocardial infarction and survival. Weighted and standard mean difference random effects meta-analysis was used to measure overall efficacy in prespecified species, strains and subgroups. RESULTS: We included in systematic review 161 animal studies and we analysed 120 studies, accounting for 2432 animals. Statins lowered the total cholesterol across all species, although with large differences in the effect size: -30% in rabbits, -20% in mice and -10% in rats. The reduction was larger in animals fed on a high-cholesterol diet. Statins reduced infarct volume but did not consistently reduce the blood pressure or effect the overall survival. Few studies considered strains at high risk of cardiovascular diseases or hard outcomes. CONCLUSIONS: Although statins showed substantial efficacy in animal models, few preclinical data considered conditions mimicking human pathologies for which the drugs are clinically indicated and utilized. The empirical finding that statins are more effective in lowering cholesterol derived from an external source (i.e. diet) conflicts with statin's supposed primary mechanism of action.

Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: data from the GISSI-AF trial.

BACKGROUND: Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. METHODS: We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences - where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. RESULTS: Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). CONCLUSIONS: TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF. TRIAL REGISTRATION NUMBER: NCT00376272.