Why is LABA-LAMA preferred over LABA-ICS for preventing COPD exacerbations?
Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD (FLAME)
Wedzicha JA et al. NEJM (June 2016)
Bottom Line: This 52-week, randomized, double-blind, double-dummy, noninferiority trial evaluated the effectiveness of a LABA-LAMA once daily (indacaterol 110 μg plus glycopyrronium 50 μg) versus LABA-ICS twice daily (salmeterol 50 μg plus fluticasone 500 μg) in 3362 patients with COPD who had at least one exacerbation in the last year. The primary outcome was the annual rate of COPD exacerbations. Indacaterol–glycopyrronium showed not only noninferiority but also superiority to salmeterol–fluticasone in reducing the annual rate of all COPD exacerbations. The rate of exacerbations was 11% lower in the indacaterol–glycopyrronium group than in the salmeterol–fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003), independent of baseline blood eosinophil count. In addition, the LABA-LAMA group had a longer time to first exacerbation compared to the LABA-ICS group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). Safety outcomes indicated a pneumonia incidence of 3.2% in the intervention group versus 4.8% in the comparator group (P=0.02). The study concluded that maintenance indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations.
Why should I consider EVT beyond 6 hours in my patient with stroke?
Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct (DAWN)
Nogueria RG et al. NEJM (November 2017)
Bottom Line: This randomized clinical trial evaluated the effect of endovascular thrombectomy plus standard care versus standard care alone in patients with acute ischemic stroke due to occlusion of the intracranial internal carotid artery or proximal middle cerebral artery. A total of 206 patients were enrolled, all of whom were last seen well 6-24 hours earlier and who had a mismatch between severity of clinical deficit and infarct volume. Primary outcomes included mean disability score on the utility-weighted modified Rankin scale (5.5 in the thrombectomy group vs. 3.4 in the control group; adjusted difference [Bayesian analysis], 2.0 points; 95% CI, 1.1 to 3.0; posterior probability of superiority, >0.999) and functional independence at 90 days (49% vs. 13%; adjusted difference, 33%; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). Safety outcomes showed similar rates of symptomatic intracranial hemorrhage and mortality. The study concluded that thrombectomy plus standard care significantly improved disability outcomes compared to standard care alone in this patient population.
What’s the evidence for remdesivir as a treatment for patients hospitalized with COVID-19?
Remdesivir for the Treatment of Covid-19 — Final Report (ACTT-1)
Beigel JH et al. NEJM (May 2020)
Bottom Line: This double-blind, randomized, placebo-controlled trial evaluated intravenous remdesivir in adults hospitalized with Covid-19 and lower respiratory tract infection. A total of 1062 patients were randomized, receiving either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily) or placebo for up to 10 days. The primary outcome was time to recovery, defined by either hospital discharge or hospitalization for infection-control purposes only. The remdesivir group showed a median of 10 days to recovery (95% CI, 9 to 11) versus 15 days for placebo (95% CI, 13 to 18), with a rate ratio of 1.29 (95% CI, 1.12 to 1.49; P<0.001). Serious adverse events occurred in 24.6% of the remdesivir group compared to 31.6% in the placebo group. The study concluded that remdesivir significantly shortens recovery time in this patient population.
Trial Files Issue #2025-10