In patients who were randomized to the lebrikizumab treatment, there was a statistically significant improvement in FEV1 of 5.5%, which occurred almost immediately and was sustained for the entire 32 weeks of the study. The improvement was more significant in patients who had high surrogate markers for IL-13. Despite this improvement in FEV1, there were no differences in secondary outcomes except in patients who had surrogate markers for high IL-13 levels.
Bottom line: In adults with asthma who remained uncontrolled despite inhaled corticosteroid therapy, IL-13 antagonism with lebrikizumab improved FEV1. However, the clinical relevance of these modest improvements remains unclear.
Citation: Corren J, Lemanske R, Matthews J, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088-1098.
Rivaroxaban Is Noninferior to Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does rivaroxaban compare with warfarin in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation?
Background: Warfarin is effective for the prevention of stroke in atrial fibrillation, but it requires close monitoring and adjustment. Rivaroxaban, an oral Xa inhibitor, may be safer, easier, and more effective than warfarin.
Study design: Multicenter, randomized, double-blind, double-dummy trial.
Setting: 1,178 sites in 45 countries.
Synopsis: The study included 14,264 patients with nonvalvular atrial fibrillation who were randomized to either fixed-dose rivaroxaban (20 mg daily or 15 mg daily for CrCl 30-49 mL/min) plus placebo or adjusted-dose warfarin (target INR 2.0 to 3.0) plus placebo. The mean CHADS2 score was 3.5. The primary endpoint (stroke or systemic embolism) occurred in 1.7% of patients per year in the rivaroxaban group and 2.2% per year in the warfarin group (hazard ratio for rivaroxaban 0.79; 95% CI: 0.66 to 0.96, P<0.001 for noninferiority). There was no difference in major or nonmajor clinically significant bleeding between the two groups (14.9% rivaroxaban vs. 14.5% warfarin, hazard ratio=1.03, 95% CI: 0.96 to 1.11, P=0.44). There were fewer intracranial hemorrhages (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.
Bottom line: In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolization, with a similar risk of major bleeding and a lower risk of intracranial hemorrhage or fatal bleeding.
Citation: Patel MR, Mahaffey K, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-891.
Apixaban More Effective and Safer than Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does the effectiveness and safety of apixaban compare with warfarin for stroke prevention in atrial fibrillation?
Background: Until recently, warfarin has been the only available oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF). The oral factor Xa inhibitors have shown similar efficacy and safety, without the monitoring requirement and drug interactions associated with warfarin.
Study design: Prospective randomized double-blind controlled trial.
Setting: More than 1,000 clinical sites in 39 countries.
Synopsis: This study randomized 18,201 patients with atrial fibrillation or flutter and at least one CHADS2 risk factor for stroke to receive oral apixaban or warfarin therapy. Exclusion criteria were prosthetic valves and severe kidney disease. The median duration of follow-up was 1.8 years, and the major endpoints were incidence of stroke, systemic embolism, bleeding complications, and mortality.
Compared with warfarin, apixaban reduced the annual incidence of stroke and systemic embolism from 1.6% to 1.3% (HR 0.79, 95%: CI 0.66 to 0.95, P=0.01 for superiority), and reduced mortality (HR: 0.89, 95% CI: 0.80 to 0.998). For the combined endpoint of stroke, systemic embolism, MI, or death, the annual rate was reduced from 5.5% to 4.9% (HR: 0.88, 95% CI: 0.80 to 0.97). All measures of bleeding were less frequent with apixaban: major 2.1% vs. 3.1% (HR: 0.69, 95% CI: 0.60 to 0.80), and combined major and minor bleeding 4.1% vs. 6.0% (HR: 0.68, 95% CI: 0.61 to 0.75). The annual rate for the net outcome of stroke, embolism, or major bleeding was 3.2% with apixaban and 4.1% with warfarin (HR: 0.77, 95% CI: 0.69 to 0.86).