摘要
Background Endothelin-receptor blockade provides haemodynamic benefit in expe rimental and clinical heart failure. We aimed to measure the effects of long-te rm endothelin-blockade on left-ventricular (LV) remodelling and clinical outco mes in patients with chronic heart failure. Methods 642 patients with chronic he art failure were assigned the oral endothelinA-antagonist darusentan at 10, 25, 50, 100, or 300 mg daily or placebo for 24 weeks in addition to standard therap y in a randomised, doubleblind, placebo-controlled trial. In the 50-300 mg gro ups, darusentan was uptitrated over 6 weeks. Primary endpoint was change in LV e nd-systolic volume (LVESV) at 24 weeks from baseline, measured by MRI. All pati ents for whom assessable MRI scans were available at baseline and follow-up wer e included in the analysis. Findings Darusentan was well tolerated. LVESV could be assessed in 485 (76%) patients with paired MRI data at baseline and 6 months . The change in LVESV was not significantly different from that with placebo at any dose (mean difference from placebo 1.27 mL <<95%CI -9.9 to 12. 4>> with 10 m g dose, -1.84 mL <<-13.0 to 9.3>> with 25 mg, -5.68 mL <<-16.9 to 5.6>> with 50 mg, -4.05 mL <<-15.5 to 7. 4>> with 100 mg, and -4.34 mL <<-15.7 to 7. 0>> with 300 mg). Heart failure worsened in 71 (11.1%) patients, and 30 (4.7%) died dur ing the study with no difference between groups. Interpretation EndothelinA bloc kade with darusentan did not improve cardiac remodelling or clinical symptoms or outcomes in patients with chronic heart failure receiving an angiotensin-conve rting-enzyme inhibitor, βblocker, or aldosterone antagonist. Thus, endothelinA blockade is unlikely to be useful as an add-on treatment in such patients.
Background Endothelin-receptor blockade provides haemodynamic benefit in expe rimental and clinical heart failure. We aimed to measure the effects of long-te rm endothelin-blockade on left-ventricular (LV) remodelling and clinical outco mes in patients with chronic heart failure. Methods 642 patients with chronic he art failure were assigned the oral endothelinA-antagonist darusentan at 10, 25, 50, 100, or 300 mg daily or placebo for 24 weeks in addition to standard therap y in a randomised, doubleblind, placebo-controlled trial. In the 50-300 mg gro ups, darusentan was uptitrated over 6 weeks. Primary endpoint was change in LV e nd-systolic volume (LVESV) at 24 weeks from baseline, measured by MRI. All pati ents for whom assessable MRI scans were available at baseline and follow-up wer e included in the analysis. Findings Darusentan was well tolerated. LVESV could be assessed in 485 (76%) patients with paired MRI data at baseline and 6 months . The change in LVESV was not significantly different from that with placebo at any dose (mean difference from placebo 1.27 mL <<95%CI -9.9 to 12. 4>> with 10 m g dose, -1.84 mL <<-13.0 to 9.3>> with 25 mg, -5.68 mL <<-16.9 to 5.6>> with 50 mg, -4.05 mL <<-15.5 to 7. 4>> with 100 mg, and -4.34 mL <<-15.7 to 7. 0>> with 300 mg). Heart failure worsened in 71 (11.1%) patients, and 30 (4.7%) died dur ing the study with no difference between groups. Interpretation EndothelinA bloc kade with darusentan did not improve cardiac remodelling or clinical symptoms or outcomes in patients with chronic heart failure receiving an angiotensin-conve rting-enzyme inhibitor, βblocker, or aldosterone antagonist. Thus, endothelinA blockade is unlikely to be useful as an add-on treatment in such patients.
