Bisoprolol Did Not Improve Cardiorespiratory Outcomes in COPD Trial

A recent study reports no overall cardiorespiratory advantage for bisoprolol over placebo in the PACE phase 3 trial among adults with moderately severe COPD. This double-blind, randomized, controlled phase 3 trial ran across 22 hospital and research institute sites in Australia, India, New Zealand, and Sri Lanka. Eligible participants were 40 to 85 years old, had post-bronchodilator FEV1 values of 30% to 70% predicted, and had at least one exacerbation within two years. The trial evaluated bisoprolol added to usual COPD care in this clinically defined group.

Investigators randomly assigned 280 participants to bisoprolol 1.25 to 5 mg or matched placebo, taken orally once daily, with follow-up for two years. Usual COPD therapy continued in both groups, setting the beta blocker against placebo on top of standard respiratory management. Allocation used a concealed, computer-generated sequence stratified by site, smoking status, and previous cardiovascular disease that required treatment. Participants, site personnel, and investigators remained masked to treatment assignment throughout the study period.

For the prespecified hierarchical cardiorespiratory outcome, investigators assessed death first, then hospital admissions, exacerbations, quality of life measures, and FEV1. Researchers observed 3041 hierarchical comparisons favoring bisoprolol, 3240 favoring placebo, and 482 ties, which yielded a win ratio of 0.95. The 95% CI for the win ratio was 0.72 to 1.25, with p=0.72, and the net benefit was -2%, 95% CI -15 to 10. In the primary analysis, the prespecified hierarchy did not distinguish the two groups.

Authors reported no significant between-group differences in all-cause mortality, cardiorespiratory hospitalizations, major adverse cardiac events, or moderate or severe COPD exacerbations. They also reported no significant differences in FEV1, COPD symptoms, or quality of life over follow-up.

Within the studied once-daily 1.25 to 5 mg regimen, overall adverse events did not differ significantly between groups. COPD exacerbations were the most common adverse event, reported in 83 participants, or 58%, with bisoprolol and 87 participants, or 64%, with placebo. No deaths in either group were attributed to treatment. The authors concluded that bisoprolol made no difference to overall cardiorespiratory health, all-cause mortality, or serious cardiorespiratory events in moderately severe COPD, consistent with the broadly neutral pattern across reported outcomes.

Key Takeaways

• The phase 3 trial compared once-daily bisoprolol added to usual COPD care with matched placebo in adults with moderately severe COPD and prior exacerbations.
• The prespecified hierarchical cardiorespiratory outcome did not distinguish bisoprolol from placebo.
• Researchers reported no significant between-group differences in all-cause mortality, cardiorespiratory hospitalizations, major adverse cardiac events, moderate or severe COPD exacerbations, FEV1, COPD symptoms, or quality of life, and no deaths in either group were attributed to treatment.