A beta-blocker did not improve outcomes in COPD patients without heart disease

Giving the beta-blocker metoprolol to people with chronic obstructive pulmonary disease who have no heart condition did not improve a combined measure of exacerbations, cardiovascular events and death, in a 1,695-patient randomised trial published in NEJM Evidence on September 6 [s1]. The drug missed its primary endpoint — but it also produced none of the excess hospitalisations that a widely cited earlier trial had flagged [s1][s3].

The practical upshot is a negative-but-reassuring result: no proven benefit from adding the drug, and no repeat of the safety signal that made clinicians wary.

Why the question keeps coming back

Observational studies have long suggested that beta-blockers — drugs that slow the heart and are standard after a heart attack or in heart failure — might also reduce exacerbations and deaths in COPD, even in patients without a cardiac reason to take them [s1]. The biological rationale is plausible, but randomised trials had been inconclusive [s1].

The most influential of those trials, BLOCK COPD, had actually raised an alarm. In 532 patients with moderate-to-severe COPD and no established indication for a beta-blocker, extended-release metoprolol did not lengthen the time to a first exacerbation (hazard ratio 1.05; 95% CI, 0.84 to 1.32; P=0.66), and the trial was stopped early for futility and safety [s3]. Crucially, metoprolol was associated with a higher risk of exacerbation leading to hospitalisation (hazard ratio 1.91; 95% CI, 1.29 to 2.83), and there were 11 deaths in the metoprolol group against 5 on placebo [s3]. That finding pushed many clinicians to avoid beta-blockers in COPD absent a cardiac indication.

What the new trial did

The new study was a multicentre, open-label, pragmatic, phase 4 randomised trial [s1]. Patients aged 40 or older with COPD, normal sinus rhythm and no cardiovascular disease were randomly assigned 1:1 to metoprolol at a target dose of 100 mg daily on top of standard care, or to standard care alone [s1]. The primary endpoint was the time to the first COPD exacerbation, cardiovascular event, or death over one year [s1].

A total of 1,695 patients were randomised; their mean age was 70 years and 62% were women [s1].

The results

The primary endpoint occurred in 27% of the metoprolol group and 30% of the standard-care group — a hazard ratio of 0.87 (95% CI, 0.73 to 1.05; P=0.14), which did not reach statistical significance [s1]. The component hazard ratios moved in the same modest direction without clearing significance: 0.88 (95% CI, 0.72 to 1.06) for COPD exacerbations, 0.73 (95% CI, 0.48 to 1.11) for cardiovascular events, 0.92 (95% CI, 0.48 to 1.77) for death, and 0.87 (95% CI, 0.58 to 1.28) for exacerbations requiring hospitalisation [s1].

Serious adverse events occurred in 80 of 848 participants (9.4%) on metoprolol and 66 of 847 (7.8%) on standard care; non-serious adverse events occurred in 293 (34.6%) and 247 (29.2%), respectively [s1].

How to read it

It is a negative trial on its primary endpoint. The confidence interval around the main hazard ratio crossed 1.0, and the P value was 0.14 [s1]. Nothing here establishes that metoprolol helps people with COPD and no heart disease.

But the safety picture differs from BLOCK COPD. Where the earlier trial found nearly a doubling of the risk of exacerbation requiring hospitalisation on metoprolol [s3], the new trial's hazard ratio for that same outcome was 0.87, pointing the other way, albeit not significantly [s1]. The two trials differed in design — open-label and pragmatic here, placebo-controlled there — and in population, so they are not a clean rematch.

Open-label design is a real limit. Patients and clinicians knew who was taking the drug, which can shape the reporting of exacerbations and the threshold to treat.

The result does not speak to patients who need a beta-blocker for their heart. This trial concerns people with no cardiovascular indication; for those with heart failure or after a heart attack, the case for beta-blockers rests on separate evidence.

An accompanying editorial by Wade and Dransfield — the latter an investigator on BLOCK COPD — weighs how to reconcile the two trials [s2]. The site has also covered beta-blocker discontinuation after a heart attack, where the question runs in the opposite direction: whether patients can safely stop.

What to watch

Whether a pooled or individual-participant analysis across the COPD beta-blocker trials resolves the conflicting safety signals, and whether any subgroup — defined by airflow limitation or exacerbation history — derives a benefit the overall average hides. The trial is registered as NCT03566667 [s1].

This article describes trial results, including a dose, for informational purposes only. It is not medical advice and not a recommendation about any medication.

Sources

• [s1] Sundh J, Magnuson A, Kvarnström M, et al. Metoprolol in Chronic Obstructive Pulmonary Disease without Cardiovascular Disease. NEJM Evidence, published online 2026-09-06.
• [s2] Wade RC, Dransfield MT. Beta-Blockers in COPD — Getting to the Heart of the Issue. NEJM Evidence, published online 2026-09-06.
• [s3] Dransfield MT, Voelker H, Bhatt SP, et al; BLOCK COPD Trial Group. Metoprolol for the Prevention of Acute Exacerbations of COPD. New England Journal of Medicine, 2019-10-20.