ORIGINAL ARTICLE FREE PREVIEW

Metoprolol for the Prevention of Acute Exacerbations of COPD

Mark T. Dransfield, Helen Voelker, Surya P. Bhatt, et al

N Engl J Med 2019; 381:2304-2314
DOI: 10.1056/NEJMoa1908142

BACKGROUND 背景

Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.

观察性研究提示，beta受体阻滞剂能够减少中重度COPD患者病情加重及死亡的风险，但是这一发现并未经过随机试验验证。

METHODS 方法

In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.

在这项前瞻随机临床试验中，我们将年龄40-85岁的COPD患者进行随机分组，分别使用beta受体阻滞剂（缓释美托洛尔）或安慰剂。所有患者均有COPD病史，合并中度气流受限，根据既往病史或使用氧疗情况判断COPD急性加重风险较高。我们排除了已经使用或有明确指证使用beta受体阻滞剂的患者。主要预后终点为治疗期间（根据美托洛尔剂量调整，疗程为336至350天）首次COPD急性加重的时间。

RESULTS 结果

A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV₁) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P=0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.

共有532名患者接受随机分组。患者平均(±SD)年龄为 65.0±7.8 岁，平均FEV₁为预计值的 41.1±16.3%。由于主要预后终点无效及安全性考虑，试验提前终止。两组间首次发生COPD急性加重的中位时间无显著差异，美托洛尔组为 202 天，安慰剂组为 222 天 (风险比 美托洛尔 vs. 安慰剂, 1.05; 95% 可信区间 [CI], 0.84 to 1.32; P=0.66)。美托洛尔组因急性加重接受住院治疗的风险增加 (风险比, 1.91; 95% CI, 1.29 to 2.83)。可能与美托洛尔有关的副作用发生率两组相似，两组间非呼吸系统严重不良事件的总发生率也无差异。在治疗期间，美托洛尔组11例患者死亡，安慰剂组5例死亡。

CONCLUSIONS 结论

Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol.

对于没有明确beta受体阻滞剂指证的中重度COPD患者，美托洛尔组与安慰剂组患者发生首次COPD急性加重的事件相似。美托洛尔组患者因急性加重接受住院治疗更多。

(Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351. opens in new tab.)