Metoprolol for the Prevention of Acute Exacerbations of COPD
Metoprolol for the Prevention of Acute Exacerbations of COPD
复制标题
DOI：
10.1056/nejmoa1908142
复制
发表时间：
2019-12-12
影响因子：
158.5
通讯作者：
Connett, J. E.
中科院分区：
文献类型：
--
作者：
Dransfield, M. T.;Voelker, H.;Connett, J. E.
背景观察性研究表明，β 受体阻滞剂可能会降低中度或重度慢性阻塞性肺疾病 (COPD) 患者病情加重和死亡的风险，但这些发现尚未在随机试验中得到证实。 方法在这项前瞻性随机试验中，我们将年龄在 40 至 85 岁之间的 COPD 患者分配到接受 β 受体阻滞剂（缓释美托洛尔）或安慰剂治疗。所有患者都有慢性阻塞性肺病（COPD）临床病史，伴有中度气流受限和病情加重风险增加，前一年的病情加重史或规定使用补充氧气即可证明这一点。我们排除了已经服用β受体阻滞剂或已确定使用此类药物的患者。主要终点是治疗期间直至 COPD 首次恶化的时间，范围为 336 至 350 天，具体取决于美托洛尔的调整剂量。 结果 共有 532 名患者接受了随机分组。患者的平均年龄 (+/- SD) 为 65.0 +/- 7.8 岁； 1 秒平均用力呼气量 (FEV 1) 为预测值的 41.1 +/- 16.3%。由于主要终点无效和安全性问题，该试验提前停止。直到第一次恶化的中位时间没有显着的组间差异，美托洛尔组为 202 天，安慰剂组为 222 天（美托洛尔与安慰剂的风险比为 1.05；95% 置信区间 [CI]，0.84 至 1.32；P = 0.66）。美托洛尔与导致住院的病情加重风险较高相关（风险比，1.91；95% CI，1.29至2.83）。两组中可能与美托洛尔相关的副作用发生率相似，非呼吸系统严重不良事件的总体发生率也相似。治疗期间，美托洛尔组有 11 例死亡，安慰剂组有 5 例死亡。结论：在没有确定使用 β 受体阻滞剂指征的中度或重度 COPD 患者中，美托洛尔组和安慰剂组到第一次 COPD 恶化的时间相似。在接受美托洛尔治疗的患者中，因病情加重而住院的情况更为常见。
BACKGROUNDObservational 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.METHODSIn 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.RESULTSA 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 (FEV 1) 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.CONCLUSIONSAmong 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.