metoprolol and copd
Effect on mortality of metoprolol in acute myocardial infarction: a double-blind randomised trial. Beta-blockers are safe for most patients with asthma and COPD? This study should not change practice. 15. § COPD exacerbations that are listed here may not meet the protocol-defined criteria for the primary end point. would have regressed towards the mean, had the study been completed). In the BLOCK COPD (Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) trial, we investigated the effect of the beta-blocker metoprolol, as compared with placebo, on the risk of COPD exacerbations among patients who were at high risk for such events.22 We hypothesized that the use of metoprolol would lower the risk of exacerbations in these patients without having an adverse effect on lung function, results on a 6-minute walk test, dyspnea, or quality of life. A complete list of nonfatal serious adverse events is provided in Table S2. No other potential conflict of interest relevant to this article was reported. J Am Coll Cardiol 2006;47:2554-2560. Evaluation of clinical methods for rating dyspnea. Suissa S, Ernst P. Beta-blockers in COPD: a methodological review of the observational studies. This isolated secondary endpoint is of dubious significance for several reasons – it’s statistically weak, the study was stopped prematurely, baseline imbalances exist between the groups, and there isn’t a coherent signal of harm across multiple secondary endpoints. BMJ Open 2016;6(6):e012292-e012292. S1A). PulmCrit – Six RCTs to answer one question: what is the role of tocilizumab in COVID-19? JAMA 2000;283:1295-1302. Transl Res 2013;162:237-251. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days (95% confidence interval [CI], 162 to 282) in the metoprolol group and 222 days (95% CI, 189 to 295) in the placebo group (Figure 2A). Risk indexes for exacerbations and hospitalizations due to COPD. might be causing an increased mortality. Patients in the metoprolol group had a lower mean heart rate than those in the placebo group (difference, 6 to 10 beats per minute) (Fig. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group. In addition, more discontinuations occurred in the metoprolol group than in the placebo group, which suggests the presence of adverse respiratory effects not captured by spirometry. Chest 2007;132:456-463. Beta-blocker use and COPD mortality: a systematic review and meta-analysis. Am J Respir Crit Care Med 2017;195:557-582. Effect of β blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records. Post was not sent - check your email addresses! We based the sample size and considerations for statistical power on the primary end point of the time until the first exacerbation of COPD. ‡ Scores on the COPD Assessment Test range from 0 to 40, with lower scores indicating better functioning and with a minimal clinically important difference of 2 points. In-hospital and 5-year mortality of patients treated in the ICU for acute exacerbation of COPD: a retrospective study. 26. NEW! 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Metoprolol was well tolerated for 3 months by 50 patients with coexistent CAD and mild to severe COPD. ), Minneapolis, HealthPartners Minnesota, Bloomington (C.M. 35. Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. 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. Kon SS, Canavan JL, Jones SE, et al. 22. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. Stat Med 1994;13:1341-1356. * Plus–minus values are means ±SD. The 36. van der Woude HJ, Zaagsma J, Postma DS, Winter TH, van Hulst M, Aalbers R. Detrimental effects of beta-blockers in COPD: a concern for nonselective beta-blockers. vast majority of these secondary endpoints were negative. Fourth, we do not know whether these results would be similar for other cardioselective beta-blockers or for noncardioselective agents, although concern regarding adverse respiratory effects is greater with the latter.36 Finally, we did not enroll patients who had a proven indication for the use of a beta-blocker or who were already taking the drugs, so our results do not inform the risk of COPD exacerbations with metoprolol in such patients. We used Student’s t-tests to compare annualized rates of hospitalization and nonfatal serious adverse events and used mixed-effects models with patient-specific random intercepts to compare between-group differences in changes in continuous measures of secondary end points. Although observational studies have suggested that the benefits of beta-blockers in patients with recent myocardial infarction and heart failure extend to those with COPD,15,19 this hypothesis has not been prospectively confirmed, and randomized trials to determine the overall risk–benefit ratio in such patients may be needed. Dr. Dransfield reports receiving consulting fees and serving on clinical trials for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and PneumRx/BTG, serving on clinical trials for Novartis, Yungjin, Boston Scientific, Gala Therapeutics, and Nuvaira, receiving travel support and serving on clinical trials for Pulmonx, and receiving consulting fees from Quark Pharmaceuticals and Mereo; Dr. Bhatt, receiving advisory board fees from Sunovion and GlaxoSmithKline and research funding, paid to his institution, from ProterixBio; Dr. Casaburi, receiving grant support, advisory board fees, and lecture fees from GlaxoSmithKline, Boehringer Ingelheim, and AstraZeneca, consulting fees from Regeneron and Genentech, and owning stock in Inogen; Dr. Come, receiving clinical trial support from Sunovion Pharmaceuticals; Dr. Criner, receiving grant support and consulting fees from Boehringer Ingelheim, grant support from Novartis, AstraZeneca, Respironics, MedImmune, Actelion, Forest, Pearl, Ikaria, Aeris, PneumRx, and Pulmonx, having an equity interest in Healthcare Solutions, receiving consulting fees from Amirall and Holaira, and receiving grant support and serving as a consultant for GlaxoSmithKline; Dr. Han, receiving consulting fees and honoraria from GlaxoSmithKline, AstraZeneca, and Boehringer Ingelheim, consulting fees from Mylan, and research support from Sunovion and Novartis; Dr. Jain, receiving consulting fees, advisory fees, and lecture fees from AstraZeneca Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Genentech, Mallinckrodt, and GlaxoSmithKline; Dr. Kalhan, receiving grant support, consulting fees, and lecture fees from Boehringer Ingelheim and GlaxoSmithKline, grant support from PneumRx/BTG and Spiration, grant support and consulting fees from AstraZeneca, and consulting fees from CVS Caremark, Aptus Health, Boston Scientific, and Boston Consulting Group; Dr. Kaminsky, receiving lecture fees from MGC Diagnostics; Dr. Kaner, receiving grant support, consulting fees, and lecture fees from Genentech and Boehringer Ingelheim, fees for serving on an adjudication committee from MedImmune and Gilead, and grant support from Bristol-Myers Squibb, Afferent, Respivant, and Toray; Dr. Kunisaki, receiving consulting fees from GlaxoSmithKline and Nuvaira; Dr. Make, receiving grant support, paid to National Jewish Health, fees for serving as an international principal investigator on a clinical trial, advisory board fees, and presentation fees from AstraZeneca, serving as a reviewer and serving on a data and safety monitoring board for Spiration, grant support, paid to National Jewish Health, advisory board fees, and presentation fees from GlaxoSmithKline, grant support, paid to National Jewish Health, and medical board fees from Sunovion, participating in CME activities for WebMD, Up-To-Date, Projects in Knowledge, Hybrid Communications, Medscape, and Catamount Medical, serving as a consultant and on an advisory board for Novartis, receiving grant support, paid to National Jewish Health, from Pearl Therapeutics, advisory board fees from Verona, Boehringer Ingelheim, Theravance, Circassia, Phillips, and Science 24/7, consulting fees from Third Pole, and fees for serving on a data safety and monitoring board from Shire; Dr. Martinez, receiving advisory board fees, fees for serving on a steering committee, presentation fees, and travel support from AstraZeneca, advisory board fees, presentation fees, fees for serving on a data and safety monitoring board, and travel support from Boehringer Ingelheim, advisory board fees and trial support from ProterixBio, advisory board fees, fees for serving on a data and safety monitoring board, and travel support from Genentech, advisory board fees, fees for serving on a steering committee, fees for serving on a data and safety monitoring board, presentation fees, and travel support from GlaxoSmithKline, honoraria and travel support from MD Magazine, honoraria and travel support from Miller Communications, advisory board fees, presentation fees, and travel support from Novartis, advisory board fees, fees for serving on a steering committee, and travel support from Pearl Therapeutics, honoraria and travel support from PeerView Communications, honoraria and travel support from Prime Communications, honoraria, advisory board fees, and travel support from Chiesi, advisory board fees and travel support from Sunovion, advisory board fees and travel support from Theravance, honoraria from UpToDate, honoraria from WebMD/MedScape, fees for serving on a steering committee from Afferent/Merck, fees for serving on a steering committee from Gilead, fees for serving on a steering committee and travel support from Nitto, honoraria and serving on a steering committee for Patara/Respivant, honoraria and travel support from Potomac Center for Medical Education, serving on a data and safety monitoring board and serving on a steering committee for Biogen, fees for serving on a steering committee from Veracyte, advisory board fees and travel support from Zambon, honoraria and travel support from Physicians Education Resource, honoraria from Rockpointe, serving on a steering committee for Prometic, honoraria from Rare Disease Healthcare Communications, serving on a steering committee for Bayer, serving as an advisor for Bridge Biotherapeutics, honoraria and travel support from Canadian Respiratory Network, serving on a steering committee for Promedior, advisory board fees and travel support from Teva, and serving on an advisory board for Gala Therapeutics; Dr. McEvoy, receiving grant support from GlaxoSmithKline and consulting fees from Respirtech; Dr. Reed, receiving grant support from Janssen Research and Development; Dr. Scanlon, receiving grant support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi; Dr. Sciurba, receiving grant support from Astellas, AstraZeneca, PneumRx/BTG, Pulmonx, Nuvaira, and Gala Therapeutics and advisory board fees from GlaxoSmithKline, Verona, and Theravance; Dr. Sriram, receiving grant support from AstraZeneca and GlaxoSmithKline; Dr. Stringer, receiving grant support from AstraZeneca and Boehringer Ingelheim, consulting fees and fees for serving on a data and safety monitoring board from Allergan, and fees for serving on a data and safety monitoring board from Syneos Health; Dr. Wells, receiving grant support from Bayer, grant support and advisory board fees from GlaxoSmithKline and Mereo BioPharma, advisory board fees from Boehringer Ingelheim, and serving as end-point adjudicator for Quintiles and PRA Health Sciences; and Dr. Lazarus, receiving fees for education from Boehringer Ingelheim. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Second, our trial population had moderate or severe COPD with a high prevalence of supplemental oxygen use and previous hospitalization for COPD. 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. From the Lung Health Center, University of Alabama at Birmingham (M.T.D., S.P.B., J.M.W., E.W. and the Minneapolis VA Medical Center (K.M.K. This Fihn SD, Gardin JM, Abrams J, et al. Bhatt SP, Dransfield MT. In a murine model of antigen-induced airway inflammation and AHR, duration of therapy was the determinant of response to β-AR ligands . † For nonfatal adverse events, P values were calculated by Student’s t-test. Government Leaders and Prioritization of SARS-CoV-2 Vaccines, Vaccinating Children against Covid-19 — The Lessons of Measles, Beyond Tuskegee — Vaccine Distrust and Everyday Racism, Covid-19 Vaccine Injuries — Preventing Inequities in Compensation, Addressing Child Hunger When School Is Closed — Considerations during the Pandemic and Beyond. All the analyses are based on the intention-to-treat principle. The risk of exacerbations of COPD was similar in the metoprolol group and the placebo group among patients with moderate or severe COPD who were at increased risk for exacerbations and had no proven indication for beta-blockers. S1B). 4. 18. This led to the current BLOCK-COPD trial which (spoiler alert) shows that metoprolol isn’t beneficial for COPD. The starting dose was one 50-mg tablet of metoprolol or matching placebo taken orally daily. Number of hospital admissions for COPD over a year, Number of hospital days due to COPD exacerbations over a year, Major adverse coronary events (MACE) over a year, Incidence of presumed metoprolol side-effects, Modified Medical Research Council dyspnea scale, Forced expiratory volume in one second (FEV1), Exercise capacity in six minutes (six-minute walk distance), San Diego Shortness of Breath Questionnaire, Combined rate of acute exacerbations of COPD and major adverse coronary events (MACE). Third, in part because the trial was stopped early, we had limited power to detect differences in the risk of severe exacerbation between subgroups and could not identify specific factors that predisposed patients to adverse outcomes when treated with metoprolol. According to this logic, Christopher mortality or all-cause hospitalization. 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. Clinicians need to be aware that bisoprolol loses its selectivity at 20 mg daily and metoprolol loses selectivity over 100 mg daily. Respir Med 2013;107:1376-1384. If correction for multiple comparisons was performed, the results would probably be deemed statistically insignificant. N Engl J Med 2011;365:689-698. Chen W, Thomas J, Sadatsafavi M, FitzGerald JM. there are a lot of secondary endpoints. It seems unlikely that the risks of worsening asthma or COPD outweigh the potential benefits of beta blocker use, in these patients. DOI: 10.1056/NEJMoa1908142, Tap into groundbreaking research and clinically relevant insights. The primary end point was the median time until the first COPD exacerbation of any severity during the treatment period, which was defined as the period from randomization to day 336 for the patients receiving a final dose of 25 mg of metoprolol or placebo or until day 350 for those receiving a dose of 50 mg or 100 mg. Characteristics of the Patients at Baseline. were enrolled if they had COPD and lacked Hankinson JL, Odencrantz JR, Fedan KB. 34. The primary endpoint wasmedian time until a COPD exacerbation. My preference is to use some judgement in these studies, based on numerous factors (e.g. I went to the doctor yesterday and he took me off the Metoprolol and put me on 100 mg of Losartan. S9). Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). study was designed to test the concept that beta-blockers could reduce the Gottlieb SS, McCarter RJ, Vogel RA. There was evidence that the metoprolol group had a higher rate of more severe exacerbation than the placebo group, with a rate ratio of 1.51 (95% CI, 1.00 to 2.29) for severe exacerbation and 3.71 (95% CI, 1.10 to 16.98) for very severe exacerbation (Table 2 and Fig. The — all in Minnesota; New York–Presbyterian (NYP)–Columbia University Medical Center (K.B. heart failure). Chest 1988;93:580-586. pre-test probability that the hypothesis is valid and the overall constellation of data findings). The trial was stopped early because of futility with respect to the primary end point and safety concerns. 21. Patients diagnosed with both heart failure (HF) and chronic obstructive pulmonary disease (COPD) treated with carvedilol may have a higher risk for hospitalization for HF compared with patients treated with metoprolol/bisoprolol/nebivolol, according to a … COPD and Beta-blockers: another myth dispensed…, IBCC chapter – Disseminated Intravascular Coagulation (DIC), PulmCrit- RCTs don't justify using convalescent plasma or antibody cocktails. ), NYP–Queens Medical Center (A.S.), and NYP–Brooklyn Methodist Medical Center (J.A.W.) 17. J Am Coll Cardiol 2012;60(24):e44-e164. 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 for the Prevention of Acute Exacerbations of COPD 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. Cardiovascular disease is a frequent comorbidity in patients with COPD. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351. In pts with CAD on BB, ie., metoprolol, with newly diagnosed severe COPD, what is the appropriate recommendation for BB therapy. A total of 532 patients underwent randomization. ); the Ann Arbor VA Medical Center (J.L.C.) Metoprolol copd. primary endpoint was time to first COPD exacerbation. An exacerbation of COPD was defined as an increase in or a new onset of two or more of the following symptoms: cough, sputum production, wheezing, dyspnea, or chest tightness that led to treatment with antibiotics or systemic glucocorticoids for at least 3 days.25,26 The severity of the exacerbation was graded according to the following scale: mild (involving only home management, with or without contact with a health care provider), moderate (leading to a visit to an emergency department), severe (leading to hospitalization), and very severe (leading to intubation and mechanical ventilation). 2. Eakin EG, Resnikoff PM, Prewitt LM, Ries AL, Kaplan RM. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. As Nonfatal and Fatal Serious Adverse Events. Cardioselective beta-blockers are generally safe among patients with COPD. In a randomized, double-blind, crossover trial, 40 CAD patients with mild COPD and significant reversibility received either bisoprolol 5 mg or atenolol 50 mg [ 84 ]. Smaller and less consistent effects were seen for systolic and diastolic blood pressure. Second, our trial population had moderate or severe COPD with a high prevalence of supplemental oxygen use and previous hospitalization for COPD. Unfortunately, this pattern shows no signs of abating today. Metoprolol zählt jedoch neben Bisoprolol, Nebivolol und Atenolol zu den selektiven Betablockern, welche nur am Herzen wirken: Damit ist der Wirkstoff auch für Asthma- und COPD-Patienten mit Herz-Kreislauf-Erkrankungen geeignet. Read More. 5. We excluded patients who had a proven indication for the use of a beta-blocker, including a history of myocardial infarction or revascularization within the previous 36 months or heart failure with a known left ventricular ejection fraction of less than 40%.23,24. 3. After the treatment period, there were 3 additional deaths in the metoprolol group (at 10 to 277 days after the last dose) and 4 additional deaths in the placebo group (at 10 to 26 days after the last dose). Some beta-adrenergic receptor blocking agents (i.e., beta-blockers) are contraindicated in patients with bronchial asthma or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease. From May 2016 through March 2019, a total of 532 patients underwent randomization (268 to the metoprolol group and 264 to the placebo group). 30. N Engl J Med 2014;370:2201-2210. Metoprolol for the Prevention of Acute Exacerbations of COPD. For severe or very severe exacerbations, the unadjusted and adjusted hazard ratios were 1.91 (95% CI, 1.29 to 2.83) and 2.08 (95% CI, 1.37 to 3.14), respectively (Figure 2B). Insbesondere bei höheren Dosierungen haben sie aber ebenfalls einen hemmenden Einfluss auf β 2-Rezeptoren. likelihood that the trial could possibly show benefit from metoprolol) and some concerns regarding safety. any indication for beta-blockers (e.g., prior myocardial infarction or systolic S8). BMC Pulm Med 2012;12:48-48. ); National Jewish Health, Denver (B.J.M. There were no significant between-group differences in several prespecified measurements, including the change from baseline in the FEV1, in the 6-minute walk distance, and in the score on the St. George’s Respiratory Questionnaire (Figs. They had a higher rate of COPD exacerbation within the year prior to study enrollment (63% vs. 50%, p=0.005). β-Blockers are associated with a reduction in COPD exacerbations. The majority of deaths in the metoprolol group were attributed to COPD (7, vs. 1 in the placebo group) (Table 3). Three beta blockers have demonstrated a survival benefit in systolic heart failure: the cardioselective agents metoprolol XL and bisoprolol, and the noncardioselective carvedilol. No commercial entity was involved in the trial. Many of them disappeared from the manuscript The primary endpoint was 12. Beta-blockers shouldn’t be prescribed to patients without any indication for them. Lancet Respir Med 2015;3:631-639. — both in Ann Arbor; the Cleveland Clinic, Cleveland (U.H. Dransfield MT, Rowe SM, Johnson JE, Bailey WC, Gerald LB. Miller MR, Crapo R, Hankinson J, et al. 19. 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. We did not observe this effect, and none was reported in a meta-analysis on the subject.35 We also found no evidence of between-group differences in the 6-minute walk distance or in patients’ reports of possible beta-blocker side effects. Copyright 2009-. 24. Metoprolol was associated with worsening of dyspnea and of the overall burden of COPD symptoms, as measured by the shortness-of-breath questionnaire and the COPD Assessment Test. Fourth, we do not know whether these results would be similar for other cardioselective beta-blockers or for noncardioselective agents, although concern regarding adverse respiratory effects is greater with the latter. Criner GJ, Connett JE, Aaron SD, et al. The hypothesis was based on non-causal associations of better outcome among patients who used beta-blockers, which, as usual, were then subject to further hypothetical pathophysiological explanations. Subsequently, some correlative data suggested that beta-blockers might be beneficial in COPD. COPD patients could also be included (code H3) if they have high reversibility. Albert RK, Connett J, Bailey WC, et al. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. Information and tools for librarians about site license offerings. Chest 2005;127:818-824. Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. However, this mortality difference doesn’t come anywhere close to Chest 2007;131:20-28. He is an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont. Interim analysis: the alpha spending function approach. Thus, we do not know whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk. Vogelmeier CF, Criner GJ, Martinez FJ, et al. We observed no evidence of between-group differences in the frequency of patient-reported adverse events that were potentially related to metoprolol (Table S3). Thisstudy was designed to test the concept that beta-blockers could reduce theincidence of COPD exacerbation. For fatal adverse events, the P value for the overall between-group comparison was calculated by the log-rank test; P=0.17 by Fisher’s exact test for the overall comparison among the causes of death. Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). Josh is the creator of PulmCrit.org. In this prospective, multicenter, randomized trial, we did not find evidence of a difference in the risk of COPD exacerbation between the metoprolol group and the placebo group, although the use of metoprolol was associated with a higher risk of exacerbation leading to hospitalization. ); Northwestern University, Chicago (R. Kalhan); the University of Vermont, Burlington (D.K. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group, with unadjusted and adjusted hazard ratios for death of 2.18 (95% CI, 0.76 to 6.29) and 2.13 (95% CI, 0.69 to 6.42), respectively (Fig. Es leite sich zwangsläufig die Empfehlung ab, keine Patienten mit Metoprolol zu behandeln, bei denen hierfür keine eindeutige Indikation bestehe, und insbesondere keine Hochrisiko-COPD-Patienten. The result of the subgroup analysis of the risk of exacerbation is provided in Figure S2. The median time until the first exacerbation was 202 days in the metoprolol group and 222 days in the placebo group. For a long time, there was a belief that beta-blockers were contraindicated in COPD. ¶ After the treatment period, three additional deaths occurred in the metoprolol group (two from COPD and one from pneumonia) and four in the placebo group (one from COPD, one from lung cancer, and two from unknown causes). The authorized source of trusted medical research and education for the Chinese-language medical community. Meguro M, Barley EA, Spencer S, Jones PW. Chest 1998;113:619-624. BMJ 2013;347:f6650-f6650. ), NYP–Weill Cornell Medical Center (R. Kaner, F.J.M. (Details regarding the power analyses are provided in the Supplementary Appendix, available at NEJM.org.) Su TH, Chang SH, Kuo CF, Liu PH, Chan YL. and six-minute walk distance). This site represents our opinions only. Nonfatal, serious COPD exacerbations occurred at a rate of 0.43 per person-year and 0.19 per person-year, respectively (Table 3 and Table S2). The patients in the metoprolol group had a greater increase (indicating worse control) from baseline in the score on the COPD Assessment Test than those in the placebo group, with a difference of 1.13 points (95% CI, 0.06 to 2.20) at day 112 and a difference of 1.47 points (95% CI, 0.32 to 2.62) at day 336 (Fig. This finding could explain why the effects of the cardioselective β-blocker metoprolol on AHR are the same as those of the nonselective β-blocker propranolol in patients with COPD .