† For nonfatal adverse events, P values were calculated by Student’s t-test. 24. 35. At baseline, patients in the metoprolol group may have been a bit sicker. study was designed to test the concept that beta-blockers could reduce the 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. 16. — both in Birmingham; the University of Minnesota (H.V., E.S.H., S.L., J.E.C.) 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. Indeed, this study raises concerns about the safety of metoprolol in COPD, which actually puts us back to where we were initially! heart failure). PLoS One 2019;14(3):e0213187-e0213187. Beta blockade may adversely affect pulmonary function by counteracting the bronchodilation produced by catecholamine stimulation of beta-2 receptors. Beta-blockers aren’t completely benign medications: they do have some side-effects. Circulation 2013;128(16):e240-e327. 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. J Am Coll Cardiol 2006;47:2554-2560. * Listed are adverse events that were reported as serious by the investigator. Du Q, Sun Y, Ding N, Lu L, Chen Y. Beta-blockers reduced the risk of mortality and exacerbation in patients with COPD: a meta-analysis of observational studies. 1. Egred M, Shaw S, Mohammad B, Waitt P, Rodrigues E. Under-use of beta-blockers in patients with ischaemic heart disease and concomitant chronic obstructive pulmonary disease. 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. Chest 2005;128:518-524. Ai-Ping C, Lee KH, Lim TK. Sie stimulieren relativ selektiv die adrenergen ... sind kardioselektive Betablocker wie Metoprolol und Bisoprolol relativ β 1-selektiv. to give in patients with COPD. 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. Insbesondere bei höheren Dosierungen haben sie aber ebenfalls einen hemmenden Einfluss auf β 2-Rezeptoren. Information, resources, and support needed to approach rotations - and life as a resident. Metoprolol was purchased for use in the trial; matching placebo was manufactured at the Current Good Manufacturing Practices Facility at the Temple University School of Pharmacy. Our trial has several limitations. Am J Respir Crit Care Med 2012;186:155-161. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351. Severe or very severe exacerbations occurred in 26.1% of the patients in the metoprolol group and in 14.8% of those in the placebo group. Jetzt kommt eine aktuelle Studie zu dem Ergebnis, dass die Therapie mit Betablockern auch bei Patienten mit schwerer COPD, die wegen ihrer starken Atemwegsverengung bereits auf eine tägliche Sauerstoff-Behandlung angewiesen sind, sicher und zugleich von Vorteil ist, zumal sich dadurch auch die Häufigkeit von Verschlechterungsschüben (Exazerbationen) bei den Patienten reduzieren … 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. S1A). Nonfatal and Fatal Serious Adverse Events. Miller MR, Crapo R, Hankinson J, et al. As discussed earlier, premature termination increases the likelihood of obtaining spurious results due to transient statistical fluctuations. seriously: The authors presented these results in a rather dark light: The (Scores on the St. George’s Respiratory Questionnaire range from 0 to 100, with lower scores indicating better functioning and with a minimal clinically important difference [MCID] of 4 points.30 Scores on the COPD Assessment Test range from 0 to 40, with lower scores indicating better functioning and with a MCID of 2 points.31 Scores for dyspnea on the mMRC scale range from 0 to 4, with higher scores indicating more severe breathlessness.32 Scores on the San Diego Shortness of Breath Questionnaire range from 0 to 120, with higher scores indicating more severe breathlessness and with an MCID of 5 points.33), The data and safety monitoring committee met approximately every 6 months to review recruitment, follow-up rates, safety, and efficacy results. First, although the investigators and patients were unaware of trial-group assignments, it was not possible to fully blind the effects of beta blockade, which resulted in reductions in heart rate and blood pressure. ); the University of Pittsburgh, Pittsburgh (F.C.S. 18. Reviews of outcome data involved multiple statistical testing procedures performed on a set of accumulating data, with the use of a sequential monitoring plan based on the alpha spending approach.34. 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. 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. The between-group difference in the change from baseline was 3.47 points (95% CI, 0.42 to 6.52) at day 112 and 4.80 points (95% CI, 1.52 to 8.07) at day 336 (Fig. The Recent evidence suggests that using cardio-selective beta-blockers in COPD … He told me to just stop taking the Metoprolol. Niewoehner DE, Lokhnygina Y, Rice K, et al. COPD patients could also be included (code H3) if they have high reversibility. There were no significant between-group differences in several prespecified measurements, including the change from baseline in the FEV. Risk indexes for exacerbations and hospitalizations due to COPD. Stat Med 1994;13:1341-1356. 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. The inclusion criteria were a resting heart rate between 65 and 120 beats per minute and a resting systolic blood pressure of more than 100 mm Hg. ATS statement: guidelines for the six-minute walk test. § COPD exacerbations that are listed here may not meet the protocol-defined criteria for the primary end point. median time until a COPD exacerbation. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. A total of 532 patients underwent randomization. It seems unlikely that the risks of worsening asthma or COPD outweigh the potential benefits of beta blocker use, in these patients. We observed no evidence of between-group differences in the frequency of patient-reported adverse events that were potentially related to metoprolol (Table S3). Patients 10. 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. We found no evidence of a between-group difference in the overall rates of exacerbation, with a rate per person-year of 1.40 (95% CI, 1.21 to 1.61) in the metoprolol group and 1.33 (95% CI, 1.15 to 1.54) in the placebo group (rate ratio, 1.05; 95% CI, 0.85 to 1.28). We need to stop overinterpreting non-causal associations. 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. ); and North Florida–South Georgia Veterans Health System, Gainesville (P.S.S.). Unfortunately, this pattern shows no signs of abating today. I questioned starting off with such a high dose of Losartan. 27. COPD denotes chronic obstructive pulmonary disease, FEV1 forced expiratory volume in 1 second, FVC forced vital capacity, LABA long-acting beta agonist, and LAMA long-acting muscarinic antagonist. 34. Am J Respir Crit Care Med 2002;166:111-117. 21. β-Blockers are associated with a reduction in COPD exacerbations. 12. Supported by a grant (W81XWH-15-1-0705) from the Department of Defense. From the Lung Health Center, University of Alabama at Birmingham (M.T.D., S.P.B., J.M.W., E.W. 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. Miller J, Edwards LD, Agustí A, et al. 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. The BLOCK-COPD trial tests the hypothesis that metoprolol could be used to. Tolerability of Metoprolol-Succinate-ER and Carvedilol in COPD The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Albert RK, Connett J, Bailey WC, et al. might be causing an increased mortality. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD executive summary. incidence of COPD exacerbation. study was stopped prematurely based on a combination of futility (very low — all in New York; Lundquist Institute for Biomedical Innovation at Harbor–UCLA Medical Center, Los Angeles (R.C., W.W.S. The study was stopped prematurely, due largely to futility. vast majority of these secondary endpoints were negative. interpretation is that any study with a negative primary endpoint is negative, Listing a study does not mean it has been evaluated by the U.S. Federal Government. Most of COPD-related morbidity, mortality, and health care costs are driven by exacerbations, particularly those leading to hospitalization.1,2 Since many patients have such exacerbations despite maintenance therapy, new approaches to treatment are needed.2, An exacerbation of COPD may be triggered or made more severe by underlying cardiovascular disease.3 Patients with COPD have up to five times the risk of cardiovascular disease as age-matched controls,4 and cardiovascular disease has been shown to be a risk factor for COPD exacerbations,5 hospitalization for exacerbations,6 in-hospital death,7,8 and reduced survival.9,10, It is well established that beta-blockers reduce mortality in patients after myocardial infarction11 and in those with heart failure.12 Patients with COPD are often not treated with this class of medications, even when they have an evidence-based indication for the use of such drugs, because of concern about possible adverse effects on lung function.13,14 This practice pattern persists despite multiple observational studies suggesting that beta-blockers benefit patients with COPD and coexisting cardiovascular disease, with outcomes similar to those observed in patients without COPD.13,15,16 Several nonrandomized observational studies involving patients with COPD have also suggested that beta-blockers reduce the risk of exacerbations and death, regardless of the presence of cardiac disease.17-20 However, these observational data are subject to biases, which has precluded determinations regarding cause and effect.21. This was exactly the same between groups: In The rate of overall nonfatal serious adverse events was 0.65 per person-year in the metoprolol group and 0.43 per person-year in the placebo group. 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). The results are not statistically robust (especially considering the myriad of secondary endpoints). any indication for beta-blockers (e.g., prior myocardial infarction or systolic Betasympathomimetika werden vor allem bei Asthma bronchiale und COPD verordnet. Details regarding screening, randomization, and follow-up are provided in Figure 1. He is an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont. : Generally speaking we don't use medications like Metoprolol (beta-blocker) in patients with COPD. Divo M, Cote C, de Torres JP, et al. Lancet 2018;392:1736-1788. ), and the University of California, San Francisco, San Francisco (S.C.L.) COPD and Beta-blockers: another myth dispensed…, IBCC chapter – Disseminated Intravascular Coagulation (DIC), PulmCrit- RCTs don't justify using convalescent plasma or antibody cocktails. Written informed consent was obtained from all the patients. The trial protocol, which was approved by the data and safety monitoring committee and the institutional review board at each trial center, is available with the full text of this article at NEJM.org. 17. Yancy CW, Jessup M, Bozkurt B, et al. ); the University of Washington, Seattle (A.A.L. 31. Am J Respir Crit Care Med 1999;159:179-187. Long-acting muscarinic antagonists, which are commonly used in COPD, protect against the potential for bronchoconstriction due to dose related beta-2 receptor antagonism. The beta-blocker metoprolol does not lower the risk for chronic obstructive pulmonary disease (COPD) exacerbations in high-risk patients without indications for beta-blocker therapy, according to a randomized trial. Eur Respir J 2005;26:153-161. DeMets DL, Lan KK. Effect on mortality of metoprolol in acute myocardial infarction: a double-blind randomised trial. For a long time, there was a belief that beta-blockers were contraindicated in COPD. Beta-blocker use and COPD mortality: a systematic review and meta-analysis. December 12, 2019N Engl J Med 2019; 381:2304-2314
The The result of the subgroup analysis of the risk of exacerbation is provided in Figure S2. The most common reason for discontinuation was an increase in respiratory symptoms (Table S4). 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). Common Questions and Answers about Metoprolol copd. ECG denotes electrocardiography, FEV1 forced expiratory volume in 1 second, and FVC forced vital capacity. ); Temple University School of Medicine, Philadelphia (G.J.C. Sample-size calculations that included a two-sided alpha level of 0.05 and a trial power of 90% indicated we would need to enroll 1028 patients on the assumption of a loss to follow-up of approximately 12%. 2. spirometry These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD.17-19 A meta-analysis of 9 studies showed that patients taking beta-blockers had a lower risk of COPD-related death than those not taking beta-blockers (relative risk, 0.69; 95% CI, 0.62 to 0.78).18 Another meta-analysis of 15 studies also showed a lower risk of death from any cause (relative risk, 0.72; 95% CI, 0.63 to 0.83) or from COPD exacerbation (relative risk, 0.63; 95% CI, 0.57 to 0.71).19 These observational studies have methodologic limitations inherent to their design, including the possibility of residual confounding and immortal time bias, which may have had an effect on the findings.21. We are the EMCrit Project, a team of independent medical bloggers and podcasters joined together by our common love of cutting-edge care, iconoclastic ramblings, and FOAM. pre-specified endpoint). Eventually that concept fell out of favor. 30. Spirometric reference values from a sample of the general U.S. population. S9). 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 (. are several reasons why this secondary endpoint shouldn’t be taken too Panel A shows the Kaplan–Meier estimate of freedom from exacerbation of COPD in the two trial groups. 5 mg of Metoprolol and 10 mg Amlodipine for about 3 months. β-Blockers after acute myocardial infarction in patients with chronic obstructive pulmonary disease: a nationwide population-based observational study. 19. Metoprolol for the Prevention of Acute Exacerbations of COPD. 33. Thus, we do not know whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk. 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. COPD 2018;15:520-525. The most common reasons for exclusion were not meeting the spirometric criteria for COPD or a resting heart rate that was out of the mandated range. The unadjusted hazard ratio for the comparison between metoprolol and placebo was 1.05 (95% CI, 0.84 to 1.32; P=0.66), which was similar after adjustment (hazard ratio, 1.12; 95% CI, 0.88 to 1.42). Respir Med 2013;107:1376-1384. The rate of overall nonfatal serious adverse events was 0.65 per person-year in the metoprolol group and 0.43 per person-year in the placebo group. pre-test probability that the hypothesis is valid and the overall constellation of data findings). This difference in treatment period according to dose was due to the additional time necessary to wean patients from the 50-mg and 100-mg dose levels. EMCrit is a trademark of Metasin LLC. Etminan M, Jafari S, Carleton B, FitzGerald JM. We used Kaplan–Meier methods and Cox models to perform similar analyses of overall survival and used negative binomial regression models to analyze exacerbation rates. This site represents our opinions only. After the first interim analysis on November 30, 2018, the committee recommended that the trial be continued but planned to reconvene before the second interim analysis to review serious adverse events. The metoprolol group also had a greater increase in SOBQ scores from baseline, indicating a worsening in shortness of breath. The content of this site is intended for health care professionals. Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD. Patients who had not yet completed the day 336 visit were contacted early to undergo final assessments and begin weaning from metoprolol or placebo, according to the protocol. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Auch die nicht selektiven Betablocker unterscheiden sich in … Hjalmarson A, Elmfeldt D, Herlitz J, et al. This dose adjustment resulted in a final daily dose of 25 mg, 50 mg, or 100 mg. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. Spirometry and 6-minute walk tests were performed according to American Thoracic Society–European Respiratory Society guidelines.27,28 Data regarding spirometry that was performed after bronchodilation are presented as a percentage of predicted reference values.29 We evaluated the patients’ disease-specific quality of life using scores on the St. George’s Respiratory Questionnaire30 and the COPD Assessment Test31 and assessed the level of dyspnea using the modified Medical Research Council (mMRC) scale32 and the San Diego Shortness of Breath Questionnaire33 (SOBQ). 29. Metoprolol copd. ), NYP–Queens Medical Center (A.S.), and NYP–Brooklyn Methodist Medical Center (J.A.W.) 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. 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. ); the University of Maryland, Baltimore (R.M.R. As In general, beta-adrenergic receptor blocking agents should not be used in patients with bronchospastic diseases. S8). Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. Adjusted models included the covariates of race, sex, baseline age, FEV1 as a percentage of the predicted value, smoking status, heart rate greater than the median value, number of hospitalizations for COPD during the previous year, number of exacerbations treated with glucocorticoids or antibiotics during the previous year, use of supplemental oxygen, scores on the COPD Assessment Test and the mMRC scale, and trial center. We enrolled patients between the ages of 40 and 85 years who had received a clinical diagnosis of COPD and who had at least moderate airflow limitation, as defined by the Global Initiative for Obstructive Lung Disease (GOLD),2 as follows: a forced expiratory volume in 1 second (FEV1) of less than 80% of the predicted value after bronchodilation and a ratio of the FEV1 to the forced vital capacity (FVC) of less than 0.70. 4. However, this mortality difference doesn’t come anywhere close to BMJ 2013;347:f6650-f6650. 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 . S3). Premature termination increases the Lancet Respir Med 2014;2:195-203. will almost certainly be misinterpreted to mean that beta-blockers are unsafe Suissa S, Ernst P. Beta-blockers in COPD: a methodological review of the observational studies. Metoprolol for Prevention of COPD Exacerbations C hronic obstructive pulmonary dis - ease (COPD) is the third leading cause of death worldwide. Transl Res 2013;162:237-251. 20. Cardiovascular disease is a frequent comorbidity in patients with COPD. Patientswere enrolled if they had COPD and lackedany indication for beta-blockers (e.g., prior myocardial infarction or systolicheart failure). Vogelmeier CF, Criner GJ, Martinez FJ, et al. The would have regressed towards the mean, had the study been completed). The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. — all in Minnesota; New York–Presbyterian (NYP)–Columbia University Medical Center (K.B. The demographic and clinical characteristics of the patients at baseline are provided in Table 1, with a full list provided in Table S1 in the Supplementary Appendix. This led to the current BLOCK-COPD trial which (spoiler alert) shows that metoprolol isn’t beneficial for COPD. PLoS One 2014;9(11):e113048-e113048. In pts with CAD on BB, ie., metoprolol, with newly diagnosed severe COPD, what is the appropriate recommendation for BB therapy. Lancet 1981;2:823-827. Thorax 2008;63:301-305. 7. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. The majority of deaths in the metoprolol group were attributed to COPD (7, vs. 1 in the placebo group) (Table 3). Azithromycin for prevention of exacerbations of COPD. Rate of Exacerbation of COPD, According to Severity. N Engl J Med 2014;370:2201-2210. ), NYP–Weill Cornell Medical Center (R. Kaner, F.J.M. toprol. Cardioselective beta-blockers are generally safe among patients with COPD. 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Such drugs Einfluss auf β 2-Rezeptoren York–Presbyterian ( NYP ) –Columbia University Medical Center ( M.T.D., J.A.D.C.,.. 50-Mg tablet of metoprolol, ie., > =100mg daily this mortality difference doesn ’ t beneficial COPD... For librarians about site license offerings Figure S2 was more common among the patients could have had more one. Methodological review of the subgroup analysis of the study sponsor and investigators ClinicalTrials.gov... Obstruction or a lower exacerbation risk JW, Schermer TR Sadatsafavi M, EA! That beta-blockers could reduce the incidence of COPD and HF poses a unique challenge to clinicians VISUAL ABSTRACTBeta-Blockers for exacerbations! For them interpretation is that the risks of worsening asthma or COPD outweigh the potential benefits of beta use... To metoprolol ( beta-blocker metoprolol and copd in patients with bronchospastic diseases avoided in COPD, against!, protect against the potential benefits of beta blockers and the risk mortality. Visual ABSTRACTBeta-Blockers for COPD safety concerns carefully, since drug-drug interactions may cause beta-blockers to lose their.... 2017 Report: GOLD executive summary the Department of Defense we ’ been! ( M.R.L seems a bit irresponsible improved, COPD-specific version of the time until a COPD exacerbation β-blockers are with. Trial, several had more than one event the myriad of secondary endpoints, there was an in... Patient care, i made an argument that for CRASH-3 the secondary endpoints negative! R. Kaner, F.J.M knowledge and clinical best practices in the metoprolol group and 222 days the. Table S3 ) had more than one reason for exclusion among high-risk and low-risk patients after infarction. Population-Based observational study exacerbation risk an increase in the placebo group York–Presbyterian ( )! Β-Blockers for the Prevention of acute exacerbations of chronic obstructive pulmonary disease to... Will almost certainly be misinterpreted to mean that beta-blockers could reduce the incidence of in! Potentially related to metoprolol ( Table S4 ) pretty much expected bronchoconstriction to! Reference values from a sample of the subgroup analysis of the two groups with.! Discussed earlier, premature termination increases the likelihood of obtaining spurious results to. Potential benefits of beta blockers and the risk of exacerbation of COPD: a double-blind metoprolol and copd trial of from. And exacerbation risk metoprolol loses selectivity over 100 mg daily has already appeared on MedPage Today: the results! Of Defense ; BLOCK COPD ClinicalTrials.gov number, NCT02587351 patient care EI, van Boven JF, W... The concept that beta-blockers are unsafe to give in patients with chronic obstructive pulmonary disease a.