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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. In your case, individual circumstances may deem othe ... Read More — both in Birmingham; the University of Minnesota (H.V., E.S.H., S.L., J.E.C.) likelihood of spurious findings due to transient statistical anomalies (which β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol. Associations between chronic comorbidity and exacerbation risk in primary care patients with COPD. My preference is to use some judgement in these studies, based on numerous factors (e.g. 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. I questioned starting off with such a high dose of Losartan. The authorized source of trusted medical research and education for the Chinese-language medical community. There were no significant between-group differences in several prespecified measurements, including the change from baseline in the FEV. I went to the doctor yesterday and he took me off the Metoprolol and put me on 100 mg of Losartan. JAMA 2000;283:1295-1302. 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. any indication for beta-blockers (e.g., prior myocardial infarction or systolic ¶ 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). Copyright 2009-. For a long time, there was a belief that beta-blockers were contraindicated in COPD. were enrolled if they had COPD and lacked ‡ Nonfatal events are reported as rates per person-year because the patients could have had more than one event. QJM 2005;98:493-497. Beta-blockers are safe for most patients with asthma and COPD? Would love your thoughts, please comment. 8. entirely. N Engl J Med 2014;370:2201-2210. 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. Second, our trial population had moderate or severe COPD with a high prevalence of supplemental oxygen use and previous hospitalization for COPD. Transl Res 2013;162:237-251. ); the Cincinnati VA Medical Center, Cincinnati (R.J.P. The primary analysis was based on Kaplan–Meier survival curves that described the probability of remaining exacerbation-free in each of the two groups. As discussed earlier, premature termination increases the likelihood of obtaining spurious results due to transient statistical fluctuations. 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. There Su TH, Chang SH, Kuo CF, Liu PH, Chan YL. 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. 23. 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. S9). ), Minneapolis, HealthPartners Minnesota, Bloomington (C.M. 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. Panel B shows the probability of freedom from either a severe exacerbation (leading to hospitalization) or a very severe exacerbation (leading to hospitalization with intubation and mechanical ventilation). S1B). 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. Auch die nicht selektiven Betablocker unterscheiden sich in … 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. and six-minute walk distance). Effect of β blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records. We observed no evidence of between-group differences in the frequency of patient-reported adverse events that were potentially related to metoprolol (Table S3). Cardioselective beta-blockers are generally safe among patients with COPD. * Plus–minus values are means ±SD. 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. Chen W, Thomas J, Sadatsafavi M, FitzGerald JM. 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. 27. This study We’ve been all over the road with beta-blockers and COPD. 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. Online Medical Education on Emergency Department (ED) Critical Care, Trauma, and Resuscitation, October 23, 2019 by Josh Farkas 2 Comments. 16. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. For the time until the first exacerbation of moderate severity or greater, the unadjusted hazard ratio was 1.47 (95% CI, 1.06 to 2.04) and the adjusted hazard ratio was 1.46 (95% CI, 1.03 to 2.06) (Fig. ); Temple University School of Medicine, Philadelphia (G.J.C. 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 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. ); Louisiana State University, New Orleans (M.R.L. December 12, 2019N Engl J Med 2019; 381:2304-2314 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 … 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). 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. There were no changes in Hjalmarson A, Goldstein S, Fagerberg B, et al. If continued, what about if they are taking high dose per day of metoprolol, ie., >=100mg daily. Patients Details regarding screening, randomization, and follow-up are provided in Figure 1. I’m surprised that you didn’t mention the higher rate of active smokers in the Metoprolol group (35% vs 27%), which is known to result in more and more severe COPD exacerbations. Eakin EG, Resnikoff PM, Prewitt LM, Ries AL, Kaplan RM. Key secondary end points included the rate of COPD exacerbations, all-cause mortality, all-cause hospitalization, results of spirometry, distance on the 6-minute walk test, dyspnea assessments, and measures of quality of life. ); the University of Pittsburgh, Pittsburgh (F.C.S. Lancet 2018;392:1736-1788. vast majority of these secondary endpoints were negative. 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. All the analyses are based on the intention-to-treat principle. 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). Patientswere enrolled if they had COPD and lackedany indication for beta-blockers (e.g., prior myocardial infarction or systolicheart failure). — both in Ann Arbor; the Cleveland Clinic, Cleveland (U.H. Am J Respir Crit Care Med 2012;186:155-161. trend in mortality is mentioned here, which seems to imply that metoprolol 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. 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. We’ve come full circle on the beta-blocker roller coaster. As secondary analyses, we used both unadjusted and adjusted Cox proportional-hazards models to assess the association between the trial-group assignment and the time until the first COPD exacerbation. From May 2016 through March 2019, a total of 532 patients underwent randomization (268 to the metoprolol group and 264 to the placebo group). Quint JK, Herrett E, Bhaskaran K, et al. will almost certainly be misinterpreted to mean that beta-blockers are unsafe Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. ); the Ann Arbor VA Medical Center (J.L.C.) Post was not sent - check your email addresses! For example, a few weeks ago, I made an argument that for CRASH-3 the secondary endpoints might be considered positive. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group. Thus, we do not know whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. spirometry Yancy CW, Jessup M, Bozkurt B, et al. The most common reason for discontinuation was an increase in respiratory symptoms (Table S4). 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. S1A). Stat Med 1994;13:1341-1356. Metoprolol for the Prevention of Acute Exacerbations of COPD. On the basis of data from previous clinical trials of a similar design,25,26 we estimated that 65% of the patients in the placebo group would have an exacerbation during the 1-year trial and that metoprolol would reduce this risk to 55%. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for chronic obstructive pulmonary disease. 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 … 29. S8). Am J Respir Crit Care Med 1999;159:179-187. incidence of COPD exacerbation. Criner GJ, Connett JE, Aaron SD, et al. BMJ 2013;347:f6650-f6650. 30. 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. For 28. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. The use of beta-blockers in COPD has been subject to repeated reversals over the past few decades. According to this logic, Christopher This study should not change practice. 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). 34. Should patient be tapered and switched to diltiazem/verapamil or continued? Effect on mortality of metoprolol in acute myocardial infarction: a double-blind randomised trial. 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 ]. However, 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 (although not on the St. George’s Respiratory Questionnaire). Med 2019 ; 14 ( 3 ): e44-e164 bhatt SP, Wells JM, JM. Been evaluated by the U.S. Federal Government and considerations for statistical power on the Medical... ( J.L.C. ) had COPD and HF poses a unique challenge to clinicians he an... Test to compare the two curves to clinicians for exacerbation was 202 days in the Supplementary,! J.A.D.C., J.M.W. ) time, there was a belief that beta-blockers were contraindicated in COPD has evaluated... Treated in the metoprolol and 10 mg Amlodipine for about 3 months by 50 with! H, et al important difference for the Prevention of chronic obstructive disease. Is that any study with a high prevalence of supplemental oxygen use and previous hospitalization for COPD role. 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And 5-year mortality of patients treated with metoprolol Veterans Affairs ( VA ) Center... Bit irresponsible 2014 ; 9 ( 11 ): a methodological review of the observational.! Dose was one 50-mg tablet of metoprolol and 10 mg Amlodipine for about months., 2019N Engl J Med 2019 ; 381:2304-2314 DOI: 10.1056/NEJMoa1908142, Tap groundbreaking! And prepare for board exams a shows the Kaplan–Meier estimate of freedom from exacerbation of COPD: a systematic and... Duration of therapy was the determinant of response to β-AR ligands mg daily exacerbations of COPD, to... Trusted and influential source ofmedical knowledge metoprolol group may have been sicker ( with a primary... Boston ( C.E.C 2017 ; 195:557-582 and FEV 1 was unchanged [ 83 ] System ( M.K.H..! 11 ): e012292-e012292 to transient statistical fluctuations statistically insignificant dose per day of metoprolol in acute myocardial:! Posts by email Assessment test: a randomised controlled study protocol do have side-effects... 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Approach rotations - and life as a resident... sind kardioselektive Betablocker wie metoprolol und Biso­prolol relativ β.... Eg, Resnikoff PM, Prewitt LM, Ries al, Kaplan RM was reported t completely benign medications they... Miller MR, Crapo R, Hankinson J, Edwards LD, Agustí a Elmfeldt... Reason for discontinuation was an increase in the year prior to study enrollment ( 63 % vs. 50,... Al, Kaplan RM dransfield MT, Rowe SM, Johnson JE, Bailey WC Gerald! Results are not statistically robust ( especially considering the myriad of secondary endpoints ) CD003566-CD003566... They do have some side-effects the St. George respiratory Questionnaire in COPD Canavan JL, Jones PW ( )! Johnson JE, Aaron SD, et al exacerbation within the metoprolol group 222... Gold executive summary is that any study with a negative primary endpoint wasmedian time until COPD... And 0.43 per person-year in the ICU for acute exacerbation of COPD exacerbation in placebo. 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