Chest 1998;113:619-624. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. 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. 35. 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. 23. Beta-blockers shouldn’t be prescribed to patients without any indication for them. The use of beta-blockers in COPD has been subject to repeated reversals over the past few decades. For a long time, there was a belief that beta-blockers were contraindicated in COPD. β-Blockers are associated with a reduction in COPD exacerbations. 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 ]. 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. Objective measurements of lung function were the same (e.g. 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. 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. No commercial entity was involved in the trial. This article was published on October 20, 2019, at NEJM.org. Nonfatal and Fatal Serious Adverse Events. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 2006;47:2554-2560. Transl Res 2013;162:237-251. Information, resources, and support needed to approach rotations - and life as a resident. 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 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. The rate of hospitalization for any cause was 0.66 per person-year (95% CI, 0.47 to 0.86) in the metoprolol group and 0.42 per person-year (95% CI, 0.30 to 0.55) in the placebo group. Su TH, Chang SH, Kuo CF, Liu PH, Chan YL. trend in mortality is mentioned here, which seems to imply that metoprolol Unfortunately, this pattern shows no signs of abating today. ); and North Florida–South Georgia Veterans Health System, Gainesville (P.S.S.). If correction for multiple comparisons was performed, the results would probably be deemed statistically insignificant. Metoprolol was well tolerated for 3 months by 50 patients with coexistent CAD and mild to severe COPD. 34. Betasympathomimetika werden vor allem bei Asthma bronchiale und COPD verordnet. In a murine model of antigen-induced airway inflammation and AHR, duration of therapy was the determinant of response to β-AR ligands . : Generally speaking we don't use medications like Metoprolol (beta-blocker) in patients with COPD. median time until a COPD exacerbation. Chest 2007;132:456-463. Rate of Exacerbation of COPD, According to Severity. Sorry, your blog cannot share posts by email. Beta-blockers are safe for most patients with asthma and COPD? Am J Respir Crit Care Med 2002;166:111-117. From the Lung Health Center, University of Alabama at Birmingham (M.T.D., S.P.B., J.M.W., E.W. were enrolled if they had COPD and lacked 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. Clinicians also need to monitor these patients carefully, since drug-drug interactions may cause beta-blockers to lose their cardio-selectivity. S1A). Should patient be tapered and switched to diltiazem/verapamil or continued? Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. The results are not statistically robust (especially considering the myriad of secondary endpoints). and six-minute walk distance). Address reprint requests to Dr. Dransfield at the University of Alabama at Birmingham, 422 Tinsley Harrison Tower, 1900 University Blvd., Birmingham, AL 35294, or at [email protected]. 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. 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 … Mahler DA, Wells CK. § COPD exacerbations that are listed here may not meet the protocol-defined criteria for the primary end point. toprol. 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. ), the University of California, San Francisco–Fresno, Fresno (V.V.J. † For nonfatal adverse events, P values were calculated by Student’s t-test. S1B). 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. Evaluation of clinical methods for rating dyspnea. 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. are several reasons why this secondary endpoint shouldn’t be taken too Randomization was performed by a computer algorithm by means of an interactive website linked to the data coordinating center. (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. Subsequently, some correlative data suggested that beta-blockers could reduce the incidence of COPD and HF poses a unique to... 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