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Q:Can Patients with COPD Or Asthma 1-MINUTE CONSULT BRI EF ANSWERS TO SPECIFIC CLINICAL QUESTIONS Q: Can patients with COPD or asthma take a beta-blocker? ELSY VIVIANA NAVAS, MD duction in mortality rates in patients with con- Department of Cardiovascular Medicine, Cleveland Clinic ditions often considered a contraindication to DA VID O. TAYLOR, MD beta-blocker therapy, such as congestive heart Department of Cardiovascular Medicine, Critical Care Center, failure, pulmonary disease, and older age.5 and Transplantation Center, Cleveland Clinic Yes. Treatment with beta-adrenergic ■ AC RDIOSELECTIVE BETA-BLOCKERS A: receptor blockers decreases the mortal- ity rate in patients with coronary artery disease Cardioselective beta-blockers with an affinity or heart failure, as well as during the periopera- for the beta-1 receptor theoretically result in tive period in selected patients (eg, those with fewer adverse effects on the lungs. They com- a history of myocardial infarction, a positive petitively block the response to beta-adrenergic stress test, or current chest pain due to myocar- stimulation and selectively block beta-1 recep- dial ischemia). The current evidence supports tors with little or no effect on beta-2 receptors, giving beta-blockers to patients with coronary except perhaps at high doses. However, this artery disease and chronic obstructive pulmo- possible high-dose effect requires further study. Beta-blockers nary disease (COPD) or asthma, which lowers The effect of cardioselective beta-blockers may increase the 1-year mortality rate to a degree similar to on respiratory function was evaluated in two that in patients without COPD or asthma, and meta-analyses,6,7 one in patients with mild to airway without worsening respiratory function.1 How- moderate reactive airway disease, the other in reactivity and ever, many clinicians still hesitate to start pa- patients with mild to severe COPD. Patients bronchospasm, tients with COPD or asthma on a beta-blocker with reactive airway disease who received a due to the fear of bronchoconstriction.2 single dose of a beta-blocker had a 7.46% re- but not giving duction in forced expiratory volume in the first one can pose a ■ THE RISKS second of expiration (FEV1), an effect that was completely reversed by treatment with a beta- risk of death In patients with reversible airway disease, beta- agonist inhaler. The FEV1 increased by a statis- blockers may increase airway reactivity and tically significantly greater amount in response bronchospasm, as well as decrease the response to beta-agonists in patients who received beta- to inhaled or oral beta-receptor agonists.3 Even blockers (a single dose or continuous therapy) topical ophthalmic nonselective beta-blockers than in those who did not receive beta-block- for glaucoma can cause a worsening of pulmo- ers. Patients who received continuous cardiose- nary function.4 However, these data are from lective beta-blockers experienced no significant small trials in the 1970s and 1980s. drop in FEV1, and no new symptoms developed. On the other hand, not giving beta-block- These results led the authors to conclude that ers can pose a risk of death. In a retrospective cardioselective beta-blockers do not cause a study of more than 200,000 patients with myo- significant reduction in pulmonary function in cardial infarction, Gottlieb et al5 found that patients with mild to moderate reactive airway beta-blockers were associated with a 40% re- disease and COPD and are therefore safe to use. A single dose of a cardioselective beta-blocker doi:10.3949/ccjm.77a.09133 may produce a small decrease in FEV1, especial- 498 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 • NUMBER 8 AUGUST 2010 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. NAVAA S ND TAYLOR ly in patients with reactive airway disease, but as therapy TABLE 1 is continued over days to weeks, there is no significant change in symptoms or FEV1 and no increase in the need Categories and examples of beta-blockers for beta-agonist inhalers. A major limitation of the two meta-analyses was N onselective Selective beta-blockers that the patients were younger than most patients beta-blockers (beta-1-receptor blockers) Nadolol (Corgard) Acebutolol (Sectral) who require beta-blockers: the average age was 40 in Penbutolol (Levatol) Atenolol (Tenormin) patients with reactive airway disease, and 54 in pa- Pindolol (Visken) Betaxolol (Kerlone) tients with COPD. Also important to consider is that Propranolol (Inderal) Bisoprolol (Zebeta) only patients with mild to moderate reactive airway Sotalol (Betapace) Esmolol (Brevibloc) disease were included. Patients with severe asthma, Timolol (Blocadren) Metoprolol (Toprol) especially those with active bronchospasm, may react Nebivolol (Bystolic) differently to even cardioselective beta-blockers. Combined nonselective alpha- and beta-blockers (cardioselective) ■ NONSELECTIVE BETA-BLOCKERS Carvedilol (Coreg) Labetalol (Trandate) Recent studies suggest that nonselective beta-blockers can affect respiratory function in patients with COPD, but they have failed to show any harm. For example, propranolol (Inderal) was shown to worsen pulmonary ■ OUR RECOMMENDATIONS function and to decrease the sensitivity of the airway to the effects of long-acting beta-2-agonists, but the Beta-blockers improve survival rates in patients 15 patients included in this study had no increase in with chronic systolic heart failure and after myo- respiratory symptoms.8 cardial infarction, including in those patients with It has also been suggested that combined nonse- coexisting COPD and reactive airway disease. But lective beta- and alpha-receptor blockade—eg, with not all beta-blockers are the same (TABLE 1). Cardi- labetalol (Trandate) or carvedilol (Coreg)—might be oselective beta-blockers (ie, those that block pre- better tolerated than nonselective beta-blockers in pa- dominantly beta-1 receptors) are our beta-blockers tients with COPD.9 However, from limited data, Kot- of choice based on stronger evidence from clinical lyar et al10 suggested that carvedilol may be less well studies. Nonselective agents that include alpha-ad- tolerated in patients with asthma than with COPD. renergic blockade can be considered, although less All current evidence on combined nonselective beta- is known about their effect on respiratory function. and alpha-blockade is observational, and it is not yet However, the use of even beta-1-selective drugs clear whether this class of beta-blockers is better toler- merits caution and close follow-up in patients with ated due to alpha-blockade or merely because nonse- severe asthma (for which clinical study data are lective beta-blockers themselves are well tolerated. limited). ■ meta-analysis. Respir Med 2003; 97:1094–1101. ■ CREFEREN ES 7. Salpeter SR, Ormiston TM, Salpeter EE. Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis. Ann Intern . 1 Chen J, Radford MJ, Wang Y, Marciniak TA, Krumholz HM. Effective- Med 2002; 137:715–725. ness of beta-blocker therapy after acute myocardial infarction in el- 8. van der Woude HJ, Zaagsma J, Postma DS, Winter TH, van Hulst M, derly patients with chronic obstructive pulmonary disease or asthma. Aalbers R. Detrimental effects of beta-blockers in COPD: a concern J Am Coll Cardiol 2001; 37:1950–1956. for nonselective beta-blockers. Chest 2005; 127:818–824. 2. The sixth report of the Joint National Committee on prevention, 9. Sirak TE, Jelic S, Le Jemtel TH. Therapeutic update: non-selective detection, evaluation, and treatment of high blood pressure. Arch beta- and alpha-adrenergic blockade in patients with coexistent Intern Med 1997; 157:2413–2446. chronic obstructive pulmonary disease and chronic heart failure. J 3. Benson MK, Berrill WT, Cruickshank JM, Sterling GS. A comparison of Am Coll Cardiol 2004; 44:497–502. four beta-adrenoceptor antagonists in patients with asthma. Br J Clin 10. Kotlyar E, Keogh AM, Macdonald PS, Arnold RH, McCaffrey DJ, Pharmacol 1978; 5:415–419. Glanville AR. Tolerability of carvedilol in patients with heart failure 4. Fraunfelder FT, Barker AF. Respiratory effects of timolol. N Engl J and concomitant chronic obstructive pulmonary disease or asthma. J Med 1984; 311:1441. Heart Lung Transplant 2002; 21:1290–1295. 5. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998; 339:489–497. ADDRESS: David O. Taylor, MD, Department of Cardiovascular Medicine, 6. Salpeter SR, Ormiston TM, Salpeter EE, Poole PJ, Cates CJ. Cardio- J3, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail selective beta-blockers for chronic obstructive pulmonary disease: a [email protected]. CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 77 • NUMBER 8 AUGUST 2010 499 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. 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