BMJ  1993;306:1034-1037 (17 April), doi:10.1136/bmj.306.6884.1034

Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.

Glaxo Group Research, Greenford, Middlesex.

OBJECTIVE--To compare safety of salmeterol and salbutamol in treating asthma. DESIGN--Double blind, randomised clinical trial in parallel groups over 16 weeks. SETTING--General practices throughout the United Kingdom. SUBJECTS--25,180 patients with asthma considered to require regular treatment with bronchodilators who were recruited by their general practitioner (n = 3516). INTERVENTIONS--Salmeterol (Serevent) (50 micrograms twice daily) or salbutamol (200 micrograms four times a day) randomised in the ratio of two patients taking salmeterol to one taking salbutamol. All other drugs including prophylaxis against asthma were continued throughout the study. MAIN OUTCOME MEASURES--All serious events and reasons for withdrawals (medical and non-medical) whether or not they were considered to be related to the drugs. RESULTS--Fewer medical withdrawals due to asthma occurred in patients taking salmeterol than in those taking salbutamol (2.91% v 3.79%; chi 2 = 13.6, p = 0.0002). Mortality and admissions to hospital were as expected. There was a small but non-significant excess mortality in the group taking salmeterol and a significant excess of asthma events including deaths in patients with severe asthma on entry. Use of more than two canisters of bronchodilator a month was particularly associated with the occurrence of an adverse asthma event. CONCLUSIONS--Treatment over 16 weeks with either salmeterol or salbutamol was not associated with an incidence of deaths related to asthma in excess of that predicted. Overall control of asthma was better in patients allocated to salmeterol. Serious adverse events occurred in patients most at risk on entry and were probably due to the disease rather than treatment.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    What's this?

Relevant Articles

Bronchodilator treatment in asthma. Manufacturers underestimate mortality from asthma.

W H Inman
BMJ 1993 306: 1610-1611. [PDF]

Bronchodilator treatment in asthma. Study too small to detect increase in deaths.

R Bunney
BMJ 1993 306: 1610-1611. [PDF]

Bronchodilator treatment in asthma. Regular treatment with beta agonists remains unevaluated.

G K Crompton
BMJ 1993 306: 1610-1611. [PDF]

Bronchodilator treatment in asthma. Increase in deaths during salmeterol treatment unexplained.

M R Sears and D R Taylor
BMJ 1993 306: 1610-1611. [PDF]

This article has been cited by other articles:

• Wijesinghe, M., Weatherall, M., Perrin, K., Harwood, M., Beasley, R. (2009). Risk of mortality associated with formoterol: a systematic review and meta-analysis. Eur Respir J 34: 803-811 [Abstract] [Full text]  
• Lommatzsch, M, Lindner, Y, Edner, A, Bratke, K, Kuepper, M, Virchow, J C (2009). Adverse effects of salmeterol in asthma: a neuronal perspective. Thorax 64: 763-769 [Abstract] [Full text]  
• Sears, M. R. (2009). Safety of Long-Acting {beta}-Agonists: Are New Data Really Required?. Chest 136: 604-607 [Abstract] [Full text]  
• Wijesinghe, M., Weatherall, M., Perrin, K., Crane, J., Beasley, R. (2009). International Trends in Asthma Mortality Rates in the 5- to 34-Year Age Group: A Call for Closer Surveillance. Chest 135: 1045-1049 [Abstract] [Full text]  
• Beasley, R., Martinez, F. D., Hackshaw, A., Rabe, K. F., Sterk, P. J., Djukanovic, R. (2009). Safety of long-acting {beta}-agonists: urgent need to clear the air remains. Eur Respir J 33: 3-5 [Full text]  
• Sears, M. R., Ottosson, A., Radner, F., Suissa, S. (2009). Long-acting {beta}-agonists: a review of formoterol safety data from asthma clinical trials. Eur Respir J 33: 21-32 [Abstract] [Full text]  
• Jaeschke, R., O'Byrne, P. M., Mejza, F., Nair, P., Lesniak, W., Brozek, J., Thabane, L., Cheng, J., Schunemann, H. J., Sears, M. R., Guyatt, G. (2008). The Safety of Long-Acting {beta}-Agonists among Patients with Asthma Using Inhaled Corticosteroids: Systematic Review and Metaanalysis. Am. J. Respir. Crit. Care Med. 178: 1009-1016 [Abstract] [Full text]  
• Wijesinghe, M, Perrin, K, Harwood, M, Weatherall, M, Beasley, R (2008). The risk of asthma mortality with inhaled long acting {beta}-agonists. Postgrad. Med. J. 84: 467-472 [Abstract] [Full text]  
• Weiss, K. B. (2008). Drug Safety and Salmeterol: The Controversy Continues. ANN INTERN MED 149: 56-57 [Full text]  
• Cazzola, M., Matera, M. G. (2007). Review: Safety of long-acting {beta}2 -agonists in the treatment of asthma. Ther Adv Respir Dis 1: 35-46 [Abstract]  
• Black, P. N., Chen, R., Zitt, M. J., Rachelefsky, G. S., Peters, S. P., Castro, M., Holbrook, J. T. (2007). Reducing Asthma Treatment. NEJM 357: 504-506 [Full text]  
• Salpeter, S. R. (2007). Should we avoid {beta}-agonists for moderate and severe chronic obstructive pulmonary disease?: YES. cfp 53: 1290-1293 [Full text]  
• Salpeter, S. R. (2007). Faut-il eviter les -agonistes dans les cas de bronchopneumopathies chroniques obstructives moderees et graves?: OUI. cfp 53: 1294-1297 [Full text]  
• Bell, A. D., McIvor, R. A. (2007). The SMART study. cfp 53: 687-688 [Full text]  
• Deykin, A., Wechsler, M. E., Boushey, H. A., Chinchilli, V. M., Kunselman, S. J., Craig, T. J., DiMango, E., Fahy, J. V., Kraft, M., Leone, F., Lazarus, S. C., Lemanske, R. F. Jr., Martin, R. J., Pesola, G. R., Peters, S. P., Sorkness, C. A., Szefler, S. J., Israel, E., for the National Heart, Lung, and Blood Institute', (2007). Combination Therapy with a Long-Acting beta-Agonist and a Leukotriene Antagonist in Moderate Asthma. Am. J. Respir. Crit. Care Med. 175: 228-234 [Abstract] [Full text]  
• Hasford, J., Virchow, J. C. (2006). Excess mortality in patients with asthma on long-acting {beta}2-agonists.. Eur Respir J 28: 900-902 [Full text]  
• Sears, M. R., Nelson, H. S., Dorinsky, P. M. (2006). The salmeterol multicenter asthma research trial.. Chest 130: 928-929 [Full text]  
• Seymour, S. M., Sullivan, E. J., Chowdhury, B. A., Meyer, R. J., Davi, R. C., Nelson, H. S., Dorinsky, P. M. (2006). Comments on the salmeterol multicenter asthma research trial.. Chest 130: 930-931 [Full text]  
• Vassiliou, V., Zipitis, C. S (2006). Long-acting bronchodilators: time for a re-think.. JRSM 99: 382-383 [Full text]  
• Glassroth, J. (2006). The Role of Long-Acting {beta}-Agonists in the Management of Asthma: Analysis, Meta-Analysis, and More Analysis. ANN INTERN MED 144: 936-937 [Full text]  
• Giembycz, M. A., Newton, R. (2006). Beyond the dogma: novel {beta}2-adrenoceptor signalling in the airways.. Eur Respir J 27: 1286-1306 [Abstract] [Full text]  
• Williams, D. M. (2006). Considerations in the long-term management of asthma in ambulatory patients. Am J Health Syst Pharm 63: S14-S21 [Abstract] [Full text]  
• Mintz, M. L., O'Connor, G. T., Martinez, F. D. (2006). Safety of long-acting beta-agonists.. NEJM 354: 1206-1208 [Full text]  
• Wechsler, M. E., Lehman, E., Lazarus, S. C., Lemanske, R. F. Jr., Boushey, H. A., Deykin, A., Fahy, J. V., Sorkness, C. A., Chinchilli, V. M., Craig, T. J., DiMango, E., Kraft, M., Leone, F., Martin, R. J., Peters, S. P., Szefler, S. J., Liu, W., Israel, E., for the National Heart Lung and Blood Institute's, (2006). beta-Adrenergic Receptor Polymorphisms and Response to Salmeterol. Am. J. Respir. Crit. Care Med. 173: 519-526 [Abstract] [Full text]  
• O'Byrne, P. M., Adelroth, E. (2006). {beta}2 Deja Vu. Chest 129: 3-5 [Full text]  
• Nelson, H. S., Weiss, S. T., Bleecker, E. R., Yancey, S. W., Dorinsky, P. M., the SMART Study Group, (2006). The Salmeterol Multicenter Asthma Research Trial: A Comparison of Usual Pharmacotherapy for Asthma or Usual Pharmacotherapy Plus Salmeterol. Chest 129: 15-26 [Abstract] [Full text]  
• Martinez, F. D. (2005). Safety of Long-Acting Beta-Agonists -- An Urgent Need to Clear the Air. NEJM 353: 2637-2639 [Full text]  
• Wooltorton, E. (2005). Long-acting {beta}2-agonists in asthma: safety concerns. CMAJ 173: 1030-1031 [Full text]  
• Ioannidis, J. P.A., Evans, S. J.W., Gotzsche, P. C., O'Neill, R. T., Altman, D. G., Schulz, K., Moher, D., for the CONSORT Group*, (2004). Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement. ANN INTERN MED 141: 781-788 [Abstract] [Full text]  
• Mann, M., Chowdhury, B., Sullivan, E., Nicklas, R., Anthracite, R., Meyer, R. J. (2003). Serious Asthma Exacerbations in Asthmatics Treated With High-Dose Formoterol. Chest 124: 70-74 [Abstract] [Full text]  
• (1997). Using {beta}2-stimulants in asthma. DTB 35: 1-4 [Abstract] [Full text]  
• Busse, W. W. (1996). Long- and Short-Acting {beta}2-Adrenergic Agonists: Effects on Airway Function in Patients With Asthma. Arch Intern Med 156: 1514-1520 [Abstract]  

Online poll

Find out more here>> and here>>