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Age- and Gender-Specific Asthma Death Rates in Patients Taking Long-Acting β2-Agonists

Prescription Event Monitoring Pharmacosurveillance Studies

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Abstract

Objective: Prescription event monitoring is a national drug safety surveillance scheme in which prescribers are prompted to report events and deaths following prescription of newly marketed drugs. This paper presents age- and gender-specific asthma death rates in patients prescribed the long-acting β2-agonists salmeterol and bambuterol.

Design and setting: Pharmacosurveillance cohort study of general practice patients in England.

Patients and participants: 15 406 patients prescribed salmeterol between December 1990 and May 1991, and 8098 patients prescribed bambuterol between February 1993 and December 1995.

Methods: Patients prescribed these drugs by general practitioners in England were identified using the national pharmacovigilance system of prescription event monitoring, in which details of all dispensed prescriptions were provided in confidence by the Prescription Pricing Authority. Questionnaires were sent to the prescriber asking for details of events occurring after the first prescription. In each study an attempt was made to establish the cause of all deaths reported on the questionnaires, via retrieval of the patients’ medical notes or examination of death certificates.

Outcome measures and results: There was little evidence of heterogeneity in the drug-specific death rates and we therefore present the combined age- and gender-specific death rates for the 2 cohorts.Overall, there were 85 asthma deaths among people taking the long-acting β2-agonists studied (bambuterol and salmeterol cohorts combined). The overall death rate was 2.33 [95% confidence interval (CI) 1.84 to 2.84] per 10 000 months of observation. There were 37 asthma deaths among male patients (rate 2.40 per 10 000 months of observation; 95% CI 1.74 to 3.40) and 48 asthma deaths among female patients (rate 3.08 per 10 000 months of observation; 95% CI 2.21 to 3.98). There was no difference in death rates when male and female patients were compared (rate ratio 0.78; 95% CI 0.49 to 1.22; p = 0.26).

Conclusion: Prescription event monitoring is a form of prompted surveillance allowing rapid, uniform, national and practical assessment of newly marketed drugs on large cohorts of patients in England. These data provide benchmark rates from which to assess the performance of newly prescribed anti-asthma drugs and generate hypotheses for later analytical investigation in which confounding by indication and asthma severity can be controlled for. Any differences in these rates should be considered as a source of signal generation within the context of a surveillance programme, rather than as robust evidence of any mortality differential between drugs.

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References

  1. Blauw GJ, Westendorp RGJ. Asthma deaths in New Zealand: whodunnit? Lancet 1995; 345: 2–3

    Article  PubMed  CAS  Google Scholar 

  2. Inman WH, Adelstein AM. Rise and fall of asthma mortality in England and Wales in relation to the use of pressurised aerosols. Lancet 1969; II: 279–85

    Article  Google Scholar 

  3. Jackson RT, Beaglehole R, Rea HH, et al. Mortality from asthma: a new epidemic in New Zealand. BMJ 1982; 285: 771–4

    Article  PubMed  CAS  Google Scholar 

  4. Pearce N, Beasley R, Crane J, et al. End of the New Zealand asthma mortality epidemic. Lancet 1995; 345: 41–4

    Article  PubMed  CAS  Google Scholar 

  5. Crane J, Pearce N, Flatt A, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study. Lancet 1989; I: 917–22

    Article  Google Scholar 

  6. Pearce N, Grainger J, Atkinson M, et al. Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. Thorax 1990; 45: 170–5

    Article  PubMed  CAS  Google Scholar 

  7. Grainger J, Woodman K, Pearce N, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-87. Thorax 1991; 46: 105–11

    Article  PubMed  CAS  Google Scholar 

  8. Spitzer WO, Suissa S, Ernst P, et al. The use of β-agonists and the risk of death and near death from asthma. N Engl J Med 1992; 326: 501–6

    Article  PubMed  CAS  Google Scholar 

  9. Suissa S, Ernst P, Boivin JF, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med 1994; 149: 604–10

    PubMed  CAS  Google Scholar 

  10. Campbell MJ, Cogman GR, Holgate ST, et al. Age specific trends in asthma mortality in England and Wales, 1983-95: results of an observational study. BMJ 1997; 314: 1439–41

    Article  PubMed  CAS  Google Scholar 

  11. Baldwin DR, Ormerod LP, Mackay AD, et al. Change in hospital management of acute severe asthma by general and thoracic physicians in Birmingham and Manchester during 1978 and 1985. Thorax 1990; 45: 130–5

    Article  PubMed  CAS  Google Scholar 

  12. Waller PC, Coulson RA, Wood SM. Regulatory pharmacovigilance in the United Kingdom: current principles and practice. Pharmacoepidemiol Drug Saf 1996; 5: 363–75

    Article  PubMed  CAS  Google Scholar 

  13. Dunn N, Freemantle S, Mann R. Nicorandil and diabetes: examination of an hypothesis generated by prescription-event monitoring. Pharmacoepidemiol Drug Saf 1998; 7Suppl. 2: S100–S1

    Google Scholar 

  14. Martin RM, Dunn NR, Freemantle SN, et al. The risk of nonfatal cardiac failure and ischaemic heart disease with β2-agonists. Thorax 1998; 53: 558–62

    Article  PubMed  CAS  Google Scholar 

  15. Mann RD, Kubota K, Pearce GL, et al. Salmeterol: a study by prescription-event monitoring in a UK cohort of 15,407 patients. J Clin Epidemiol 1996; 49: 247–50

    Article  PubMed  CAS  Google Scholar 

  16. Freemantle SN, Pearce GL, Wilton LV, et al. The incidence of the most commonly reported events with 40 newly marketed drugs: a study by prescription-event monitoring. Pharmacoepidemiol Drug Saf 1997; 6Suppl. 1: S1–S8

    Google Scholar 

  17. Mann RD, Wilton LV, Pearce GL, et al. Prescription-event monitoring in 1996 — a method of non-interventional observational cohort pharmacovigilance. Pharmacoepidemiol Drug Saf 1997; 6Suppl. 3: S5–S11

    Article  PubMed  Google Scholar 

  18. StataCorp. Stata Statistical Software: Release 5.0. College Station, TX: Stata Corporation, 1997

  19. Last JM, editor. A dictionary of epidemiology. 3rd ed. Oxford: Oxford University Press, 1995

    Google Scholar 

  20. Wilton LV, Stephens MDB, Mann RD. Visual field defect associate dwith vigabatrin: observational cohort study.BMJ 1999; 319: 1165–6

    Article  PubMed  CAS  Google Scholar 

  21. Coates JR. Certification of asthma death by general practitioners. Aust Fam Physician 1992; 21(9): 1325–8

    PubMed  CAS  Google Scholar 

  22. Martin RM, Biswas PN, Mann RD. The incidence of adverse events and risk factors for upper gastrointestinal disorders associated with meloxicam use amongst 19,087 patients in general practice in England: cohort study. Br J Clin Pharmacol 2000: 50: 35–42

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to record our keen appreciation of the cooperation of the general practitioners and numerous other colleagues who have helped in this investigation. In addition we wish to thank the Prescription Pricing Authority, the Health Authorities of England and the Office for National Statistics for their important participation. Gilian Pearce managed the prescribing and analytical database. The Drug Safety Research Unit is an independent charity that works in association with the University of Southampton. It receives unconditional donations from pharmaceutical companies. The companies have no control of the conduct or the publication of the studies conducted by the Unit. The Unit has received such funds from GlaxoWellcome and Astra Zeneca.

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Authors and Affiliations

  1. Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, BS8 2PR, England

    Richard M. Martin

  2. Drug Safety Research Unit, Southampton, England

    Saad Shakir

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  1. Richard M. Martin
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  2. Saad Shakir
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Correspondence to Richard M. Martin.

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Martin, R.M., Shakir, S. Age- and Gender-Specific Asthma Death Rates in Patients Taking Long-Acting β2-Agonists. Drug-Safety 24, 475–481 (2001). https://doi.org/10.2165/00002018-200124060-00005

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