Age- and gender-specific asthma death rates in patients taking long-acting β2-Agonists -: Prescription event monitoring pharmacosurveillance studies

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 beta (2)-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 clients 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 beta (2)-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 inter 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 contest of a surveillance programme. rather than as robust evidence of any mortality differential between drugs.