Fatal and Non-Fatal Cardiovascular Events in a General Population Prescribed Sibutramine in New Zealand
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Background: The cardiovascular safety of sibutramine is currently under review by medicines regulatory authorities worldwide after the SCOUT (Sibutramine Cardiovascular Outcome Trial) showed an increased risk of cardiovascular events in patients taking sibutramine. Further data regarding the cardiovascular safety of sibutramine in a general population are now required.
Objective: To quantify the risk of fatal and non-fatal cardiovascular adverse events in a general population prescribed sibutramine in postmarketing use.
Study Design: Observational prospective cohort study of patients dispensed sibutramine during a 3-year period (2001–4) and followed up for at least 1 year after their last prescription. The study included record-linkage to national mortality datasets to identify fatal events.
Setting: Postmarketing ‘real-life’ use of sibutramine in a general population in New Zealand.
Patients: All New Zealand patients dispensed a prescription for sibutramine in a 3-year period (for whom a National Health Identification number could be validated). 15 686 patients were included in the record linkage study for fatal events. A subgroup of 9471 patients was followed up by intensive methods for non-fatal events.
Main Outcome Measures: (i) Rate of death from all causes and from cardiovascular events; and (ii) rates of non-fatal cardiovascular adverse events.
Results: Total exposure to sibutramine for 15 686 patients in the validated cohort was 5431 treatment-years. The rate of death from all causes in this cohort was 0.13 (95% CI 0.05, 0.27) per 100 treatment-years exposure. The rate of death from a cardiovascular event was 0.07 (95% CI 0.02,0.19) per 100 treatment-years exposure. The most frequent non-fatal cardiovascular events in the intensively followed up cohort were hypertension, palpitations, hypotensive events and tachycardia.
Conclusions: Risk of death from a cardiovascular event in this general population of patients prescribed sibutramine was lower than has been reported in other overweight/obese populations. The results of this study suggest that further evaluation of the benefit-risk profile of sibutramine is now required.
During the time this study was conducted, the IMMP received funding from Medsafe, the medicines regulatory authority at the New Zealand Ministry of Health. Unconditional donations/grants have also been received from pharmaceutical companies, including Abbott Laboratories who are the New Zealand sponsor for sibutramine (Reductil®) and who provided an unconditional donation to the IMMP during the 3 years of data collection for this study.
None of the funding sources have had a role in the design, conduct, analysis or interpretation of the results of this study, nor have they been involved in the writing of this report.
None of the authors have any conflicts of interest to declare. All authors had full access to all of the data in the study and we take responsibility for the integrity of the data and the accuracy of the data analysis.
We are very grateful to Elizabeth Watson at the IMMP for her help in data preparation. We also thank Jim Slattery, biostatistician, for his input to this work and for reviewing early drafts of the manuscript.
The IMMP is a long-standing national medicines surveillance programme and its processes and practices have been approved by the New Zealand Privacy Commissioner. This study was carried out under the existing and ongoing IMMP ethical approval granted by the Otago Ethics Committee (reference OTA/04/32/CPD).
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