Drug Safety

, Volume 33, Issue 7, pp 605–613 | Cite as

Fatal and Non-Fatal Cardiovascular Events in a General Population Prescribed Sibutramine in New Zealand

A Prospective Cohort Study
  • Mira Harrison-Woolrych
  • Janelle Ashton
  • Peter Herbison
Original Research Article


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).


  1. 1.
    European Medicines Agency. European Medicines Agency recommends suspension of marketing authorizations for sibutramine. 21 January 2010 [press release; online]. Available from URL: http://www.ema.europa.eu/pdfs/human/referral/sibutramine/3940810en.pdf [Accessed 2010 May 11]
  2. 2.
    US Food and Drug Administration. Meridia (sibutramine hydrochloride): follow-up to an early communication about an ongoing safety review. Available from URL: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm198221.htm [Accessed 2010 May 19]
  3. 3.
    Torp-Pedersen C, Caterson I, Coutinho W, et al. Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial. Eur Heart J 2007; 28: 2915–23PubMedCrossRefGoogle Scholar
  4. 4.
    Thirty-four deaths in sibutramine patients. Scrip 2002; 2730Google Scholar
  5. 5.
    Advisory. Health Canada reports back to public on safety profile of Meridia (sibutramine). Ottawa (ON): Health Canada, 2003 Feb 28 [online]. Available from URL: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2003/2003_07-eng.php [Accessed 2010 May 19]
  6. 6.
    Harrison-Woolrych ML, Coulter DM. PEM in New Zealand. In: Mann R, Andrews EB, editors. Pharmacovigilance. 2nd edition. Chichester: John Wiley and Sons, 2007: 317–32Google Scholar
  7. 7.
    Harrison-Woolrych ML, Clark DWJ, Hill GR, et al. QT interval prolongation associated with sibutramine. Br J Clin Pharmacol 2006; 61(4): 464–9PubMedCrossRefGoogle Scholar
  8. 8.
    Williams G. Withdrawal of sibutramine in Europe. BMJ 2010; 340: c824PubMedCrossRefGoogle Scholar
  9. 9.
    Kunac DL, Harrison-Woolrych ML, Tatley MV. Pharmacovigilance in New Zealand: the role of the New Zealand Pharmacovigilance Centre in facilitating safer medicines use. NZ Med J 2008; 121; 1281: 76–89 [online]. Available from URL: http://www.nzma.org.nz/journal/121-1283/3286 [Accessed 2010 May 11]Google Scholar
  10. 10.
    NZ Ministry of Health. Data and statistics: mortality collection (MORT) [online]. Available from URL: http://www.moh.govt.nz/moh.nsf/indexmh/dataandstatistics-collections-mortality [Accessed 2010 May 11]
  11. 11.
    Hill G, Harrison-Woolrych ML, Ashton J. Sibutramine utilisation in New Zealand: an analysis of prescription data by the Intensive Medicines Monitoring Programme. Pharmacoepidemiol Drug Saf 2007; 16: 1217–26PubMedCrossRefGoogle Scholar
  12. 12.
    Ajani UA, Lotufo PA, Gaziano JM. Body mass index and mortality among US male physicians. Ann Epidemiol 2004; 14: 731–9PubMedCrossRefGoogle Scholar
  13. 13.
    James WP, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Lancet 2000; 356: 2119–25PubMedCrossRefGoogle Scholar
  14. 14.
    Abbott Laboratories (NZ) Ltd. New Zealand datasheet for Reductil [online]. Available from URL: http://www.med-safe.govt.nz/profs/Datasheet/r/Reductilcap.pdf [Accessed 2010 May 19]
  15. 15.
    Russell DG, Wilson NC, Parnell WR, et al. NZ food: NZ people. Key results of the 1997 National Nutrition Survey. Wellington: Ministry of Health, 1999 [online]. Available from URL: http://www.moh.govt.nz/moh.nsf/pagesmh/852 [Accessed 2010 May 11]Google Scholar
  16. 16.
    Calle EE, Thun MJ, Petrelli JM, et al. Body mass index and mortality in a prospective cohort study of US adults. N Engl J Med 1999; 341(15): 1097–105PubMedCrossRefGoogle Scholar
  17. 17.
    Ernest D, Gershenzon A, Corallo CE, et al. Sibutramine-associated QT interval prolongation and cardiac arrest. Ann Pharmacother 2008; 42: 1514–7PubMedCrossRefGoogle Scholar
  18. 18.
    Eroglu E, Gemici G, Bayrak F, et al. Acute myocardial infarction in a 24 year-old man possibly associated with sibutramine use. Int J Cardiol 2009; 137: e43–5PubMedCrossRefGoogle Scholar
  19. 19.
    von Haehling S, Lainscak M, Anker SD. Sibutramine in cardiovascular disease: is SCOUT the new STORM on the horizon? Eur Heart J 2007; 28: 2830–1CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Mira Harrison-Woolrych
    • 1
  • Janelle Ashton
    • 1
  • Peter Herbison
    • 1
  1. 1.Intensive Medicines Monitoring Programme, Department of Preventive and Social MedicineUniversity of OtagoDunedinNew Zealand

Personalised recommendations