European Journal of Clinical Pharmacology

, Volume 63, Issue 8, pp 801–807 | Cite as

Triptan use and risk of cardiovascular events: a nested-case-control study from the French health system database

  • S. Lugardon
  • H. Roussel
  • V. Sciortino
  • J. L. Montastruc
  • M. Lapeyre-Mestre
Pharmacoepidemiology and Prescription

Abstract

Background

The use of triptans (5-HT agonists) in the treatment of migraine is associated with a potential increasing risk of cardiovascular events and raises the question of the relationship between overuse and the occurrence of ischemic events.

Objective

The aim of this study was to examine the association between the intensity of triptan use and occurrence of an cardiac event.

Methods

Using the reimbursed drug prescription database of the National French Health Insurance System in the Midi-Pyrenees area, we identified subjects receiving at least one triptan in the second semester of 2002. From this population, we selected new users and retrieved all reimbursed care data up to 31 December 2003. We estimated the patterns of triptan exposure by calculating the number of defined daily doses (DDD) received per 30-day period. Another reimbursed health care database was used to identify as cases of cardiac outcomes those patients receiving care for the management of a possible heart ischemic event. Each case was randomly matched on age and gender with four controls free of any cardiovascular event before the index date. A conditional logistic regression was performed to assess the relationship between cardiac outcomes and exposure to triptans in the 30 days before the index date.

Results

The cohort of new users of triptans included 8625 subjects, 4414 (51.18%) of whom received only one dispensation for triptans during the follow-up period (median duration: 427 days). For the remaining subjects, the peak of triptans delivery was ≤8 DDD for 14.68% of the cohort, between 9 and 14 DDD for 22.17%, between 15 and 29 for 10.04% and ≥30 DDD for 1.92%. Fifty-seven users (0.66%) presented a cardiac history and 1388 patients (16.09%) had cardiovascular risk factors. We identified 155 incident cases of cardiac outcomes during the follow-up and compared these to 620 matched controls. Cases were older and presented more frequently with cardiac history or cardiovascular risk factors than the other users of triptans. The distribution exposure to triptans did not significantly differ between cases and controls with an odds ratio for an exposure ≤8 DDD in the last 30 days of 0.74 [95% CI (0.31–1.77)] and that for an exposure >8 DDD equal to 1.14 [95% CI (0.58–2.27)].

Conclusion

The proportion of patients showing an overuse of triptans (more than 15 DDD for 30 days) reached 12% in this cohort of new users of triptans. However, we did not find any relationship between the overuse of triptans and cardiac outcomes. This study also shows that some patients with cardiovascular risk factors are actually treated by triptans. These patients are more likely to present a cardiac outcome potentially related to an ischemic event after the introduction of triptan.

Keywords

Cardiovascular events Ischemic event Overuse Triptans 

References

  1. 1.
    Henry P, Auray JP, Gaudin AF, Dartigues JF, Duru G, Lanteri-Minet M, Lucas C, Pradalier A, Chazot G, El Hasnaoui A (2002) Prevalence and clinical characteristics of migraine in France. Neurology 59(2):232–237PubMedGoogle Scholar
  2. 2.
    Henry P, Michel P, Brochet B, Dartigues JF, Tison S, Salamon R (1992) A nationwide survey of migraine in France: prevalence and clinical features in adults. GRIM. Cephalalgia 12(4):229–237PubMedCrossRefGoogle Scholar
  3. 3.
    Mitchell P, Wang JJ, Currie J, Cumming RG, Smith W (1998) Prevalence and vascular associations with migraine in older Australians. Aust N Z J Med 28(5):627–632PubMedGoogle Scholar
  4. 4.
    Jamieson DG (2002) The safety of triptans in the treatment of patients with migraine. Am J Med 112(2):135–140PubMedCrossRefGoogle Scholar
  5. 5.
    Ottervanger JP, Paalman HJ, Boxma GL, Stricker BH (1993) Transmural myocardial infarction with sumatriptan. Lancet 341(8849):861–862PubMedCrossRefGoogle Scholar
  6. 6.
    Laine K, Raasakka T, Mantynen J, Saukko P (1999) Fatal cardiac arrhythmia after oral sumatriptan. Headache 39(7):511–512PubMedCrossRefGoogle Scholar
  7. 7.
    Mueller L, Gallagher RM, Ciervo CA (1996) Vasospasm-induced myocardial infarction with sumatriptan. Headache 36(5):329–331PubMedCrossRefGoogle Scholar
  8. 8.
    Souyri C, Lacroix I, Pathak A, Montastruc JL (2005) Coronary adverse reactions to triptans: an analysis of the French pharmacovigilance database. Fund Clin Pharmacol 19:228, (Abstract)Google Scholar
  9. 9.
    Roussel H, Lo Re G, Honorat C, Alonso M, Sciortino V (2006) The use of triptan in ambulatory medicine in Midi-Pyrenees region: clinical and pharmacological contra-indications and drug abuse. Therapie 61(6):507–516PubMedCrossRefGoogle Scholar
  10. 10.
    Gaits D, Hallas J, Sindrup SH, Gram LF (1996) Is overuse of sumatriptan a problem? A population-based study. Eur J Clin Pharmacol 50(3):161–165CrossRefGoogle Scholar
  11. 11.
    Zwart JA, Dyb G, Hagen K, Svebak S, Stovner LJ, Holmen J (2004) Analgesic overuse among subjects with headache, neck, and low-back pain. Neurology 62(9):1540–1544PubMedGoogle Scholar
  12. 12.
    Gaist D (1999) Use and overuse of sumatriptan. Pharmacoepidemiological studies based on prescription register and interview data. Cephalalgia 19(8):735–761PubMedCrossRefGoogle Scholar
  13. 13.
    Silberstein SD, Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ, Gobel H, Lainez MJ, Lance JW, Lipton RB, Nappi G, Sakai F, Schoenen J, Steiner TJ; International Headache Society (2005) The International Classification of Headache Disorders, 2nd edition (ICHD-II)-revision of criteria for 8.2 medication-overuse headache. Cephalalgia 25:460–465PubMedCrossRefGoogle Scholar
  14. 14.
    Geraud G, Lanteri-Minet M, Lucas C, Valade D; French Society for the Study of Migraine Headache (SFEMC) (2004) French guidelines for the diagnosis and management of migraine in adults and children. Clin Ther 26:1305–1318PubMedCrossRefGoogle Scholar
  15. 15.
    Lucas C, Auray JP, Gaudin AF, Dartigues JF, Duru G, Henry P, Lanteri-Minet M, Pradalier A, Chazot G, El Hasnaoui A (2004) Use and misuse of triptans in France: data from the GRIM2000 population survey. Cephalalgia 24(3):197–205PubMedCrossRefGoogle Scholar
  16. 16.
    Tepper S, Allen C, Sanders D, Greene A, Boccuzzi S (2003) Coprescription of triptans with potentially interacting medications: a cohort study involving 240,268 patients. Headache 43:44–48PubMedCrossRefGoogle Scholar
  17. 17.
    Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC (2003) Single use of sumatriptan: a patient interview study. Headache 43(2):109–116PubMedCrossRefGoogle Scholar
  18. 18.
    Senard JM, Nachit-Ouinekh F, Becq JP, Chastan G, Fabre N, El Hasnaoui A (2004) Triptan use in general practice: a French pharmacoepidemiological study. Therapie 59(5):533–539PubMedCrossRefGoogle Scholar
  19. 19.
    Velentgas P, Cole JA, Mo J, Sikes CR, Walker AM (2004) Severe vascular events in migraine patients. Headache 44(7):642–651PubMedCrossRefGoogle Scholar
  20. 20.
    Hall GC, Brown MM, Mo J, MacRae KD (2004) Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice. Neurology 62(4):563–568PubMedGoogle Scholar
  21. 21.
    Wammes-van der Heijden EA, Rahimtoola H, Leufkens HGM, Tijssen CC, Egberts ACG (2006) Risk of ischemic complications related to the intensity of triptan and ergotamine use. Neurology 67(7):1128–1134PubMedCrossRefGoogle Scholar
  22. 22.
    Arveiler D, Wagner A, Ducimetière P, Montaye M, Ruidavets JB, Bingham A, Ferrieres J, Amouyel P, Haas B (2005) Trends in coronary heart disease in France during the second half of the 1990s. Eur J Cardiovasc Prev Rehabil 12(3):209–215PubMedCrossRefGoogle Scholar
  23. 23.
    Moride Y, Abenhaim L (1994) Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research. J Clin Epidemiol 47(7):731–737PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • S. Lugardon
    • 1
  • H. Roussel
    • 2
  • V. Sciortino
    • 2
  • J. L. Montastruc
    • 1
  • M. Lapeyre-Mestre
    • 1
  1. 1.Unité de Pharmacoépidémiologie, EA 3696, Service de Pharmacologie Clinique, Faculté de MédecineUniversité Paul SabatierToulouseFrance
  2. 2.Direction Régionale du Service Médical de Midi-PyrénéesCNAMTSToulouseFrance

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