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.
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References
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):232–237
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):229–237
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):627–632
Jamieson DG (2002) The safety of triptans in the treatment of patients with migraine. Am J Med 112(2):135–140
Ottervanger JP, Paalman HJ, Boxma GL, Stricker BH (1993) Transmural myocardial infarction with sumatriptan. Lancet 341(8849):861–862
Laine K, Raasakka T, Mantynen J, Saukko P (1999) Fatal cardiac arrhythmia after oral sumatriptan. Headache 39(7):511–512
Mueller L, Gallagher RM, Ciervo CA (1996) Vasospasm-induced myocardial infarction with sumatriptan. Headache 36(5):329–331
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)
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):507–516
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):161–165
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):1540–1544
Gaist D (1999) Use and overuse of sumatriptan. Pharmacoepidemiological studies based on prescription register and interview data. Cephalalgia 19(8):735–761
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 25:460–465
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 26:1305–1318
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):197–205
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 43:44–48
Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC (2003) Single use of sumatriptan: a patient interview study. Headache 43(2):109–116
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):533–539
Velentgas P, Cole JA, Mo J, Sikes CR, Walker AM (2004) Severe vascular events in migraine patients. Headache 44(7):642–651
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):563–568
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):1128–1134
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):209–215
Moride Y, Abenhaim L (1994) Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research. J Clin Epidemiol 47(7):731–737
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Lugardon, S., Roussel, H., Sciortino, V. et al. Triptan use and risk of cardiovascular events: a nested-case-control study from the French health system database. Eur J Clin Pharmacol 63, 801–807 (2007). https://doi.org/10.1007/s00228-007-0332-2
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DOI: https://doi.org/10.1007/s00228-007-0332-2