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


CONCLUSIONS
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.
Lugardon
S
S
Unité de Pharmacoépidémiologie, EA 3696, Service de Pharmacologie Clinique, Faculté de Médecine, Université Paul Sabatier, 37 allées Jules-Guesde, 31000, Toulouse, France, lapeyre@cict.fr.
Roussel
H
H
Sciortino
V
V
Montastruc
J L
JL
Lapeyre-Mestre
M
M
D000328:Adult; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy; D012306:Risk; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D014363:Tryptamines / Q000009:adverse effects* / Q000627:therapeutic use
D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines