A recently published study of more than 25,000 patients with migraine showed that cardiovascular events (CV) occurred slightly more in patients on triptans than not; however, a multivariable analysis revealed no significant association between triptan use and increased CV events. Overall, this study reinforced the safety of triptans to treat migraine, and further highlighted the importance of considering individual risk factors when prescribing triptans.1
Published in Migraine, the retrospective study conducted in southern Israel analyzed electronic medical records from January 2000 to 2022 for 26,054 patients with migraine, 12,560 (48.2%) of whom initiated triptan therapy. At baseline, the prevalence of CV risk factors including dyslipidemia, diabetes mellitus, hypertension, smoking, atrial fibrillation, and obesity were higher in the non-triptan group (standardized mean difference [SMD] = 0.028-0.289).
When comparing the groups, the prevalence of CV events, including myocardial infarction and ischemic stroke, was slightly higher in the triptan group (5.1%) compared with the non-triptan group (4.1%; SMD = 0.047). Of note, medication usage, including acetylsalicylic acid, anticoagulants, antiplatelets, statins, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, was also higher in the non-triptan group coming into the study (SMD = 0.023-0.105).
“Triptans remain contraindicated in patients with prior myocardial infarction, stroke, or uncontrolled hypertension, and our study does not suggest that triptans are safe in those specific populations,” lead author Ido Peles, MD, PhD, team lead of Medical Data Analysis at the Soroka Medical Center, Ben-Gurion University of the Negev, and colleagues, wrote. “The distinction between contraindications and general CV risk factors is critical, as overestimating risk could lead to unnecessary avoidance of triptans in patients who might otherwise benefit from effective migraine treatment.”
A small subset of patients in the triptan group, 0.3% (n = 33), experienced a subsequent CV event within 90 days from triptans; however, this group had a higher prevalence of CV risk factors (SMD = 2.624). Additionally, patients with migraine with subsequent CV events were more likely to have used triptans more frequently, with 81.8% using triptans more than once compared with 51.0% in the non-CV group (SMD = 1.366). In addition, the mean number of triptan pills per month was significantly higher in the CV event group (2.8 vs 1.9 pills/month; SMD = 0.328).
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In terms of triptan usage patterns, the mean age at initiation was 40.5 (SD, 14.2) years, with most patients (89.5%) using 1-4 pills/month. Sumatriptan, found in 36.3% of triptan-treated patients, was the most common, followed by rizatriptan (30.4%) and eletriptan (28.2%). A small portion of patients (14.0%) used 5-9 pills/month, and an even smaller portion (9.2%) used at least 10 pills, indicative of medication overuse.
An exposure-outcome association analysis using a multivariable weighted mixed-effects survival regression model adjusted for demographic variables and CV risk factors, such as hypertension, diabetes, smoking, dyslipidemia, and obesity. All told, results revealed that the use of triptans in the 3 months prior to the CV event was not significantly associated with an increased hazard for these events (adjusted HR [aHR], 0.96; 95% CI, 0.77-1.23).
Several different sensitivity analyses showed that (A) both 1 month (aHR, 0.84; 95% CI, 0.68-1.06) and 6 months (aHR, 0.83; 95% CI, 0.67-1.05) post-triptan purchase and (B) whether the patients took triptans only once (aHR, 0.99; 95% CI, 0.69-1.15) or more than once (aHR, 1.02; 95% CI, 0.83-1.29) had no significant risk on CV events. Similarly, specific type of triptan (aHR, 0.79-1.07) and the monthly mean number of triptans taken had no statistically significant risk of CV events, further reinforcing the primary findings.
“These findings may provide reassurance to clinicians and ease concerns regarding the CV safety of triptans for patients with CV risk factors, where no formal contraindication exists,” Peles et al concluded. “Nevertheless, it is essential for clinicians to carefully evaluate individualized patient profiles when prescribing triptans to patients with migraine, including monitoring of high-frequency users, particularly for patients with underlying or emerging CV risks.”