How safe are migraine medications for people with cardiovascular disease?

Triptans were associated with fewer major adverse cardiovascular events (MACE) in patients with acute migraine with a history of cardiovascular disease compared to nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids/butalbital, according to registry data patients.

Among those with acute migraine and at least one baseline cardiovascular disease, MACE occurred with 0.90% of triptan prescriptions, 4.52% of opioid/butalbital prescriptions, and 3.76% of NSAID prescriptions, Jessica Ailani, MD, of MedStar Georgetown University Hospital in Washington, DC, reported at the annual meeting of the American Headache Society.

The adjusted hazard ratios for MACE were 0.38 (95% CI 0.22-0.67, P=0.001) comparing triptans to opioids/butalbital and 0.46 (95% CI 0.29-0.71, P

The prescribing information for triptans lists a history of cardiovascular disease as a contraindication, but it’s unclear whether triptans carry higher risks of cardiovascular events than other migraine treatments, Ailani noted.

“Triptans carry a black box warning to avoid their use in known cardiovascular diseases,” Ailani said. MedPage today. “I believe that, even after the results of this summary, this disclaimer is still appropriate..

“Sometimes in practice, migraine patients with cardiovascular disease will be prescribed NSAIDs other than aspirin, opioids, or butalbital without being clear whether these treatments also pose risks,” Ailani pointed out.

“In clinical practice, we have scenarios where a patient has stable cardiovascular disease that is monitored over time, such as well-controlled hypertension or hyperlipidemia,” she added.

Analyzes have shown that more than one in five commercially insured migraine patients have cardiovascular disease that specifically contraindicates treatment with triptans. Another 25% had two or more cardiovascular risk factors identified as triptan warnings and precautions.

In their study, Ailani and colleagues identified adults treated for acute migraine with triptans, NSAIDs other than aspirin, and opioids/butalbital from January 2006 to December 2020 in the Mass General Brigham Research Patient Data Database. Registry. All participants had at least one diagnosis of baseline cardiovascular condition.

MACE was defined as nonfatal stroke, nonfatal MI, facility all-cause mortality, or a composite of the three outcomes. MACE was assessed from the index date until 60 days later, or the date of the change in treatment class, or the end of data availability, whichever comes first.

The index date was defined as the date of each eligible prescription. Multiple prescriptions per patient were included.

Only triptans prescribed as a single anti-migraine treatment were included in the analysis, and combination therapies of opioids/butalbital and NSAIDs other than aspirin were excluded.

The researchers identified 12,121 prescriptions for acute migraine: 4,016 for triptans, 6,084 for opioids/butalbital and 2,021 for NSAIDs. The most frequent index treatments were sumatriptan (Imitrex; 59%) in the triptans cohort, butalbital (38.5%) and oxycodone (27%) in the opioids/butalbital cohort and ibuprofen (61.5 %) in the NSAID cohort.

The mean index ages were 49, 54, and 47 years for the triptans, opioids/butalbital, and NSAIDs cohorts, respectively. Approximately 86% of patients in each group were female.

Compared to the triptan cohort, the opioid/butalbital and NSAID cohorts had higher baseline aspirin use. These cohorts also had a higher likelihood of baseline cardiovascular risk (2.4% for opioids/butalbital, 3.3% for NSAIDs, and 1.6% for triptans). Even after taking this into account, the risk of MACE was still higher for these patients, especially for those who prescribed opioids and butalbital, Ailani noted.

The analysis had several limitations, Ailani acknowledged. Prescription data does not provide information about medication dispensing, compliance, or compliance, which can lead to misclassification of exposure. Only prescription NSAIDs were evaluated, not over-the-counter use.

The study relied on diagnostic codes, which may also have led to misclassification, she added. Residual or unmeasured confusion may have influenced the conclusions, and patients at Mass General Brigham are different from patients in other parts of the country.

“My takeaway is that opioids and butalbital-containing products can pose more risks than just medication overuse headaches and we as prescribers have to be very careful in viewing them as a safe alternative in people at cardiovascular risk,” Ailani observed.

“This study, while having limitations, is a first step to questioning the safety of known treatments in migraine patients with cardiovascular disease,” she said.

  • Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s disease, dementia, MS, rare diseases, epilepsy, autism, headaches , strokes, Parkinson’s disease, ALS, concussions, CTE, sleep, pain, etc. Follow


This analysis was supported by GlaxoSmithKline.

Ailani reported relationships with AbbVie, Amgen, Aeon, Axsome, Biohaven, BioDelivery Scientific International, Eli Lilly, GlaxoSmithKline, Lundbeck, Impel, Neurolief, Neso, Satsuma, Theranica, Teva, Zosano, and Ctrl M.