How Safe Are Migraine Drugs for People With Cardiovascular Conditions?

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

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

Adjusted hazard ratios for MACE were 0.38 (95% CI 0.22-0.67, P=0.001) comparing triptans with opioids/butalbital and 0.46 (95% CI 0.29-0.71, P<0.001) comparing triptans with NSAIDs.

Prescribing information for triptans list history of cardiovascular disease as a contraindication, but it’s not clear whether triptans pose greater risks of cardiovascular events than other migraine therapies, Ailani noted.

“Triptans carry a black box warning to avoid use in known cardiovascular disease,” Ailani told MedPage Today. “I believe, even after the results of this abstract, this warning is still appropriate.“

“Sometimes in practice, migraine patients with cardiovascular disease will be prescribed non-aspirin NSAIDs or opioids or butalbital without a clear understanding of whether these treatments present risks as well,” Ailani pointed out.

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

Analyses have shown that more than one in five commercially insured migraine patients had a cardiovascular condition that specifically contraindicated triptan treatment. An additional 25% had two or more cardiovascular risk factors identified as warnings and precautions to triptans.

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

MACE was defined as nonfatal stroke, nonfatal MI, in-facility all-cause mortality, or a composite of the three outcomes. MACE was assessed from the index date to 60 days later, or the date of treatment class switch, or the end of data availability, whichever came 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 non-aspirin NSAIDs 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 triptan cohort, butalbital (38.5%) and oxycodone (27%) in the opioid/butalbital cohort, and ibuprofen (61.5%) in the NSAID cohort.

Mean ages at index were 49, 54, and 47 for the triptan, opioid/butalbital, and NSAID cohorts, respectively. About 86% of patients in each group were women.

Compared with the triptan cohort, the opioid/butalbital and NSAID cohorts had higher baseline usage of aspirin. These cohorts also had higher probability of baseline cardiovascular risk (2.4% for opioids/butalbital, 3.3% for NSAIDs, and 1.6% for triptans). Even after accounting for this, the risk of MACE was still higher for these patients, especially for those prescribed opioids and butalbital, Ailani noted.

The analysis had several limitations, Ailani acknowledged. Prescription data do not provide information on drug dispensing, adherence, or compliance, and this may lead to exposure misclassification. Only prescription NSAIDs were assessed, not over-the-counter use.

The study relied on diagnosis codes, which may have led to misclassification as well, she added. Residual or unmeasured confounding may have influenced 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 may have more risk to them than just medication overuse headache and we, as prescribers, should be very careful in considering them a safe alternative in those with cardiovascular risk,” Ailani observed.

“This study, while having limitations, is a first step to question how safe are known treatments in migraine patients with cardiovascular disease,” she said.