Supplementing Systematic Review Evidence with Health System Data: A Target Trial Emulation of Triptan in Migraine Patients with Increased Cardiovascular Risk
2Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA
Background: A recent framework from the US Evidence-based Practice Centers advises that when evidence from systematic reviews is deemed insufficient for decision-making, electronic health record (EHR) data from health systems should be considered to fill the knowledge gap. A 2021 systematic review demonstrated that triptans improved pain and function for acute migraine attacks. However, the systematic review identified insufficient evidence about patients with increased risk of cardiovascular events who were often excluded from clinical trials.
Objectives: To evaluate the safety of triptan treatments in migraine patients with cardiovascular disease or multiple cardiovascular risk factors using EHR data from a large tri-state health system.
Methods: This target trial emulated a randomized clinical trial that hypothetically assigned patients to triptans or no triptan treatments. Eligible patients were adults (aged ≥18 years) with at least a 1-year history of migraines, confirmed cardiovascular or cerebrovascular disease, or with at least two cardiovascular risk factors. Patients in the triptan group were matched with those in the no-triptan group in a 1:1 ratio. The primary outcome was major adverse cardiovascular events (MACE) at 60 days of starting treatments.
Results: A total of 3,719 patients who received triptan were matched to 3,719 patients who did not receive triptans (Table 1). Figure 1 shows the cumulative incidence curves for MACE. The absolute risk of MACE outcomes was low (Table 2). At 60 days, 154 patients (4.14%) in the triptan group reported a MACE outcome compared to 37 patients (0.99%) in the no triptan group (RR: 4.16; 95% CI: 2.96 – 5.84). Patients treated with triptans also had significantly higher risk of nonfatal myocardial infarction, nonfatal stroke, transient cerebral ischemia, and heart failure. Five patients (0.13%) in the triptan group died versus seven (0.19%) in the non-triptan group. Certainty in the evidence was judged to be moderate.
Conclusions: This target trial emulation showed that triptans were associated with increased risk of MACE outcomes, raising the certainty of evidence in this outcome from insufficient, as was judged in a systematic review, to moderate. Patient, public, and/or healthcare consumer involvement: None.