Dihydroergotamine Safe in Chronic Migraine With Cardiovascular Risk

Stephen Silberstein, MD

Data from a single-center, retrospective cohort study published in Headache reported no significant cardiovascular adverse events (AEs) or EKG change among patients with a higher risk of ischemic events who were treated with dihydroergotamine (DHE) for their chronic migraine condition. All told, patients achieved significant rates of pain freedom and reduction; however, more prospective studies assessing the long-term effects of DHE in patients with elevated cardiovascular risk is needed, the study authors wrote.¹

The trial, conducted at the Jefferson Headache Center at Thomas Jefferson University, featured 347 inpatients with chronic migraine who were treated with intravenous DHE protocol between January and October 2019. In total, 227 (81.1%) of these had atherosclerotic cardiovascular disease (ASCVD) 10-year calculated risk scores, with 64 (28.2%) having elevated risk and 38 (16.7%) having cardiology consultations. Investigators used the 11-point daily pain numeric rating scale (NRS) as the primary outcome assessment to judge treatment effectiveness of DHE.

Led by senior author Stephen Silberstein, MD, director of the Jefferson Headache Center, patients had medications adjusted daily based on reported pain intensity and AEs. For analyses, the single values of the NRS from the time of admission and the time of discharge were used. DHE was uptitrated to maximally tolerable or 1 mg every 8 h. Cardiovascular risk factors included in the study were sex, age, race, total and high-density lipoprotein cholesterol levels, systolic blood pressure, treatment for elevated blood pressure, diabetes, and smoking history.

Most of the patient cohort who had calculable ASCVD risk scores were female (81.1%) and White (89.9%). In those with elevated ASCVD, 29.7% had borderline risk, 56.3% had intermediate risk, and 14.1% had high risk. Most patients tolerated the maximum dose of 1 mg per administration of DHE (55.6%); however, in comparison with the low-ASCVD risk group, fewer patients with elevated risk received the max dose (42.2% vs 64.4%; P = .002) and lower median doses of DHE on discharge (0.75 [0.5-1] mg vs 1 [0.75-1] mg; P <.001).

Among the total 347-patient cohort, no patients experienced clinically meaningful cardiovascular AEs. Between the low- and elevated-risk groups, there were no differences in the most common abnormal EKG readings. Patients in these groups also had similar rates of AEs such as nausea, chest pain, NSVT, DVTs, and visual symptoms. Elevated-risk patients had higher mean arterial blood pressure (MAP) on admission, at maximum, and at discharge than the low-risk patients and higher use of antihypertensive medications (42.2% vs 13.5%; P <.001).

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In terms of efficacy, treated patients showed a within-group reduction of –4 (25th percentile, 3; 75th percentile, 6; P <.001) in overall median pain intensity. Of the entire cohort, 157 patients (45.2%) achieved headache freedom, otherwise NRS scores of 0, at discharge. Although both the low- and elevated-ASCVD groups had similar pain intensities at admission and discharge, significant pain reduction was more pronounced in the low-ASCVD group (–5.0 [3-7] vs –3.8 [2.1-6]; P = .037).

Study authors claimed this was the first such study to report specifically on cardiovascular AEs associated with intravenous DHE use in patients at a higher risk of ischemic events. The study had several limitations, including the fact that it was single-centered and there was no placebo arm or control.

Study authors also noted that, "The high degree of pre-existing disability in this population may necessitate more aggressive pharmacologic treatments in exchange for the risks of polypharmacy, compared to a less disabled population. The JHC headache protocol is administered and uptitrated via provider discretion in discussion with patients. Patients with apparent, significant cardiovascular risk usually do not receive DHE. The true DHE risk in patients with major cardiovascular risk is thus not examined in this study."

REFERENCE
1. Wang VS, Kosman J, Yuan H, et al. Safety, tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractor chronic migraine with cardiovascular risk factors: a retrospective study. Headache. 2023;63(9):1251-1258. doi:10.1111/head.14636