Yang Seonkyeong, Orlova Yulia, Park Haesuk, Smith Steven M, Guo Yi, Chapin Benjamin A, Wilson Debbie L, Lo-Ciganic Wei-Hsuan
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville.
Mayo Clinic, Jacksonville, Florida.
JAMA Neurol. 2025 Feb 1;82(2):132-141. doi: 10.1001/jamaneurol.2024.4537.
Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP mAbs) offer effective migraine-specific preventive treatment. However, concerns exist about their potential cardiovascular risks due to CGRP blockade.
To compare the incidence of cardiovascular disease (CVD) between Medicare beneficiaries with migraine who initiated anti-CGRP-mAbs vs onabotulinumtoxinA in the US.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective, sequential cohort study was conducted among a nationally representative population-based sample of Medicare claims from May 2018 through December 2020. Data analysis was performed from August to December 2023. This study included fee-for-service Medicare beneficiaries aged 18 years or older with migraine who initiated either anti-CGRP mAbs or onabotulinumtoxinA. Beneficiaries who had a history of myocardial infarction (MI), stroke, cluster headache, malignant cancer, or hospice service within a 1-year baseline period prior to treatment initiation were excluded. To minimize channeling bias from new drug introductions and time-related bias due to the COVID-19 pandemic, 5 cohorts were established, representing sequential 6-month calendar intervals based on the initial prescription or date of index anti-CGRP mAbs or onabotulinumtoxinA use.
Anti-CGRP mAbs vs onabotulinumtoxinA.
The primary outcome was time to first MI or stroke. Secondary outcomes included hypertensive crisis, peripheral revascularization, and Raynaud phenomenon. The inverse probability of treatment-weighted Cox proportional hazards models were used to compare outcomes between the 2 treatment groups.
Among 266 848 eligible patients with migraine, 5153 patients initiated anti-CGRP mAbs (mean [SD] age, 57.8 [14.0] years; 4308 female patients [83.6%]) and 4000 patients initiated onabotulinumtoxinA (mean [SD] age, 61.9 [13.7] years; 3353 female patients [83.8%]). Use of anti-CGRP mAbs was not associated with an increased risk of composite CVD events (adjusted hazard ratio [aHR], 0.88; 95% CI, 0.44-1.77), hypertensive crisis (aHR, 0.46; 95% CI, 0.14-1.55), peripheral revascularization (aHR, 1.50; 95% CI, 0.48-4.73), or Raynaud phenomenon (aHR, 0.75; 95% CI, 0.45-1.24) compared with onabotulinumtoxinA. Subgroup analyses by age group and presence of established non-MI or stroke CVD showed similar findings.
In this cohort study, despite initial concerns regarding the cardiovascular effects of CGRP blockade, anti-CGRP mAbs were not associated with an increased risk of CVD compared with onabotulinumtoxinA among adult Medicare beneficiaries with migraine, who were predominantly older adults or individuals with disability. Future studies with longer follow-up periods and in other populations are needed to confirm these findings.
靶向降钙素基因相关肽（CGRP）或其受体的单克隆抗体（mAbs，抗CGRP mAbs）为偏头痛提供了有效的特异性预防性治疗。然而，由于CGRP阻断，人们对其潜在的心血管风险存在担忧。
比较美国开始使用抗CGRP mAbs与肉毒杆菌毒素A（onabotulinumtoxinA）的偏头痛医疗保险受益人心血管疾病（CVD）的发病率。
设计、设置和参与者：这项回顾性、序贯队列研究是在2018年5月至2020年12月全国代表性的基于人群的医疗保险索赔样本中进行的。数据分析于2023年8月至12月进行。本研究纳入了年龄在18岁及以上、开始使用抗CGRP mAbs或肉毒杆菌毒素A的偏头痛按服务收费医疗保险受益人。在开始治疗前1年基线期内有心肌梗死（MI）、中风、丛集性头痛、恶性肿瘤或临终关怀服务史的受益人被排除。为了尽量减少新药引入导致的渠道偏差和由于2019冠状病毒病大流行造成的时间相关偏差，建立了5个队列，根据初始处方或首次使用抗CGRP mAbs或肉毒杆菌毒素A的日期，代表连续6个月的日历间隔。
抗CGRP mAbs与肉毒杆菌毒素A。
主要结局是首次发生MI或中风的时间。次要结局包括高血压危象、外周血管重建和雷诺现象。使用治疗加权Cox比例风险模型的逆概率来比较两个治疗组的结局。
在266848例符合条件的偏头痛患者中，5153例患者开始使用抗CGRP mAbs（平均[标准差]年龄，57.8[14.0]岁；4308例女性患者[83.6%]），4000例患者开始使用肉毒杆菌毒素A（平均[标准差]年龄，61.9[13.7]岁；3353例女性患者[83.8%]）。与肉毒杆菌毒素A相比，使用抗CGRP mAbs与复合CVD事件风险增加无关（调整后风险比[aHR]，0.88；95%置信区间，0.44 - 1.77）、高血压危象（aHR，0.46；95%置信区间，0.14 - 1.55）、外周血管重建（aHR，1.50；95%置信区间，0.48 - 4.73）或雷诺现象（aHR，0.75；95%置信区间，0.45 - 1.24）。按年龄组和已确诊的非MI或中风CVD进行的亚组分析显示了类似的结果。
在这项队列研究中，尽管最初担心CGRP阻断的心血管效应，但在主要为老年人或残疾个体的成年偏头痛医疗保险受益人中，与肉毒杆菌毒素A相比，抗CGRP mAbs与CVD风险增加无关。需要进行更长随访期和在其他人群中的进一步研究来证实这些发现。
