BackgroundIn addition to the increased risk for cardiovascular (CV) disease and CV events associated with migraine, patients with migraine can also present with a number of CV risk factors (CVRFs). Existing treatment options can be limited due to contraindications, increased burden associated with monitoring, or patient avoidance of side effects. Safe and effective migraine treatment options are needed for patients with migraine and a history of CV or cerebrovascular disease or with increased risk for CV events. This analysis was designed to evaluate the safety and efficacy of oral lasmiditan, a selective serotonin 5-hydroxytryptamine 1F receptor agonist, in acute treatment of migraine attacks in patients with CVRFs.MethodsSAMURAI and SPARTAN were similarly designed, Phase 3, randomized, double-blind, placebo-controlled trials in adults treating a single migraine attack with lasmiditan 50, 100, or 200 mg. Both studies included patients with CVRFs, and SPARTAN allowed patients with coronary artery disease, clinically significant arrhythmia, or uncontrolled hypertension. Efficacy and safety of lasmiditan in subgroups of patients with differing levels of CVRFs are reported. For efficacy analyses, logistic regression was used to assess treatment-by-subgroup interactions. For safety analyses, Cochran-Mantel-Haenszel test of general association evaluated treatment comparisons; Mantel-Haenszel odds ratio assessed significant treatment effects.ResultsIn this pooled analysis, a total of 4439 patients received ≥1 dose of study drug. A total of 3500 patients (78.8%) had ≥1 CVRF, and 1833 patients (41.3%) had ≥2 CVRFs at baseline. Both trials met the primary endpoints of headache pain freedom and most bothersome symptom freedom at 2 h. The presence of CVRFs did not affect efficacy results. There was a low frequency of likely CV treatment-emergent adverse events (TEAEs) overall (lasmiditan, 30 [0.9%]; placebo, 5 [0.4%]). There was no statistical difference in the frequency of likely CV TEAEs in either the absence or presence of any CVRFs. The only likely CV TEAE seen across patients with ≥1, ≥ 2, ≥ 3, or ≥ 4 CVRFs was palpitations.ConclusionsWhen analyzed by the presence of CVRFs, there was no statistical difference in lasmiditan efficacy or the frequency of likely CV TEAEs. Despite the analysis being limited by a single-migraine-attack design, the lack of differences in efficacy and safety with increasing numbers of CVRFs indicates that lasmiditan might be considered in the treatment algorithm for patients with CVRFs. Future studies are needed to assess long-term efficacy and safety.Trial registrationClinicalTrials.govNCT02439320 (SAMURAI), registered 18 March 2015 and ClinicalTrials.govNCT02605174 (SPARTAN), registered 11 November 2015.

中文翻译：

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Lasmiditan 用于急性治疗有心血管危险因素的偏头痛患者：对 2 项随机、双盲、安慰剂对照 3 期试验汇总结果进行事后分析


背景除了与偏头痛相关的心血管 (CV) 疾病和 CV 事件风险增加之外，偏头痛患者还可能存在许多 CV 危险因素 (CVRF)。由于禁忌症、监测相关负担增加或患者避免副作用，现有的治疗选择可能受到限制。对于患有偏头痛且有心血管或脑血管疾病史或心血管事件风险增加的患者，需要安全有效的偏头痛治疗方案。该分析旨在评估口服 lasmiditan（一种选择性血清素 5-羟色胺 1F 受体激动剂）在急性治疗 CVRF 患者偏头痛发作中的安全性和有效性。方法SAMURAI 和 SPARTAN 的设计类似，3 期、随机、双盲，在成人中使用 lasmiditan 50、100 或 200 mg 治疗单次偏头痛发作的安慰剂对照试验。这两项研究均纳入了患有 CVRF 的患者，而 SPARTAN 则允许患有冠状动脉疾病、有临床意义的心律失常或未受控制的高血压的患者进行研究。报道了 lasmiditan 在不同 CVRF 水平的患者亚组中的疗效和安全性。对于疗效分析，逻辑回归用于评估亚组间的治疗相互作用。对于安全性分析，一般关联的 Cochran-Mantel-Haenszel 检验评估了治疗比较； Mantel-Haenszel 比值比评估了显着的治疗效果。结果在这项汇总分析中，共有 4439 名患者接受了 ≥1 剂量的研究药物。基线时共有 3500 名患者（78.8%）的 CVRF ≥1，1833 名患者（41.3%）的 CVRF ≥2。两项试验均达到了主要终点，即 2 小时内头痛消失和最令人烦恼的症状消失。 CVRF 的存在并不影响疗效结果。总体而言，心血管治疗引起的可能出现的不良事件 (TEAE) 发生率较低（lasmiditan，30 例 [0.9%]；安慰剂，5 例 [0.4%]）。无论是否存在任何 CVRF，可能的 CV TEAE 频率均无统计学差异。在 CVRF ≥1、≥2、≥3 或 ≥4 的患者中观察到的唯一可能的 CV TEAE 是心悸。结论当根据 CVRF 的存在进行分析时，lasmiditan 疗效或可能的 CV TEAE 频率没有统计学差异。尽管分析受到单次偏头痛发作设计的限制，但随着 CVRF 数量的增加，疗效和安全性缺乏差异，这表明在 CVRF 患者的治疗方案中可以考虑使用 lasmiditan。需要进一步的研究来评估长期疗效和安全性。试验注册ClinicalTrials.govNCT02439320 (SAMURAI)，于2015年3月18日注册，以及ClinicalTrials.govNCT02605174 (SPARTAN)，于2015年11月11日注册。