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Lasmiditan, a selective 5\u2010hydroxytryptamine (5\u2010HT)\n                      <jats:sub>1<\/jats:sub>\n                      F receptor agonist without vasoconstrictive properties, may offer a safer alternative to triptans for these patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this systematic review and meta\u2010analysis, we systematically searched MEDLINE, Embase, Scopus, and Cochrane CENTRAL from inception to June 2025 following a retrospectively registered International Prospective Register of Systematic Reviews protocol (CRD420251208584). Primary outcomes were pain freedom at 2\u2009h (efficacy; randomized controlled trials) and major adverse CV events (observational studies). Random\u2010effects meta\u2010analyses used odds ratios (ORs) for binary efficacy outcomes and hazard ratios for time\u2010to\u2010event safety data. Rare cardiac adverse events were analyzed using Peto ORs. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixteen studies were included (six lasmiditan studies involving three randomized controlled trials [two phase 3 and one phase 2] enrolling 5126 participants, two\n                      <jats:italic>post hoc<\/jats:italic>\n                      analyses, one open\u2010label extension, and 10 triptan CV safety studies). In the meta\u2010analysis of three independent randomized controlled trials (eight dose\u2010specific comparisons), lasmiditan significantly increased pain freedom at 2\u2009h versus placebo (OR, 2.09; 95% confidence interval [CI], 1.66\u20132.63,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; heterogeneity statistic (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      ) =\u200958.9%; GRADE: high certainty), with clear dose\u2010dependent effects (50\u2009mg OR \u2248\u20091.50; 100\u2009mg OR \u2248\u20092.0; 200\u2009mg OR \u2248\u20092.60; subgroup\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and number needed to treat of 4.1\u201315.4. Most bothersome symptom freedom was similarly improved (OR, 1.79; 95% CI, 1.45\u20132.22,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200954.5%; GRADE: high certainty). Observational triptan safety data (14 comparisons from 10 studies) showed apparent CV protection (hazard ratio, 0.82; 95% CI, 0.73\u20130.92), although certainty was very low due to confounding by indication, inconsistency (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200982.4%), and comparator indirectness. Cardiac treatment\u2010emergent adverse events were rare with lasmiditan (&lt;1%; Peto OR, 3.14; 95% CI, 1.10\u20138.98, based on 14 total events; GRADE: low certainty), with zero vasoconstrictive CV events across all trials. Common adverse events included dizziness (risk ratio [relative risk] [RR], 5.71), somnolence (RR, 2.68), and paresthesia (RR, 5.02), all dose\u2010dependent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lasmiditan demonstrated efficacy and favorable CV safety in CV\u2010risk populations, with no vasoconstrictive events detected across 5126 participants. Common central nervous system adverse effects, particularly dizziness, require careful patient counseling. The recent voluntary market withdrawal of lasmiditan underscores the need for continued development and evaluation of non\u2010vasoconstrictive acute migraine treatments for patients with CV contraindications to triptans.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/head70182-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.70182","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:22:08Z","timestamp":1789104128000},"page":"2156-2172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and cardiovascular safety of lasmiditan in patients with cardiovascular risk factors: A systematic review and meta\u2010analysis with updated synthesis of triptan safety data"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2421-3953","authenticated-orcid":false,"given":"Shankar","family":"Biswas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Ivano\u2010Frankivsk National Medical University  Ivano\u2010Frankivsk Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8448-8035","authenticated-orcid":false,"given":"Sindhu","family":"Vasireddy","sequence":"additional","affiliation":[{"name":"Specialist Neurology, Department of Neurology NMC Specialty Hospital  Abu Dhabi United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashasvi","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ivano\u2010Frankivsk National Medical University  Ivano\u2010Frankivsk Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruv","family":"Gehlot","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ananta Institute of Medical Sciences and Research Centre  Rajsamand Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Fasil","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Bangalore Baptist Hospital  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira A.","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Sree Balaji Medical College and Hospital  Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. 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