{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:32:45Z","timestamp":1792269165674,"version":"4.4.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2014,9,22]],"date-time":"2014-09-22T00:00:00Z","timestamp":1411344000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18\u20134.41; I\n                      <jats:sup>2\u2009<\/jats:sup>\n                      =\u20090%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52\u20131.43; I\n                      <jats:sup>2\u2009<\/jats:sup>\n                      =\u200924.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64\u20131.26), and the second one suggested an increased risk of 2.51 (1.10\u20135.71). In this case, because of the high degree of heterogeneity, results were not pooled.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0333102414550416","type":"journal-article","created":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T02:58:58Z","timestamp":1411441138000},"page":"118-131","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":148,"title":["Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: Systematic review of observational studies"],"prefix":"10.1177","volume":"35","author":[{"given":"G","family":"Roberto","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Raschi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Piccinni","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Conti","sequence":"additional","affiliation":[{"name":"Regional Centre for Pharmacovigilance, Lombardy Region, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Vignatelli","sequence":"additional","affiliation":[{"name":"Local Health Trust of Bologna, Italy; Health and Social Regional Agency of Emilia-Romagna Region, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"D\u2019Alessandro","sequence":"additional","affiliation":[{"name":"IRCCS, Institute of Neurological Sciences of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"De Ponti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Poluzzi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,9,22]]},"reference":[{"key":"bibr1-0333102414550416","unstructured":"Atlas of headache disorders and resources in the world 2011\u2014World Health Organization. World Health Organization, http:\/\/www.who.int\/mental_ health\/management\/atlas_headache_disorders\/en\/ (accessed April 2014)."},{"key":"bibr2-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1007\/s10194-012-0437-6"},{"key":"bibr3-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMct0910887"},{"key":"bibr4-0333102414550416","unstructured":"Diagnosis and management of headache in adults. Scottish Intercollegiate Guidelines Network, http:\/\/www.sign.ac.uk\/guidelines\/fulltext\/107\/ (accessed April 2014)."},{"key":"bibr5-0333102414550416","unstructured":"Cafergot\u00ae\u2014Sandoz Inc. Food and Drug Administration, http:\/\/labels.fda.gov\/getProprietaryName.cfm (accessed April 2014)."},{"key":"bibr6-0333102414550416","unstructured":"IMITREX\u00ae\u2014GlaxoSmithKline LLC. Food and Drug Administration, http:\/\/labels.fda.gov\/getProprietaryName.cfm (accessed April 2014)."},{"key":"bibr7-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2008.01578.x"},{"key":"bibr8-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-003-0011-7"},{"key":"bibr9-0333102414550416","first-page":"199","volume":"45","author":"Villal\u00f3n CM","year":"2002","journal-title":"Proc West Pharmacol Soc"},{"key":"bibr10-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413508661"},{"key":"bibr11-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.01007.x"},{"key":"bibr12-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2008.09.030"},{"key":"bibr13-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413499649"},{"key":"bibr14-0333102414550416","unstructured":"Roberto G, Raschi E, Piccinni C, et\u00a0al. Adverse cardiovascular events associated to triptans and ergotamines for the acute treatment of migraine: A systematic review of observational studies. PROSPERO 2014: CRD42014007528, http:\/\/www.crd.york.ac.uk\/PROSPERO\/display_record.asp?ID=CRD42014007528 (accessed April 2014)."},{"key":"bibr15-0333102414550416","doi-asserted-by":"crossref","unstructured":"Bigal ME. Migraine and cardiovascular disease.\n                      Arq Neuropsiquiatr\n                      2011; 69: 122\u2013129.","DOI":"10.1590\/S0004-282X2011000100023"},{"key":"bibr16-0333102414550416","doi-asserted-by":"crossref","unstructured":"Spector JT, Kahn SR, Jones MR, et\u00a0al. Migraine headache and ischemic stroke risk: An updated meta-analysis.\n                      Am J Med\n                      2010; 123: 612\u2013624.","DOI":"10.1016\/j.amjmed.2009.12.021"},{"key":"bibr17-0333102414550416","unstructured":"Wells GA, Shea B, O\u2019Connell D, et\u00a0al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute. http:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp (2014, accessed March 2014)."},{"key":"bibr18-0333102414550416","unstructured":"Higgins JPT and Green S (eds)\n                      Cochrane handbook for systematic reviews of interventions.\n                      Version 5.1.0. The Cochrane Collaboration, 2011."},{"key":"bibr19-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.15.2008"},{"key":"bibr20-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.epirev.a036298"},{"key":"bibr21-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"bibr22-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0127-6"},{"key":"bibr23-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2004.04122.x"},{"key":"bibr24-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000240128.76399.fa"},{"key":"bibr25-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0332-2"},{"key":"bibr26-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.00937.x"},{"key":"bibr27-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000110312.36809.7F"},{"key":"bibr28-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.09.006"},{"key":"bibr29-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1016\/S0890-6238(03)00012-1"},{"key":"bibr30-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.240"},{"key":"bibr31-0333102414550416","unstructured":"VIRDEX\u00ae\u2014FULTON medicinali S.p.A. Agenzia Italiana del Farmaco, https:\/\/farmaci.agenziafarmaco.gov.it\/aifa\/servlet\/PdfDownloadServlet?pdfFileName=footer_001002_012437_RCP.pdf&retry=0 (accessed April 2014)."},{"key":"bibr32-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328360d596"},{"key":"bibr33-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2009.01595.x"},{"key":"bibr34-0333102414550416","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-011-0651-z"},{"key":"bibr35-0333102414550416","unstructured":"Nota Informativa Importante\u2014RELPAX (Eletriptan bromidrato). Agenzia Italiana del Farmaco, http:\/\/www.agenziafarmaco.gov.it\/sites\/default\/files\/DHPC_Relpax_Rev%20AIFA+SSCFV-CTS_final.pdf (accessed April 2014)."},{"key":"bibr36-0333102414550416","unstructured":"Google Scholar. Google, http:\/\/scholar.google.com\/ (accessed April 2014)."},{"key":"bibr37-0333102414550416","unstructured":"Gomes C, Camacho X, Martins D, et\u00a0al. Triptans for migraine therapy: A pharmacoepidemiologic analysis. Ontario Drug Policy Research Network, http:\/\/www.odprn.ca\/wp-content\/uploads\/2014\/02\/Triptans-Pharmacoepidemiology-Report-CENSORED-for-review.pdf (accessed April 2014)."}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0333102414550416","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0333102414550416","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0333102414550416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:46:33Z","timestamp":1777387593000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0333102414550416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,22]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1177\/0333102414550416"],"URL":"https:\/\/doi.org\/10.1177\/0333102414550416","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,22]]}}}