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As a putative class IV action, central nervous system modulation was discussed. The development and approval of novel antiarrhythmic compounds subsequently required more refined subdivision of class I action and a fourth class of action, i.e. \u2018Ca\n                    <jats:sup>2+<\/jats:sup>\n                    antagonism\u2019 as exemplified by verapamil. For half a century, this simple and easy to remember classification has served as an orientation for students and clinicians alike. Nevertheless, it has also been criticised for not being sufficiently systematic and for failing to predict the increased mortality when applied post-myocardial infarction for prevention of sudden cardiac death as published in the Cardiac Arrhythmia Suppression Trial. To overcome this seeming shortcoming, the consensus of the European task force led to a more extensive classification (\u2018The Sicilian Gambit\u2019), with complete listing of multiple actions of the individual antiarrhythmic drugs known at that time. The resulting classification was never widely embraced by cardiologists, most likely due to its inherent complexity. Recently, the original Vaughan Williams classification of AAD action has been expanded in order to reflect today\u2019s improved knowledge about arrhythmia mechanisms and to include novel targets for AAD actions, but at the same time, the basic concept that proved so useful in the clinical management remained conserved.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05861-1","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T03:00:23Z","timestamp":1788750023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Edward Miles Vaughan Williams\u2019 classification of antiarrhythmic drugs: then and now"],"prefix":"10.1007","author":[{"given":"Anthony","family":"Cot\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9mi","family":"Peyronnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Ravens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"5861_CR35","doi-asserted-by":"publisher","unstructured":"Antoons G, Sipido KR (2008) Targeting calcium handling in arrhythmias. 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