{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:39:54Z","timestamp":1788982794105,"version":"build-2803163510"},"reference-count":89,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T00:00:00Z","timestamp":1710547200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014848","name":"Arnold Ventures","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Due to encouraging pre\u2010clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin\u2010converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer.<\/jats:p><jats:p>We sought to investigate the anti\u2010cancer effects of drugs repurposed from cardiology or anti\u2010inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG\u2010CoA reductase inhibitors (statins), cyclo\u2010oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin\u2010converting enzyme inhibitors. We also included non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a systematic literature review using PubMed and Web of Science with search terms including \u201caspirin,\u201d \u201cNSAID,\u201d \u201cstatin\u201d (including specific statin drug names), \u201cmetformin,\u201d \u201cACE inhibitors,\u201d and \u201cARBs\u201d (including specific anti\u2010hypertensive drug names) in combination with \u201ccancer.\u201d Searches were limited to human studies published between 2000 and 2023.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The number and percentage of studies reported positive results and pooled estimates of overall survival, progression\u2010free survival, response, and disease\u2010free survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (<jats:italic>n<\/jats:italic>\u2009=\u200921; 30.9%), celecoxib (<jats:italic>n<\/jats:italic>\u2009=\u200920; 29.4%), and simvastatin (<jats:italic>n<\/jats:italic>\u2009=\u20098; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non\u2010small\u2010cell lung cancer (<jats:italic>n<\/jats:italic>\u2009=\u200919; 27.9%); breast (<jats:italic>n<\/jats:italic>\u2009=\u20098; 20.6%), colorectal (<jats:italic>n<\/jats:italic>\u2009=\u20097; 10.3%), and hepatocellular (<jats:italic>n<\/jats:italic>\u2009=\u20096; 8.8%). Most studies were conducted in a phase II trial (<jats:italic>n<\/jats:italic>\u2009=\u200938; 55.9%). Most studies were tested in metastatic cancers (<jats:italic>n<\/jats:italic>\u2009=\u200949; 72.1%) and in the first\u2010line setting (<jats:italic>n<\/jats:italic>\u2009=\u200936; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression\u2010free survival (86.1% of studies testing progression\u2010free survival) or in overall survival (94.3% of studies testing overall survival). Progression\u2010free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression\u2010free survival was worse in one study (2.8% of studies testing progression\u2010free survival).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Despite promising pre\u2010clinical and population\u2010based data, cardiovascular drugs and anti\u2010inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7049","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T07:55:25Z","timestamp":1710575725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Cardiovascular\/anti\u2010inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta\u2010analysis of randomized trials"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-886X","authenticated-orcid":false,"given":"David J.","family":"Benjamin","sequence":"first","affiliation":[{"name":"Hoag Family Cancer Institute  Newport Beach California 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