{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:42:09Z","timestamp":1786372929151,"version":"build-2736575974"},"reference-count":10,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","funder":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Tolvaptan is approved to slow kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. Because\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      studies indicated that the tolvaptan oxobutyric acid metabolite inhibits organic anion\u2013transporting polypeptide (OATP)1B1 and OATP1B3, United States prescribing information advises avoiding concurrent use with OATP1B1\/1B3 substrates, including hepatic hydroxymethyl glutaryl\u2013CoA reductase inhibitors (statins). This\n                      <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                      analysis of the pivotal phase 3 tolvaptan trials (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes [TEMPO] 3:4 trial [NCT00428948] and Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD [REPRISE] trial [NCT02160145]) examined the safety of concurrent tolvaptan\/statin use.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      The trials randomized a combined total of 2815 subjects with early- to late-stage ADPKD to tolvaptan (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =1644) or placebo (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =1171) for 3 years (TEMPO 3:4) and 1 year (REPRISE). Statin use was unrestricted, and 597 subjects (21.2% overall; 332 [20.2%] tolvaptan, 265 [22.6%] placebo) received statins. Statin use (duration, dose change, statin change, permanent discontinuation), incidences of statin-related adverse events, and hepatic transaminase elevations were determined for subjects who received tolvaptan+statin, placebo+statin, tolvaptan alone, and placebo alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No differences in statin use parameters between tolvaptan- and placebo-treated subjects were observed. No statistically significant increases in commonly reported statin-related adverse events (\n                      <jats:italic toggle=\"yes\">e.g.<\/jats:italic>\n                      , musculoskeletal disorders, gastrointestinal symptoms) were seen between subjects receiving tolvaptan+statin and placebo+statin. For example, in TEMPO 3:4, frequencies were 5.4% and 7.8%, respectively, for myalgia (difference \u22122.4%; 95% confidence interval, \u221211.2% to 6.4%) and 9.3% and 7.8%, respectively, for abdominal pain (difference 1.5%; \u22127.9% to 10.9%). In an analysis that excluded participants concurrently using allopurinol, the frequency of alanine transaminase or aspartate transaminase &gt;3\u00d7 upper limit of normal in the pooled study populations was 3.6% for the tolvaptan+statin group and 2.3% for the placebo+statin group (difference 1.4%; \u22122.0% to 4.7%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tolvaptan has been used safely in combination with statins in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Podcast<\/jats:title>\n                    <jats:p>This article contains a podcast at https:\/\/www.asn-online.org\/media\/podcast\/CJASN\/2020_04_06_CJN.08170719.mp3<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.08170719","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T21:45:22Z","timestamp":1585863922000},"page":"643-650","source":"Crossref","is-referenced-by-count":12,"title":["A Post Hoc Analysis of Statin Use in Tolvaptan Autosomal Dominant Polycystic Kidney Disease Pivotal Trials"],"prefix":"10.2215","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct00428948","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02160145","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Susan E.","family":"Shoaf","sequence":"first","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Sergeyeva","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin","family":"Estilo","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Leung","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,4,2]]},"reference":[{"key":"B3-20230813","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1056\/NEJMoa1205511","article-title":"Tolvaptan in patients with autosomal dominant polycystic kidney disease","volume":"367","author":"Torres","year":"2012","journal-title":"N Engl J Med"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1056\/NEJMoa1710030","article-title":"Tolvaptan in later-stage autosomal dominant polycystic kidney disease","volume":"377","author":"Torres","year":"2017","journal-title":"N Engl J Med"},{"key":"B5-20230813","first-page":"259","article-title":"Kidney disease: Improving global outcomes (KDIGO) lipid work group: KDIGO clinical practice guideline for lipid management in chronic kidney disease","volume":"3","year":"2013","journal-title":"Kidney Int 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