{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:48:56Z","timestamp":1786373336208,"version":"build-2736575974"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["211086"],"award-info":[{"award-number":["211086"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["358395"],"award-info":[{"award-number":["358395"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["571281"],"award-info":[{"award-number":["571281"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["APP1149987"],"award-info":[{"award-number":["APP1149987"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["APP1174120"],"award-info":[{"award-number":["APP1174120"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor\u2013based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to &lt;5.0 mEq\/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (\u22655.0 mEq\/L), normokalemia, and hypokalemia (&lt;3.5 mEq\/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor\u2013based therapy or placebo; major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor\u2013based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years; hazard ratio, 0.91; 95% confidence interval, 0.83 to 1.00;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.04) compared with placebo. The magnitude of effects did not differ across subgroups defined by short-term changes in serum potassium during run-in (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      for heterogeneity =0.66). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, major coronary events, major cerebrovascular events, and new or worsening nephropathy (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      for heterogeneity \u22650.27).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Continuation of angiotensin-converting enzyme inhibitor\u2013based therapy consistently decreased the subsequent risk of clinical outcomes, including cardiovascular and kidney outcomes and death, regardless of short-term changes in serum potassium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry name and registration number:<\/jats:title>\n                    <jats:p>Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), NCT00145925<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.00180122","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T01:51:18Z","timestamp":1658973078000},"page":"1139-1149","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Short-Term Changes in Serum Potassium and the Risk of Subsequent Vascular Events and Mortality"],"prefix":"10.2215","volume":"17","clinical-trial-number":[{"clinical-trial-number":"nct00145925","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Toshiaki","family":"Ohkuma","sequence":"first","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Harrap","sequence":"additional","affiliation":[{"name":"Department of Physiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mancia","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano, University of Milan-Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Marre","sequence":"additional","affiliation":[{"name":"Hopital Bichat-Claude Bernard, Universite Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushka","family":"Patel","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, 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