{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:46:12Z","timestamp":1787870772625,"version":"build-2784847793"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,7,4]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Sodium glucose cotransporter\u20102 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5\u2009years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11\u2009551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (\u22120.25\u2009mm\u2009Hg [95% CI, \u20130.44 to \u22120.06]), but there was no effect on coefficient of variation (0.02% [95% CI, \u20130.12 to 0.16]) or variability independent of the mean (0.08\u2009U [95% CI, \u20130.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation\u00a0increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02\u20131.38]) and all\u2010cause mortality (HR, 1.12 [95% CI, 1.01\u20131.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit\u2010to\u2010visit SBP variability is independently associated with risks of hospitalization for heart failure and all\u2010cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP\u2010lowering effect.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.028516","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T21:44:55Z","timestamp":1687470295000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-1788","authenticated-orcid":false,"given":"Robert A.","family":"Fletcher","sequence":"first","affiliation":[{"name":"The George Institute for Global Health, UNSW New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9370-9913","authenticated-orcid":false,"given":"Clare","family":"Arnott","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, UNSW New South Wales Sydney Australia"},{"name":"Department of Cardiology Royal Prince Alfred Hospital New South Wales Sydney Australia"},{"name":"Sydney Medical School University of Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-7933","authenticated-orcid":false,"given":"Patrick","family":"Rockenschaub","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Lab for Artificial Intelligence in Medicine Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"QUEST Center for Transforming Biomedical Research Berlin Institute of Health (BIH) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9217-4937","authenticated-orcid":false,"given":"Aletta E.","family":"Schutte","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, UNSW New South Wales Sydney Australia"},{"name":"Faculty of Medicine and Health UNSW New South Wales Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-7502","authenticated-orcid":false,"given":"Lewis","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Health Psychology Section, Institute of Psychiatry, Psychology and Neuroscience King\u2019s College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0885-1953","authenticated-orcid":false,"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women\u2019s Hospital MA Boston USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine and VA Medical Center IN Indianapolis USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-1267","authenticated-orcid":false,"given":"George","family":"Bakris","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Chicago Medicine IL Chicago USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4691-1681","authenticated-orcid":false,"given":"Tara I.","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Stanford University School of Medicine CA Stanford USA"},{"name":"Stanford Hypertension Center Stanford University School of Medicine CA Stanford USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. 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