Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials
Background Sodium glucose cotransporter‐2 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. Methods and Results Using individual partic...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.028516 |
| _version_ | 1797337864627814400 |
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| author | Robert A. Fletcher Clare Arnott Patrick Rockenschaub Aletta E. Schutte Lewis Carpenter Muthiah Vaduganathan Rajiv Agarwal George Bakris Tara I. Chang Hiddo J. L. Heerspink Meg J. Jardine Kenneth W. Mahaffey Bruce Neal Carol Pollock Min Jun Anthony Rodgers Vlado Perkovic Brendon L. Neuen |
| author_facet | Robert A. Fletcher Clare Arnott Patrick Rockenschaub Aletta E. Schutte Lewis Carpenter Muthiah Vaduganathan Rajiv Agarwal George Bakris Tara I. Chang Hiddo J. L. Heerspink Meg J. Jardine Kenneth W. Mahaffey Bruce Neal Carol Pollock Min Jun Anthony Rodgers Vlado Perkovic Brendon L. Neuen |
| author_sort | Robert A. Fletcher |
| collection | DOAJ |
| description | Background Sodium glucose cotransporter‐2 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. Methods and Results 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 years 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 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg [95% CI, –0.44 to −0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, –0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, –0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02–1.38]) and all‐cause mortality (HR, 1.12 [95% CI, 1.01–1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit‐to‐visit SBP variability is independently associated with risks of hospitalization for heart failure and all‐cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP‐lowering effect. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791. |
| first_indexed | 2024-03-08T09:22:45Z |
| format | Article |
| id | doaj.art-3075bc7abafb43759d117a083ff6e2ac |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-08T09:22:45Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-3075bc7abafb43759d117a083ff6e2ac2024-01-31T11:31:17ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-07-01121310.1161/JAHA.122.028516Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE TrialsRobert A. Fletcher0Clare Arnott1Patrick Rockenschaub2Aletta E. Schutte3Lewis Carpenter4Muthiah Vaduganathan5Rajiv Agarwal6George Bakris7Tara I. Chang8Hiddo J. L. Heerspink9Meg J. Jardine10Kenneth W. Mahaffey11Bruce Neal12Carol Pollock13Min Jun14Anthony Rodgers15Vlado Perkovic16Brendon L. Neuen17The George Institute for Global Health, UNSW New South Wales Sydney AustraliaThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaCharité Lab for Artificial Intelligence in Medicine Charité Universitätsmedizin Berlin Berlin GermanyThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaHealth Psychology Section, Institute of Psychiatry, Psychology and Neuroscience King’s College London London UKCardiovascular Division Brigham and Women’s Hospital MA Boston USAIndiana University School of Medicine and VA Medical Center IN Indianapolis USADepartment of Medicine University of Chicago Medicine IL Chicago USADivision of Nephrology, Department of Medicine Stanford University School of Medicine CA Stanford USAThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaDepartment of Medicine, Stanford Center for Clinical Research Stanford University School of Medicine CA Stanford USAThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaKolling Institute of Medical Research, Sydney Medical School University of Sydney, Royal North Shore Hospital Sydney AustraliaThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaThe George Institute for Global Health, UNSW New South Wales Sydney AustraliaBackground Sodium glucose cotransporter‐2 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. Methods and Results 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 years 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 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg [95% CI, –0.44 to −0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, –0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, –0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02–1.38]) and all‐cause mortality (HR, 1.12 [95% CI, 1.01–1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit‐to‐visit SBP variability is independently associated with risks of hospitalization for heart failure and all‐cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP‐lowering effect. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.https://www.ahajournals.org/doi/10.1161/JAHA.122.028516blood pressure variabilitycanagliflozinclinical outcomesclinical trialsSGLT2 inhibitors |
| spellingShingle | Robert A. Fletcher Clare Arnott Patrick Rockenschaub Aletta E. Schutte Lewis Carpenter Muthiah Vaduganathan Rajiv Agarwal George Bakris Tara I. Chang Hiddo J. L. Heerspink Meg J. Jardine Kenneth W. Mahaffey Bruce Neal Carol Pollock Min Jun Anthony Rodgers Vlado Perkovic Brendon L. Neuen Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease blood pressure variability canagliflozin clinical outcomes clinical trials SGLT2 inhibitors |
| title | Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials |
| title_full | Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials |
| title_fullStr | Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials |
| title_full_unstemmed | Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials |
| title_short | Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials |
| title_sort | canagliflozin blood pressure variability and risk of cardiovascular kidney and mortality outcomes pooled individual participant data from the canvas and credence trials |
| topic | blood pressure variability canagliflozin clinical outcomes clinical trials SGLT2 inhibitors |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.028516 |
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