Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial
Background The DAPA‐CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We a...
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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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.122.028739 |
| _version_ | 1797822344793686016 |
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| author | Glenn M. Chertow Ricardo Correa‐Rotter Priya Vart Niels Jongs John J. V. McMurray Peter Rossing Anna Maria Langkilde C. David Sjöström Robert D. Toto David C. Wheeler Hiddo J. L. Heerspink |
| author_facet | Glenn M. Chertow Ricardo Correa‐Rotter Priya Vart Niels Jongs John J. V. McMurray Peter Rossing Anna Maria Langkilde C. David Sjöström Robert D. Toto David C. Wheeler Hiddo J. L. Heerspink |
| author_sort | Glenn M. Chertow |
| collection | DOAJ |
| description | Background The DAPA‐CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. Methods and Results We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end‐stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all‐cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin‐angiotensin‐aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin‐angiotensin‐aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β‐adrenergic antagonists (39.0%), diuretics (43.7%), and antithrombotic (47.4%), and lipid‐lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. Conclusions The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications. Registration Information clinicaltrials.gov. Identifier: NCT03036150. |
| first_indexed | 2024-03-13T10:07:39Z |
| format | Article |
| id | doaj.art-9826f32decaf40029c4ae4917e251524 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-13T10:07:39Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-9826f32decaf40029c4ae4917e2515242023-05-22T11:33:50ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-05-0112910.1161/JAHA.122.028739Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD TrialGlenn M. Chertow0Ricardo Correa‐Rotter1Priya Vart2Niels Jongs3John J. V. McMurray4Peter Rossing5Anna Maria Langkilde6C. David Sjöström7Robert D. Toto8David C. Wheeler9Hiddo J. L. Heerspink10Departments of Medicine, Epidemiology and Population Health, and Health Policy Stanford University School of Medicine Stanford CAInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City MexicoDepartment of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Centre Groningen Groningen The NetherlandsDepartment of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Centre Groningen Groningen The NetherlandsInstitute of Cardiovascular and Medical Sciences University of Glasgow Glasgow UKSteno Diabetes Center Copenhagen Herlev DenmarkLate‐Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D AstraZeneca Gothenburg SwedenLate‐Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D AstraZeneca Gothenburg SwedenDepartment of Internal Medicine UT Southwestern Medical Center Dallas TXDepartment of Renal Medicine University College London London UKDepartment of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Centre Groningen Groningen The NetherlandsBackground The DAPA‐CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. Methods and Results We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end‐stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all‐cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin‐angiotensin‐aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin‐angiotensin‐aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β‐adrenergic antagonists (39.0%), diuretics (43.7%), and antithrombotic (47.4%), and lipid‐lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. Conclusions The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications. Registration Information clinicaltrials.gov. Identifier: NCT03036150.https://www.ahajournals.org/doi/10.1161/JAHA.122.028739cardiovascular medicationschronic kidney diseasedapagliflozinSGLT2 inhibitors |
| spellingShingle | Glenn M. Chertow Ricardo Correa‐Rotter Priya Vart Niels Jongs John J. V. McMurray Peter Rossing Anna Maria Langkilde C. David Sjöström Robert D. Toto David C. Wheeler Hiddo J. L. Heerspink Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiovascular medications chronic kidney disease dapagliflozin SGLT2 inhibitors |
| title | Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial |
| title_full | Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial |
| title_fullStr | Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial |
| title_full_unstemmed | Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial |
| title_short | Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA‐CKD Trial |
| title_sort | effects of dapagliflozin in chronic kidney disease with and without other cardiovascular medications dapa ckd trial |
| topic | cardiovascular medications chronic kidney disease dapagliflozin SGLT2 inhibitors |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.028739 |
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