Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes

Background Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin‐converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin‐converting enzyme inhibitors with other antihypertensive agents modifies the...

Full description

Saved in:
Bibliographic Details
Main Authors: Elaine Ku, Kenneth Jamerson, Timothy P. Copeland, Charles E. McCulloch, Hocine Tighiouart, Mark J. Sarnak
Format: Article
Language:English
Published: Wiley 2024-08-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.035177
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850198441873899520
author Elaine Ku
Kenneth Jamerson
Timothy P. Copeland
Charles E. McCulloch
Hocine Tighiouart
Mark J. Sarnak
author_facet Elaine Ku
Kenneth Jamerson
Timothy P. Copeland
Charles E. McCulloch
Hocine Tighiouart
Mark J. Sarnak
author_sort Elaine Ku
collection DOAJ
description Background Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin‐converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin‐converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. Methods and Results We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow‐up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07–1.48). In spline‐based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm. Conclusion Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.
format Article
id doaj-art-be41ba10137b478f82eacae96dd6de62
institution OA Journals
issn 2047-9980
language English
publishDate 2024-08-01
publisher Wiley
record_format Article
series Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
spelling doaj-art-be41ba10137b478f82eacae96dd6de622025-08-20T02:12:53ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-08-01131510.1161/JAHA.124.035177Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular OutcomesElaine Ku0Kenneth Jamerson1Timothy P. Copeland2Charles E. McCulloch3Hocine Tighiouart4Mark J. Sarnak5Division of Nephrology, Department of Medicine University of California San Francisco CADepartment of Medicine, Division of Cardiovascular Medicine University of Michigan Ann‐Arbor Ann‐Arbor MIDivision of Nephrology, Department of Medicine University of California San Francisco CADepartment of Epidemiology &amp; Biostatistics University of California San Francisco CAInstitute for Clinical Research and Health Policy Studies Tufts Medical Center Boston MATufts Clinical and Translational Science Institute Tufts University Boston MABackground Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin‐converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin‐converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. Methods and Results We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow‐up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07–1.48). In spline‐based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm. Conclusion Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.https://www.ahajournals.org/doi/10.1161/JAHA.124.035177antihypertensive therapycardiovascular diseasehypertension
spellingShingle Elaine Ku
Kenneth Jamerson
Timothy P. Copeland
Charles E. McCulloch
Hocine Tighiouart
Mark J. Sarnak
Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
antihypertensive therapy
cardiovascular disease
hypertension
title Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes
title_full Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes
title_fullStr Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes
title_full_unstemmed Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes
title_short Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes
title_sort acute declines in estimated glomerular filtration rate in patients treated with benazepril and hydrochlorothiazide versus amlodipine and risk of cardiovascular outcomes
topic antihypertensive therapy
cardiovascular disease
hypertension
url https://www.ahajournals.org/doi/10.1161/JAHA.124.035177
work_keys_str_mv AT elaineku acutedeclinesinestimatedglomerularfiltrationrateinpatientstreatedwithbenazeprilandhydrochlorothiazideversusamlodipineandriskofcardiovascularoutcomes
AT kennethjamerson acutedeclinesinestimatedglomerularfiltrationrateinpatientstreatedwithbenazeprilandhydrochlorothiazideversusamlodipineandriskofcardiovascularoutcomes
AT timothypcopeland acutedeclinesinestimatedglomerularfiltrationrateinpatientstreatedwithbenazeprilandhydrochlorothiazideversusamlodipineandriskofcardiovascularoutcomes
AT charlesemcculloch acutedeclinesinestimatedglomerularfiltrationrateinpatientstreatedwithbenazeprilandhydrochlorothiazideversusamlodipineandriskofcardiovascularoutcomes
AT hocinetighiouart acutedeclinesinestimatedglomerularfiltrationrateinpatientstreatedwithbenazeprilandhydrochlorothiazideversusamlodipineandriskofcardiovascularoutcomes
AT markjsarnak acutedeclinesinestimatedglomerularfiltrationrateinpatientstreatedwithbenazeprilandhydrochlorothiazideversusamlodipineandriskofcardiovascularoutcomes