Acute increases in serum creatinine after starting angiotensin-converting enzyme inhibitor-based therapy and effects of its continuation on major clinical outcomes in type 2 diabetes mellitus
Author(s)
Type
Journal Article
Abstract
Discontinuation of angiotensin-converting enzyme (ACE) inhibitor is recommended if patients experience ≥30% acute increase in serum creatinine after starting this therapy. However, the long-term effects of its continuation or discontinuation on major clinical outcomes after increases in serum creatinine are unclear. In the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation), 11 140 diabetes mellitus patients were randomly assigned to perindopril-indapamide or placebo after a 6-week active run-in period. The current study included 11 066 participants with 2 serum creatinine measurements recorded before and during the active run-in period (3 weeks apart). Acute increase in creatinine was determined using these 2 measurements and classified into 4 groups: increases in serum creatinine of <10%, 10% to 19%, 20% to 29%, and ≥30%. The primary study outcome was the composite of major macrovascular events, new or worsening nephropathy, and all-cause mortality. An acute increase in serum creatinine was associated with an elevated risk of the primary outcome ( P for trend <0.001). The hazard ratios were 1.11 (95% CI, 0.97-1.28) for those with an increase of 10% to 19%, 1.34 (1.07-1.66) for 20% to 29%, and 1.44 (1.15-1.81) for ≥30%, compared with <10%. However, there was no evidence of heterogeneity in the benefit of randomized treatment effects on the outcome across subgroups defined by acute serum creatinine increase ( P for heterogeneity=0.94). Acute increases in serum creatinine after starting perindopril-indapamide were associated with greater risks of subsequent major clinical outcomes. However, the continuation of angiotensin-converting enzyme inhibitor-based therapy reduced the long-term risk of major clinical outcomes, irrespective of acute increase in creatinine. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00145925.
Date Issued
2019-01-01
Online Publication Date
2019-05-27T06:00:19Z
Date Acceptance
2018-10-25
ISSN
0194-911X
Publisher
American Heart Association
Start Page
84
End Page
91
Journal / Book Title
Hypertension
Volume
73
Issue
1
Copyright Statement
© 2018 American Heart Association, Inc. This is a non-final version of an article published in final form in Hypertension 2019; 73: 84–91 https://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12060
Source Database
pubmed
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30571562
Subjects
angiotensin-converting enzyme inhibitors
cardiovascular diseases
diabetes mellitus
kidney diseases
renin-angiotensin system
ADVANCE Collaborative Group
1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Cardiovascular System & Hematology
Publication Status
Published
Country
United States
Date Publish Online
2018-11-27