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

ADVANCE Collaborative Group

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3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)84-91
Number of pages8
JournalHypertension (Dallas, Tex. : 1979)
Volume73
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

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Angiotensin-Converting Enzyme Inhibitors
Type 2 Diabetes Mellitus
Creatinine
Serum
Indapamide
Perindopril
Therapeutics
perindopril drug combination indapamide
Gliclazide
Vascular Diseases
Diabetes Mellitus
Placebos
Outcome Assessment (Health Care)
Clinical Trials
Mortality

Cite this

@article{f5d8f9a5ac554a358a83e09efbca7b6e,
title = "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",
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.",
author = "{ADVANCE Collaborative Group} and Toshiaki Ohkuma and Min Jun and Anthony Rodgers and Cooper, {Mark E.} and Paul Glasziou and Pavel Hamet and Stephen Harrap and Giuseppe Mancia and Michel Marre and Bruce Neal and Vlado Perkovic and Neil Poulter and Bryan Williams and Sophia Zoungas and John Chalmers and Mark Woodward",
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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. / ADVANCE Collaborative Group.

In: Hypertension (Dallas, Tex. : 1979), Vol. 73, No. 1, 01.01.2019, p. 84-91.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 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

AU - ADVANCE Collaborative Group

AU - Ohkuma, Toshiaki

AU - Jun, Min

AU - Rodgers, Anthony

AU - Cooper, Mark E.

AU - Glasziou, Paul

AU - Hamet, Pavel

AU - Harrap, Stephen

AU - Mancia, Giuseppe

AU - Marre, Michel

AU - Neal, Bruce

AU - Perkovic, Vlado

AU - Poulter, Neil

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AU - Zoungas, Sophia

AU - Chalmers, John

AU - Woodward, Mark

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