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. 2020 May 1;180(5):718-726.
doi: 10.1001/jamainternmed.2020.0193.

Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate

Yao Qiao  1   2 , Jung-Im Shin  1   2 , Teresa K Chen  2   3 , Lesley A Inker  4 , Josef Coresh  1   2 , G Caleb Alexander  1 , John W Jackson  1 , Alex R Chang  5 , Morgan E Grams  1   2   3
Affiliations

Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate

Yao Qiao et al. JAMA Intern Med. .

Abstract

Importance: It is uncertain whether and when angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) treatment should be discontinued in individuals with low estimated glomerular filtration rate (eGFR).

Objective: To investigate the association of ACE-I or ARB therapy discontinuation after eGFR decreases to below 30 mL/min/1.73 m2 with the risk of mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD).

Design, setting, and participants: This retrospective, propensity score-matched cohort study included 3909 patients from an integrated health care system that served rural areas of central and northeastern Pennsylvania. Patients who initiated ACE-I or ARB therapy from January 1, 2004, to December 31, 2018, and had an eGFR decrease to below 30 mL/min/1.73 m2 during therapy were enrolled, with follow-up until January 25, 2019.

Exposures: Individuals were classified based on whether they discontinued ACE-I or ARB therapy within 6 months after an eGFR decrease to below 30 mL/min/1.73 m2.

Main outcomes and measures: The association between ACE-I or ARB therapy discontinuation and mortality during the subsequent 5 years was assessed using multivariable Cox proportional hazards regression models, adjusting for patient characteristics at the time of the eGFR decrease in a propensity score-matched sample. Secondary outcomes included MACE and ESKD.

Results: Of the 3909 individuals receiving ACE-I or ARB treatment who experienced an eGFR decrease to below 30 mL/min/1.73 m2 (2406 [61.6%] female; mean [SD] age, 73.7 [12.6] years), 1235 discontinued ACE-I or ARB therapy within 6 months after the eGFR decrease and 2674 did not discontinue therapy. A total of 434 patients (35.1%) who discontinued ACE-I or ARB therapy and 786 (29.4%) who did not discontinue therapy died during a median follow-up of 2.9 years (interquartile range, 1.3-5.0 years). In the propensity score-matched sample of 2410 individuals, ACE-I or ARB therapy discontinuation was associated with a higher risk of mortality (hazard ratio [HR], 1.39; 95% CI, 1.20-1.60]) and MACE (HR, 1.37; 95% CI, 1.20-1.56), but no statistically significant difference in the risk of ESKD was found (HR, 1.19; 95% CI, 0.86-1.65).

Conclusions and relevance: The findings suggest that continuing ACE-I or ARB therapy in patients with declining kidney function may be associated with cardiovascular benefit without excessive harm of ESKD.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Shin reported receiving grants from Merck outside the submitted work. Dr Chen reported receiving grants from Yale University and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and receiving grant support from a George M. O'Brien Center for Kidney Research Pilot and Feasibility Grant from Yale University and award K08DK117068 from the National Institutes of Health (NIH)/NIDDK. Dr Inker reported receiving grants from the NIH, National Kidney Foundation, Retrophin, Omeros, and Reata Pharmaceuticals and consulting for Tricida Inc. Dr Coresh reported receiving grants from the NIH and the National Kidney Foundation during the conduct of the study. Dr Alexander reported serving as a past chair of the US Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee, serving as a paid adviser to IQVIA, serving as a cofounding principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation, and serving as a member of OptumRx's National P&T Committee. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. Dr Grams reported receiving grants from the NIDDK during the conduct of the study and travel support from Dialysis Clinics Inc outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence of All-Cause Mortality by Angiotensin-Converting Enzyme Inhibitor (ACE-I) and Angiotensin II Receptor Blocker (ARB) Discontinuation Status
eGFR indicates estimated glomerular filtration rate.
Figure 2.
Figure 2.. Cumulative Incidence of Major Adverse Cardiovascular Events (MACE) by Angiotensin-Converting Enzyme Inhibitor (ACE-I) and Angiotensin II Receptor Blocker (ARB) Discontinuation Status
eGFR indicates glomerular filtration rate.
Figure 3.
Figure 3.. Cumulative Incidence of End-stage Kidney Disease (ESKD) Accounting for the Competing Risk of Death by Angiotensin-Converting Enzyme Inhibitor (ACE-I) and Angiotensin II Receptor Blocker (ARB) Discontinuation Status
eGFR indicates estimated glomerular filtration rate.
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