Is there an association between discontinuing renin-angiotensin system blockade after estimated glomerular filtration rate (eGFR) decreases to less than 30 mL/min/1.73 m2 and the risk of all-cause mortality, major adverse cardiovascular events, and end-stage kidney disease in the subsequent 5 years?
In this cohort study of 3909 individuals who had initiated angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy and experienced an eGFR decrease to below 30 mL/min/1.73 m2 during therapy, 35.1% of those who discontinued therapy within 6 months after the eGFR decrease died during the subsequent 5 years compared with 29.4% of those who did not discontinue therapy.
These findings suggest that continued angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use is associated with cardiovascular health benefits in individuals with an eGFR below 30 mL/min/1.73 m2, without increased risk of progression to end-stage kidney disease.
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).
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.
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.
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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Qiao Y, Shin J, Chen TK, et al. Association Between Renin-Angiotensin System Blockade Discontinuation and All-Cause Mortality Among Persons With Low Estimated Glomerular Filtration Rate. JAMA Intern Med. 2020;180(5):718–726. doi:10.1001/jamainternmed.2020.0193
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