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

Question 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 m(2) and the risk of all-cause mortality, major adverse cardiovascular events, and end-stage kidney disease in the subsequent 5 years? Findings 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 m(2) 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. Meaning 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 m(2), without increased risk of progression to end-stage kidney disease. 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 m(2) 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 m(2) 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 m(2). 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 m(2) (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. This cohort study investigates the association of renin-angiotensin system blockade therapy discontinuation after estimated glomerular filtration rate decreases with the risk of mortality, major adverse cardiovascular events, and end-stage kidney disease.