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

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 m 2 with the risk of mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD). DESIGN, SETTING, AND PARTICIPANTSThis 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 MEASURESThe 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. RESULTSOf 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 RELEVANCEThe 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.

Clinical Management of Hyperkalemia

“…61,62 Despite a lack of randomized controlled trial data to document improved clinical outcomes with correction of hyperkalemia and reinitiation of RAASi therapy in patients with an increased hyperkalemia risk, there is an increasing body of real-world evidence of increased morbidity and mortality among patients with CKD, HF, or diabetes who receive suboptimal or no RAASi therapy because of hyperkalemia. [63][64][65] For example, in a cohort study of patients who experienced a decline in eGFR to less than 30 mL/min per 1.73 m 2 while receiving RAASi therapy, discontinuation of RAASi therapy was associated with a higher risk of mortality or major adverse cardiovascular events than continuation of RAA-Sis. 63 In addition, a recent consensus report 9 and a position paper 66 suggest that treatment with the newer K þ binders (discussed subsequently) may allow for optimization of RAASi therapy in patients with HF.…”

“…[63][64][65] For example, in a cohort study of patients who experienced a decline in eGFR to less than 30 mL/min per 1.73 m 2 while receiving RAASi therapy, discontinuation of RAASi therapy was associated with a higher risk of mortality or major adverse cardiovascular events than continuation of RAA-Sis. 63 In addition, a recent consensus report 9 and a position paper 66 suggest that treatment with the newer K þ binders (discussed subsequently) may allow for optimization of RAASi therapy in patients with HF. Therefore, maximum RAASi therapy, as tolerated, should be considered when RAASis are indicated.…”

Speculation is not evidence: antihypertensive therapy and COVID-19

“…Hypertension carries a population-attributable risk of 35-40% for cardiovascular disease, 20 and ACE inhibitors and ARBs are the most potent weapons that we have to fight against this killer. Disseminating speculations about a hypothetical risk associated with these medications, which does not have evidence or even strong pathophysiological support, does not help and in fact opens up the deleterious possibility of giving wrong and potentially dangerous recommendations to our patients, 21 in a perspective dictated by defensive medicine. I think that doctors and major journals should be careful in raising speculation without a strong pathophysiological rationale, with potential devastating effects on public health programmes and individual well-being.…”

Encountering COVID-19 as Endocrinologists

“…Regarding treatment, concerns have been raised regarding a possible increased risk for adverse outcomes in patients using ACE inhibitors or angiotensin receptor blockers, which can increase the expression level of ACE2 receptors [14]. However, it is not recommended to discontinue these agents due to a lack of sufficient evidence, and because doing so can also worsen cardiovascular or kidney disease [15,16].…”