Renin-angiotensin-system inhibitors (RASi: Renin-angiotensin-system inhibitors), which include angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) reduce proteinuria, delay the progression of chronic kidney disease (CKD), and protect against cardiovascular events and hospitalizations on the background of heart failure.
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In a study whose findings were published in the journal ‘eClinicalMedicine’, the researchers examined whether there is a relationship between stopping treatment with ACEi/ARBs and the risk of clinical outcomes in patients with type 2 diabetes (T2D) and advanced CKD (estimated glomerular filtration rate [eGFR] < 30 מיליליטר/דקה/1.73 מטר רבוע).
For this purpose, the researchers conducted a population-based prospective cohort study, including 10,400 T2D patients from Hong Kong. Study participants were stratified based on continued treatment with ACEi/ARBs within 6 months after reaching an eGFR < 30 ml/min/1.73 m2, starting from January 1, 2002 to December 31, 2018. The follow-up period continued until December 31 2019.
The primary outcomes of the study included mortality, major-adverse cardiovascular events (MACE), heart failure, end-stage renal disease (ESKD), and all-cause mortality. The researchers used a Cox model with time-dependent exposure and side variables to estimate the hazard ratio of the outcomes in the cohort propensity-score overlap-weighted. The risk of occurrence of hyperkalemia (plasma potassium > 5.5 mmol/L) in patients who stopped treatment with ACEi/ARBs compared to those who continued to receive ACEi/ARBs was evaluated in a register-based cohort.
In the population-based cohort of 10,400 patients receiving ACEi/ARBs with a new value of eGFR < 30 mL/min/1.73 m2, 1,766 (17.0%) discontinued ACEi/ARB therapy and 8,634 (83.0%) continued therapy. During a median follow-up period of 3.6 (interquartile range, 2.11-5.8) years (41,623 person-years), 13.5%, 12.9%, and 27.6% had MACE, heart failure, and ESKD events, respectively, and 35.8% died . Discontinuation of ACEi/ARBs was associated with an increased risk of MACE (hazard ratio = 1.27, 95% CI 1.08-1.49), heart failure (hazard ratio = 1.85, 95% CI 1.53-2.25 ), ESKD (hazard ratio = 1.30, 95% confidence interval 1.17-1.43), and neutral risk for mortality from any cause (hazard ratio = 0.93, 95% confidence interval 0.86-1.01), compared to patients who continued the treatment In a register-based cohort (583 patients who stopped receiving ACEi/ARBs and 3,817 who continued treatment with ACEi/ARBs), those who stopped treatment had a neutral risk of hyperkalemia (hazard ratio = 0.95, 95% confidence interval -0.84 1.08).
In conclusion, in type 2 diabetic patients with advanced CKD, discontinuation of ACEi/ARBs was associated with an increased risk of cardiovascular and renal events. The researchers’ findings support the continuation of treatment for these patients.
source:
Yang A, Shi M, Lau ESH, Wu H, Zhang X, Fan B, Kong APS, Luk AOY, Ma RCW, Chan JCN, Chow E. Clinical outcomes following discontinuation of renin-angiotensin-system inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: A prospective cohort study. EClinicalMedicine. 2022 Nov 24;55:101751. doi: 10.1016/j.eclinm.2022.101751. PMID: 36457651; PMCID: PMC9706514.