For patients whose estimated glomerular filtration rate (eGFR) declines to less than 30 mL/min/1.73 m2, continuing treatment with renin-angiotensin system blockers has continued cardiovascular benefits, suggests a study in JAMA Internal Medicine.
Using data from a large integrated healthcare system in Pennsylvania, the researchers identified approximately 163,000 patients who started angiotensin-converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB) therapy between 2004 and 2018. Of these, nearly 11,000 patients subsequently had a drop in outpatient eGFR to less than 30 mL/min/1.73 m2. After elimination of patients who discontinued ACEI/ARB therapy before the drop in kidney function (and other exclusion criteria), the study population included 3909 patients: 61.6% female, mean age 73.7 years. Of these, about 31.6% discontinued ACEIs/ARBs within 6 months after the reduction in eGFR.
On propensity score matching, the researchers identified 1205 patients who discontinued ACEI/ARB therapy and 1205 controls who continued on treatment. The main outcome of interest was the association between ACEI/ARB discontinuation and mortality over the subsequent 5 years. Analyses were adjusted for patient characteristics at the time of the drop in kidney function.
In the overall study population, median follow-up was 2.9 years. Mortality was 35.1% for patients who discontinued ACEIs/ARBs and 29.4% for controls who continued therapy. The increase in mortality associated with discontinuation remained significant in the propensity-matched analysis: 40.0% versus 34.0%, hazard ratio (HR) 1.39. Discontinuation was also associated with an increased risk of major adverse cardiovascular events: HR 1.37.
Risk of developing kidney failure was about 7% in both groups. The presence of baseline diabetes had a modifying effect on the association between ACEI/ARB and risk of kidney failure: estimated HR 1.56 in patients with diabetes versus 0.61 in those without. Discontinuation of ACEI/ARB therapy was associated with a lower risk of hyperkalemia: HR 0.65. Analysis of ACEI/ARB discontinuation after eGFR decrease by 40% or more also showed significant increases in the risk of death or cardiovascular events: HR 1.53 and 1.40, respectively.
Patients with lower eGFR are more likely to experience adverse effects of ACEI/ARB therapy. As kidney disease progresses, treatment discontinuation becomes increasingly common. However, there are conflicting data on the risks versus benefits of ACEI/ARB discontinuation in patients with advanced CKD.
Continuing ACEI/ARB therapy after a decline in eGFR is associated with lower mortality and a lower rate of cardiovascular events, with no increase in kidney failure, the retrospective study suggests. The findings are robust on sensitivity analyses and similar for patients with an eGFR under 30 mL/min/1.73 m2 or a decline of 40% or more. “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,” the investigators conclude [Qiao Y, 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; DOI:10.1001/jamainternmed.2020.0193].
