ACE inhibitors, ARBs linked to reduced mortality, elevated renal-related hospitalization after AKI
The use of ACE* inhibitors or ARBs** within 6 months of hospital discharge following an episode of acute kidney injury (AKI) may reduce mortality, according to a retrospective cohort study from Canada, though these medications may be associated with an elevated risk of renal-related hospitalization.
“[P]atients with AKI may benefit from ACE inhibitor or ARB therapy after discharge, an intervention that does not require specialized care and could be readily implemented with appropriate monitoring,” said the researchers.
They identified 46,253 adults from the Alberta Kidney Disease Network (mean age 68.6 years, 52.8 percent male) who experienced AKI while hospitalized (≥50 percent increase in serum creatinine concentration, ≥0.3 mg/dL increase within 48 hours, and/or need for dialysis during hospitalization), 48 percent of whom were using ACE inhibitors or ARBs within 6 months following hospital discharge. About 54.5 percent were using ACE inhibitors or ARBs within 6 months prehospitalization and 13.4 percent did not continue these medications post-discharge. The final study cohort comprised 18,912 patients (matched users and nonusers).
Approximately half of the patients (n=23,407) had a history of chronic kidney disease prior to hospitalization, while 75.9, 29.2, and 20.9 percent had hypertension, chronic heart failure, and a history of stroke or transient ischaemic attack, respectively.
After 2 years, patients with AKI who used ACE inhibitors or ARBs within 6 months post-discharge had a lower mortality rate compared with nonusers (adjusted hazard ratio [adjHR], 0.85). [JAMA Intern Med 2018;doi:10.1001/jamainternmed.2018.4749]
This reduction was demonstrated regardless of whether patients were new users of (new prescription within 6 months post-discharge and no use 6 months prior to hospitalization; adjHR, 0.85) or continued users (prescriptions both 6 months before and after hospitalization; adjHR, 0.77), though compared with nonusers, mortality rate was higher among patients who discontinued ACE inhibitors or ARBs which were prescribed pre-hospitalization (adjHR, 1.23). A higher mortality rate was also noted when ACE inhibitors or ARBs were started within 90 days of hospital discharge vs after 90 days (adjHR, 1.15).
Conversely, patients taking ACE inhibitors or ARBs after discharge had an elevated risk of hospitalization for renal causes (adjHR, 1.28), with the main causes being acute renal failure, congestive heart failure, and hyperkalaemia.
Use of ACE inhibitors or ARBs after discharge had no bearing on risk of progression to end-stage renal disease.
ACE inhibitor or ARB users with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 derived a lower survival benefit compared with those with an eGFR ≥60 mL/min/1.73 m2 (HR, 0.89 vs 0.81; p=0.03), as did ACE inhibitor users without hypertension compared with those with hypertension (HR, 1.10 vs 0.84; p=0.001).
Pros and cons of RAS*** blocker use in AKI
“These findings suggest that there is an opportunity to improve post-discharge care in patients with AKI,” said the researchers. However, the elevated risk in renal-related hospitalizations calls for close monitoring of patients with AKI who take these medications, with potential adjustment of drug regimens.
With previous studies demonstrating a link between ACE inhibitor or ARB use and a mortality risk reduction among patients with cardiovascular disease, [N Engl J Med 1995;333:1670-1676; N Engl J Med 2003;349:1893-1906] the researchers postulated that the mortality risk reduction in this study may have been “secondary to a reduction in cardiovascular events”, seeing as how a large number of patients had pre-existing cardiovascular risk factors.
They acknowledged the limitations that are commonplace with a retrospective, observational study as well as the lack of information on treatment adherence or if access to medications was suggestive of better access to care.
According to Professors Robert Alpern and Aldo Peixoto from the Yale University School of Medicine, New Haven, Connecticut, US, some questions remain regarding the use of these medications in AKI.
“The frequent association between exposure to RAS blockers and the development of new AKI and concerns about altered renal haemodynamics have made it standard practice that use of RAS blockers be stopped in the context of AKI. However, experimental evidence suggests that renal blood flow may be improved with these agents in AKI because of ischaemia reperfusion,” they said. [JAMA Intern Med 2018;doi:10.1001/jamainternmed.2018.4757]
There is also the question of whether the mechanism of action differences between ACE inhibitors and ARBs would affect outcomes in AKI, and whether there is a renal function threshold below which RAS blockers would not be used, they said.