AIM: Dialysis patients might not derive same benefit from ACEIs, ARBs

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Compared with patients with normal kidney function, chronic dialysis patients may not derive the same cardiovascular benefit from angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use, based on a study published April 9 in the Archives of Internal Medicine.

“Routine use of ACEIs and ARBs for the treatment of cardiovascular disease is well established,” according to the study authors. “However, because most randomized controlled trials have excluded patients with advanced chronic kidney disease, the role of ACEIs/ARBs in chronic dialysis patients remains poorly defined.”

Thus, Ravi K. Bajaj, MD, of the Terrence Donnelly Heart Centre at the University of Toronto, and colleagues sought to determine whether ACEI/ARB use is associated with a reduction in mortality and major adverse cardiovascular events in older chronic dialysis patients.

For this analysis, the researchers conducted a retrospective, population-based cohort study using linked healthcare databases in Ontario, Canada. To minimize bias, they used a new-user study design. The study population was composed of older chronic dialysis patients in Ontario (older than 66 years) who were newly treated with ACEIs/ARBs, calcium channel blockers (CCBs) or statins between July 1, 1991, and July 31, 2007.

Then, they selected new treatment with ACEIs/ARBs as the exposure group and treatment with CCBs or statins only as the comparator groups to minimize confounding by indication and because CCBs and statins have not been shown to be clearly beneficial in this population. They also excluded patients with missing demographic information or incomplete drug records.

Patients were stratified into one of three mutually exclusive treatment groups (ACEI/ARB, CCB or statin) and were prospectively observed for up to five years, or March 31, 2010. The pre-specified primary endpoint was a composite of all-cause mortality or hospitalization for MI, stroke, heart failure (HF) or coronary revascularization. Secondary endpoints included each component of the primary endpoint.  

During the study period, Bajaj et al identified 1,950 older chronic dialysis patients in Ontario who initiated treatment with one of the study drug classes. There were no systematic differences in the baseline characteristics between the treatment groups, and there was no significant difference in event-free survival among the three groups.

In multivariable analysis, the use of ACEIs/ARBs was not independently associated with a reduction in the primary endpoint or secondary endpoints compared with the CCB group. They also obtained similar results when the ACEI/ARB group was compared with the statin-only group.

In this population-based cohort study of chronic dialysis patients older than 65 years, the researchers found that new use of ACEIs or ARBs was not independently associated with an overall reduction in major adverse cardiovascular events.

“Data from previous randomized controlled trials and observational studies have been conflicting. This study offers unique insights into the use of ACEIs/ARBs in chronic dialysis patients through its new-user study design,” the study authors wrote. “Although this new-user study design has not been used extensively in chronic dialysis patients, it allows for a less biased evaluation of the 'real world' safety and effectiveness of secondary prevention therapies in such patients, in contrast to randomized controlled trials, which often recruit highly selected healthier patients.”

However, the researchers acknowledged some limitations, including that drug therapy was not randomly assigned, they analyzed classes of drugs rather than individual drugs and selected control groups with the expectation that these would serve as non-active comparators.  

Given “the substantial cardiovascular morbidity and mortality in the expanding chronic dialysis patient population,” Bajaj and colleagues suggested that a large definitive randomized controlled trial of ACEIs/ARBs is warranted.