http://www.medpagetoday.com/Cardiology/Hypertension/43052?xid=nl_mpt_DHE_2013-11-22

Cardiovascular

ACE Inhibitors Cut Mortality in Renal Patients

Published: Nov 21, 2013

By Cole Petrochko, Staff Writer, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

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Chronic kidney disease patients who did not depend on dialysis were significantly less likely to die during the study period if they received angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), researchers found.

Among older patients with nondialysis chronic kidney disease who had never taken ACE inhibitors and AR blockers, administration of either agent was associated with a 19% lower hazard of death (95% CI 0.78-0.84, P<0.001) in an intention-to-treat analysis, according toCsaba Kovesdy, MD, of the Memphis Veterans Affairs Medical Center in Tennessee, and colleagues.

Subgroup analysis also showed that the association with lower risk of mortality was significant across all subgroups, they wrote online in the Journal of the American College of Cardiology.

Recent research has shown that dual treatment with ARBs and ACE inhibitors has been associated with acute kidney injury and hyperkalemia when compared with monotherapy, and that increased prescription rates for either drug class has been tied to increased risks for renal injuries. However, links between ARBs and myocardial infarction have been dispelled.

The authors conducted an analysis of mortality risk with use of ARBs and ACE inhibitors in a population of 40,494 U.S. veterans with chronic kidney disease that did not require dialysis and who had no prior exposure to treatment with either drug class.

They noted that prior research has been inconclusive, and that much of it has been "limited to patients with certain comorbid characteristics."

Participants' glomerular filtration rate (GFR) was estimated through measurement of serum creatinine and demographic characteristics based on the Chronic Kidney Disease Epidemiology Collaboration equation. This was used to establish the presence of chronic kidney disease, which they defined as a stable estimated GFR of less than 60 mL/min/1.73 m² or a stable GFR of 60 or more mL/min/1.73 m² and elevated urinary microalbumin.

Researchers recorded whether participants received ACE inhibitors or ARBs within 1 year after entering the cohort (n=20,247) or if they were untreated during the study (n=20,247).

Patient demographic information was available through the Veterans Affairs Corporate Data Warehouse, which included age, sex, race, and blood pressure, the latter of which was gathered from October 2004 to October 2009. Patients' comorbidities were recorded in the Veterans Affairs Inpatient and Outpatient Medical SAS Datasets, and included coronary artery disease, angina, myocardial infarction, percutaneous coronary intervention receipt, and receipt of coronary artery bypass grafting.

All-cause mortality was reported through a Veterans Affairs registry of death dates or date of last medical or administrative encounter.

Associations between drug treatment and risk for mortality were measured in intention-to-treat and as-treated models, the latter of which allowed patients "to switch treatment groups in time-dependent analyses according to actual subsequent exposure status."

Patients were analyzed in subgroups categorized by sociodemographic characteristics, presence or absence of comorbid conditions, and laboratory and blood pressure variables.

Participants had a mean baseline age of 74.8; 89% were white, 8% were black. Roughly one quarter had diabetes (22%) and they had a mean eGFR of 50 mL/min/1.73 m².

Patients who received drug treatment were younger, more likely to be black, and were more likely to have diabetes, hypertension, congestive heart failure, and cardiovascular disease. They also had a higher eGFR.

Over a median 4.7 years of follow-up, there were 5,028 deaths in the treatment group versus 6,450 deaths in the untreated group. Most patients received their medication more than half of the time during follow-up (66%), though only 8.4% received their medication 100% of the time during follow-up.

In the as-treated analysis, receipt of ACE inhibitor or ARB was associated with a 63% reduced odds of mortality (95% 0.34-0.41).

The authors noted that uncertainty about the effects of these drugs in non-dialysis dependent patients with chronic kidney disease "stems from the paucity of clinical trials with a mortality end-point in this patient population," such as those with renal end points or with the exclusion of patients with moderate or advanced disease.

Potential mechanisms of effect for this relationship may include decrease of severity of left ventricular hypertrophy, dilation, remodeling, and heart failure with treatment, as well as renoprotection offered by the drugs.

They noted that these data may not generalize to patients outside of the Veterans Affairs system. Their study was also limited by lack of data on end stage renal disease or hospitalizations, lack of data on cause of death, absent information on smoking status, and lack of comparison or measurement of effects of other antihypertensive agents.

The study was supported by the Department of Veterans Affairs.

The authors declared that they had no conflicts of interest