w w w.c h e s t e r c m s .o r g
Features
Dual RAAS Blockade: Irrational Exuberance Quelled by Clinical Trial Results BY MICHAEL LATTANZIO, DO
R
enin-angiotensin aldosterone system (RAAS) blockade in patients with established heart or kidney disease provides an approximate 20% relative risk reduction in disease progression, cardiovascular, and/or renal endpoints. Many physicians suspected that more complete blockade of the RAAS with the implementation of dual RAAS blockade would confer additive renal and/or cardiovascular benefit. Emerging clinical data has failed to substantiate the cardiovascular and renal benefits of dual RAAS blockade, particularly in individuals with renal disease. Moreover, the use of dual RAAS blockade has been associated with significant safety issues, particularly hyperkalemia, hypotension, and acute renal failure. These findings have dampened the fervor surrounding the use of dual RAAS blockade to achieve superior outcomes over monotherapy. In the ONTARGET trial, the combination of ACE inhibitor and ARB in patients with diabetes or vascular disease failed to show reduction in cardiovascular outcomes, and was associated with increased risk of hypotension, syncope, and renal dysfunction.1 Similarly, the ALTITUDE trial showed no reduction in cardiovascular or renal endpoints among individuals with diabetic kidney disease on dual RAAS blockade.2 This trial was halted due to an increased incidence of hyperkalemia, hypotension, and stroke in the treatment arm. Lastly, the VA NEPHRON-D trial, which examined the effect of ARB plus ACE inhibitor in diabetic nephropathy, demonstrated no renal advantage of dual RAAS blockade over monotherapy. This study also was terminated prematurely due to excess risk of hyperkalemia and renal failure in the treatment arm.3
CHESTER COUNTY
Despite significant excitement regarding the utilization of dual RAAS blockade to achieve superior renal and/or cardiovascular outcomes, emerging data do not support this clinical practice, particularly in renal disease. In individuals with heart failure, the efficacy of dual RAAS blockade to reduce hospitalization is evident, but this will have to be weighed against the potential for safety issues. Further studies are required to determine whether different combinations of the four available RAAS blocking agents available will produce stereotypical results, particularly in individuals with and without renal disease and heart failure. For now, more circumspect use of dual RAAS blockade appears to be warranted. References Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008;372:547-53.
1
Parving HH, Brenner B, McMurray J et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. New England Journal of Medicine 2012;367:2204-2213.
2
Fried LF, Duckworth W, Zhang JH, et al. Design of combination angiotensin receptor blocker and angiotensinconverting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D). Clinical Journal of the American Society of Nephrology: CJASN 2009;4:361-8.
3
Michael Lattanzio, DO, is a clinical nephrologist and hypertension specialist with Clinical Renal Associates of Chester County.
12
MEDICINE