European and United States regulatory agencies recently issued warnings against the use of dual renin-angiotensin system (RAS) blockade
therapy through the combined use of
angiotensin-converting enzyme inhibitors (ACEIs),
angiotensin II receptor blockers (ARBs) or
aliskiren in any patient, based on absence of benefit for most patients and increased risk of
hyperkalemia,
hypotension, and
renal failure. Special emphasis was made not to use these combinations in patients with
diabetic nephropathy. The door was left open to
therapy individualization, especially for patients with
heart failure, when the combined use of an ARB and ACEI is considered absolutely essential, although renal function,
electrolytes and blood pressure should be closely monitored.
Mineralocorticoid receptor antagonists were not affected by this warning despite increased risk of
hyperkalemia. We now critically review the risks associated with dual RAS blockade and answer the following questions: What safety issues are associated with dual RAS blockade? Can the safety record of dual RAS blockade be improved? Is it worth trying to improve the safety record of dual RAS blockade based on the potential benefits of the combination? Is dual RAS blockade dead? What is the role of
mineralocorticoid antagonists in combination with other RAS blocking agents: RAAS blockade?