Description
Dual RAAS blockade with ACE inhibitors and ARBs provides no additional cardiovascular benefit over either agent alone and significantly increases the risk of hypotension, hyperkalemia, and acute kidney injury.
Mechanism
Both drugs block angiotensin II effects (ACEi prevents its synthesis; ARB blocks AT1 receptors); combination results in excessive RAAS inhibition, causing additive hypotension, reduced aldosterone (hyperkalemia), and impaired renal autoregulation.
Clinical Significance
ONTARGET trial demonstrated no cardiovascular benefit with dual blockade but significantly higher rates of hypotension (4.8%), syncope, diarrhea, renal impairment, and hyperkalemia.
Management
Avoid dual RAAS blockade in most patients. Exception: select cases of refractory heart failure under specialist supervision with close monitoring of BP, renal function, and potassium.