Ranolazine, ACE Inhibitors, and Angiotensin Receptor Blockers.

Background: Ranolazine is an anti-angina agent with many metabolites creating the potential for off-target effects. The U.S. Food and Drug Administration (FDA) reviews sometimes contain clinically relevant data not found in other sources.

Methods: We reanalyzed data in an FDA review of the placebo-controlled MERLIN trial of ranolazine to display differences in adverse event rates graphically.

Results: Rates of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)-related adverse events (eg, angioedema, dry cough, renal impairment, hypotension, anemia, and serum potassium > 5.5 mmol/L) were higher in patients receiving ranolazine and an ACEI or ARB. Rates of adverse events that should be decreased by ACEI/ARBs (eg, hypokalemia, hypertension, and serum potassium < 3.5 mmol/L) were lower in patients receiving ranolazine and an ACEI or ARB compared to rates in patients receiving placebo and an ACEI or ARB.

Conclusions: Ranolazine potentiates the effects of ACEIs and ARBs. Clinicians should monitor for this potentiation when initiating treatment with ranolazine and an ACEI or ARB.