According to the results of a study reanalyzing data obtained from an FDA review of the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes (MERLIN) trial, ranolazine potentiates the effects associated with ACE inhibitors (ACEIs), as well as angiotensin receptor blockers (ARBs).
In the MERLIN trial, 6560 acute coronary syndrome patients were randomized to receive either ranolazine or placebo and were monitored for a median time of 348 days; during the trial, 78% of the patients received an ACEI or an ARB.
“Rates of [ACEI] or [ARB]-related adverse events (angioedema, dry cough, renal impairment, hypotension, anemia, and serum potassium >5.5mmol/L) were higher in patients receiving ranolazine and an ACEI or ARB,” the study authors stated. They added, “The 3 adverse events that ACEI/ARBs should mitigate (hypokalemia, hypertension, and serum potassium level <3.5mmol/L) were lower in patients receiving ranolazine (although hypertension and serum potassium level <3.5mmol/L were lower with ranolazine regardless of ACEI/ARB use).”
From these findings, the study authors determined that potentiation of ACEI and ARB adverse effects was caused by an interaction with ranolazine. Although the exact mechanism of this interaction is unknown, they determined that it is clinically relevant and may actually be beneficial in some patients such as those with hypertension or heart failure. The study authors also highlighted the importance of healthcare providers recognizing this interaction, as well as monitoring for and making dose modifications if necessary, for patients receiving ACEI/ARB therapy and ranolazine.
T.A. Marciniak and V. Serebruany, Ranolazine, ACE Inhibitors, and Angiotensin Receptor Blockers, The American Journal of Medicine, https://doi.org/10.1016/j.amjmed.2019.02.032