MERLIN: Ranolazine associated with antiarrhythmic effect

In a prespecified secondary analysis of the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial, ranolazine was associated with a reduction in the number of episodes of ventricular tachycardia and supraventricular tachycardia. The results of the analysis were presented at the European Society of Cardiology Congress 2007 in Vienna, Austria.

Key Points

In a prespecified secondary analysis of the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial, ranolazine was associated with a reduction in the number of episodes of ventricular tachycardia and supraventricular tachycardia. The results of the analysis were presented at the European Society of Cardiology Congress 2007 in Vienna, Austria.

The intravenous (IV) formulation of ranolazine, which was used in this trial, is pending FDA approval.

Because of previously observed prolongation of the QT interval in patients treated with approved dosages of ranolazine, patients enrolled in the MERLIN trial received continuous 7-day Holter monitoring to assess the incidence of clinically significant arrhythmias.

Prolongation of the QT interval with ranolazine "ranges from 2 to 6 msec, and this does raise the theoretical risk of ventricular tachycardia," said Benjamin M. Scirica, MD, MPH, a cardiologist at Brigham and Women's Hospital, Boston, Massachusetts.

In subgroup analyses, the use of ranolazine was associated with a consistent antiarrythmic effect in patients with depressed left ventricular function and prior episodes of heart failure.

"This is the first clinical report of the antiarrhythmic effects of ranolazine and [it] supports the antiarrhythmic findings that have been demonstrated in animal models," Dr Scirica said.

According to A.J. Camm, MD, chair of clinical cardiology, St George's Hospital Medical School, London, UK, "There remains a regulatory concern about small degrees of QT prolongation since very small incidences of torsades de pointes are seen with these [anti-arrhythmic] drugs."

Dr Camm said the mechanism of the effect of ranolazine is not clear. "It may be primarily anti-ischemic, or it may be more related to a specific antiarrhythmic effect because of inhibition of the slow sodium current."

Dr Scirica said that, as a result of the new analysis, studies designed specifically to address the potential role of ranolazine as an antiarrhythmic agent are warranted.