Ranolazine (Ranexa) has no role in Acute Coronary Syndrome (ACS) cases

Hello All!
I am lagging behind updating this blog with several important clinical trial updates¹ recently presented at American College of Cardiology's 56th annual scientific session (ACC.07) and Innovation in Intervention: i2 Summit 2007 (see reference for official outline links)
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ACC.07 update (March 27, 2007): Ranolazine (Ranexa) has no role in Acute Coronary Syndrome (ACS) cases | MERLIN TIMI-36 results
Ranolazine (Ranexa)² is a new class of anti-anginal drug, approved by FDA³ in January 2006 for the treatment of chronic angina patients who have failed to other forms of angina treatments (long-acting nitrates, calcium channel blockers and beta blockers). This indication was based on initial clinical trials, namely ERICA⁴ (Efficacy of Ranolazine in Chronic Angina) and CARISA⁴ (Combination Assessment of Ranolazine In Stable Angina) involving more than 1300 patients. Studies found prolong QT interval as a adverse reaction which might lead to proarrythmic effects and hence, drug is restricted for use in chronic angina patients as a second-line option.

The new trial named, MERLIN TIMI-36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes)⁴ was started in May 2006 which was a multi-national, double-blind, randomized, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of Ranexa during acute and long-term treatment in approximately 6,500 patients with non-ST elevation ACS treated with standard therapy. The primary efficacy endpoint in MERLIN TIMI-36 is time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction or recurrent ischemia in patients with non-ST elevation ACS receiving standard therapy. The study was also evaluating the safety of long-term treatment with Ranexa compared to placebo.⁵ Results of MERLIN TIMI-36 were presented at ACC.07 which showed no role of Ranolazine in management of patient with ACS and also it has not disease-modifying effects in stable angina patients. However, trial showed no adverse effects of drug in terms of arrhythmia and increase mortality because of its prolong QT interval side-effect and suggested that it might have antiarrhytmic effects.

Effect of Ranolazine in preventing recurrent angia is supported by all major clinical trials. It is a unique agent that, unlike other classes of anti-anginal therapy, does not significantly reduce heart rate or blood pressure. As MERLIN study has shown better safety profile of Ranolazine, it is likely that Ranolazine will gain one more indication as a first-line therapy in stable angina patients in coming years.⁶ Precise mechanism of action of Ranolazine is unclear but it is believed to be a selective inhibitor of the late sodium current relative to peak sodium channel current, and via this mechanism, it may decrease sodium-dependent intracellular calcium overload during ischemia and reperfusion.⁷

Reference:
1. ACC.07 | i2 Summit 2007 : Official Text and Multimedia Resources | MERLIN TIMI-36 outline
2. Ranolazine (Ranexa)^® prescribing information from CV Therapeutics
3. FDA approval of Ranolazine: January 31, 2006
4. Clinical trial summary from ACC: CARISA | ERICA | MERLIN TIMI-36 (May require ACC account access)
5. CV Therapeutics article, dated 9 July 2006 - medicalnewstoday.com
6. MERLIN: No Role for Ranolazine in ACS but First-Line Indication in Stable Angina Now Likely - Heartwire (WebMD) news
7. Hale SL, Kloner RA | Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit | J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55 | PMID: 17220471
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