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Ranolazine may have a role in elective PCI, pilot study hints

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Treatment with the antianginal drug ranolazine before elective percutaneous coronary intervention (PCI) significantly reduced procedure-related myocardial injury in a small pilot study from Italy.

“Ranolazine has very few side effects and contraindications, so it would be an excellent additional drug in this setting,” study co-chairman Dr. Francesco Pelliccia from La Sapienza University in Rome noted in an email to Reuters Health.

Ranolazine, approved in the United States in 2006 for treatment of stable angina pectoris, has a unique mechanism of action, the study team notes in a paper online now in the American Heart Journal. The drug blocks the inward sodium channel current and prevents the increase in intracellular calcium concentrations that occurs through the sodium-calcium exchanger in case of myocardial ischemia.

“Our finding that the extent of PCI-induced myocardial injury was significantly reduced if ranolazine was administered before PCI is consistent with the experimental observation that preventing calcium accumulation in case of myocardial ischemia can limit myocardial infarction,” the investigators say.

The drug also appears to have other pleiotropic nonanginal effects including improvement in endothelial function coupled with a decrease in inflammatory status, as well as reduction in coronary vascular resistance through alpha-1 adrenergic blockade, which might contribute to decrease myocardial necrosis due to procedural microembolization during PCI.

Dr. Pelliccia and colleagues enrolled in their study 70 patients (mean age 62, 42 men) with stable angina and similar clinical characteristics who were scheduled for elective PCI. For one week before the procedure, half took ranolazine (1,000 mg twice daily) and half took placebo. Creatine kinase-MB, troponin I, and myoglobin levels were measured at baseline and at eight and 24 hours after PCI.

The researchers report that periprocedural MI – defined as a CK-MB rise greater than or equal to three times above the upper limit of normal (primary – occurred less often following PCI in the ranolazine group (2 patients, 6%) than the placebo group (8 patients, 22%). The odds ratio was 0.25 (p=0.41).

Fewer patients in the ranolazine arm had any post-PCI elevation (greater than one times above the upper limit of normal) in CK-MB (23% vs 40%; p=0.010), troponin I (31% vs 48%; p=0.11), and myoglobin (28% vs 43%; p=0.033).

Before PCI, levels of the three markers were similar and within normal limits, whereas post-PCI peak values of all markers were significantly lower in patients pre-treated with ranolazine than in those given placebo (CK-MB: 3.1 vs 7.7 ng/mL, p

At 30 days, major adverse cardiac events (MACE), including death, MI and target vessel revascularization) occurred in three patients in the ranolazine group (9%) vs 10 (28%) in the placebo group. When periprocedural MI was omitted, 30-day MACE rates were similar in the two groups (3% vs 6%; p=0.1).

“Our study has shown that pretreatment with ranolazine may reduce ischemic complications during coronary angioplasty, possibly due to its antiischemic effects,” Dr. Pelliccia told Reuters Health.

“However, our study is preliminary and included a limited number of patients, so we believe it is too early for ranolazine to be added to the standard treatment before coronary angioplasty. Since a pretreatment with ranolazine is at low cost and has no risk, clinicians may consider use of ranolazine in selected cases or enroll the patient in new larger clinical trials (which we hope will be forthcoming),” Dr. Pelliccia said.

The authors have stated that they have no conflicts of interest.

SOURCE:

A pilot randomized study of ranolazine for reduction of myocardial damage during elective percutaneous coronary intervention

Am Heart J 2012.