Antianginal Drug May Reduce Periprocedural MI in Elective PCI

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For patients undergoing elective percutaneous coronary intervention (PCI), pretreatment with the antianginal agent ranolazine substantially reduces the risk of periprocedural myocardial infarction (MI), according to a small randomized study published online May 23, 2012, ahead of print in the American Heart Journal.

Ranolazine (Ranexa; Gilead Sciences, Foster City, CA) was approved by the US Food and Drug Administration for the treatment of chronic angina in 2006. During ischemia, the drug lessens intracellular sodium and calcium accumulation, thus possibly limiting myocardial damage.

Francesco Pelliccia, MD, PhD, of Sapienza University of Rome (Rome, Italy), and colleagues randomized patients slated for PCI at 2 institutions to receive either ranolazine (1,000 mg twice daily; n = 35) or placebo (n = 35) for 7 days prior to the intervention. CK-MB and troponin I levels were measured at baseline and at 8 and 24 hours after PCI.

Periprocedural MI, defined as a postprocedural increase of CK-MB at least 3 times the upper limit of normal (ULN), was 75% less likely in conjunction with ranolazine (OR 0.25; 95% CI 0.05-0.95). The placebo group also had higher rates of periprocedural myocardial injury, defined as any post-PCI biomarker increase above the ULN (table 1).

Table 1. Periprocedural Outcomes

Baseline biomarker levels were similar and within normal limits in the 2 groups, whereas post-PCI peak values were lower in patients treated with ranolazine than in those given placebo for both CK-MB (3.1 ± 15.0 ng/mL vs. 7.7 ± 19.1 ng/mL; P < 0.05) and troponin I (0.15 ± 0.35 vs. 0.47 ± 0.49 ng/mL; P < 0.05). Myoglobin measurements from before and after the intervention followed a similar pattern.

Adverse events at 30 days were similar between the 2 groups when periprocedural MIs were not considered (3% with ranolazine vs. 6% with placebo).

‘Unique Mechanism’ Makes the Difference

“The results of our investigation support the hypothesis that ranolazine may offer a protection to cardiac myocytes from ischemic injury,” the authors write, explaining that the drug “has a unique mechanism of action because it 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.”

In addition, they note, ranolazine “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 α(1)-adrenergic blockade, which might contribute to decrease[d] myocardial necrosis due to procedural microembolization in the setting of PCI.”

However, because of the small size of the study, Dr. Pelliccia and colleagues conclude that the findings should only be considered “hypothesis generating” and need confirmation.

Larger Patient Population Needed

In an interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), was unsure whether or not ranolazine has much potential in this patient group because “it’s not the first kind of drug that [has been] looked at.” Even after a series of trials showed that statins might prevent periprocedural MI, their use in the preprocedural setting has not increased, he noted.

“Usually people go home on statins, but they are not pretreated if they are not known to have coronary disease,” he continued. “We know that thienopyridines may prevent periprocedural myocardial infarction and yet in the elective setting, patients are not usually preloaded. So I don’t expect that [ranolazine] will necessarily go into major use, but certainly it’s another piece of evidence that shows we can do something about periprocedural myocardial infarction.”

Regardless, Dr. Brener agreed with the authors that ranolazine should be tested in a bigger population. RIVER-PCI is currently testing the drug against placebo in more than 2,500 patients with incomplete revascularization after PCI. He reported that the results will not be available until at least the end of 2014.

Study Details

The ranolazine and placebo groups were similar with regard to age, sex, cardiovascular risk factors, clinical presentation, left ventricular function, renal function, and medical therapy at the time of the procedure. Coronary anatomy and lesion type were also similar between the 2 groups.

Pelliccia F, Pasceri V, Marazzi G, et al. A pilot randomized study of ranolazine for reduction of myocardial damage during elective percutaneous coronary intervention. Am Heart J. 2012;Epub ahead of print.

Related Stories:

• Study Proposes New CK-MB Threshold for Periprocedural MI
• CK-MB More Accurate Than Troponin in Identifying Post-PCI MI
• Periprocedural MI Does Not Predict Long-Term Mortality

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