Nicorandil Matches Safety, Efficacy of Adenosine in FFR Assessment

Nicorandil, a vasodilator, appears to effectively induce hyperemia during fractional flow reserve (FFR) measurement with few adverse events. The drug may prove to be a more convenient, safer alternative to adenosine, according to a paper published online February 8, 2013, ahead of print in the European Heart Journal.

Bon-Kwon Koo, MD, PhD, of Seoul National University Hospital (Seoul, South Korea), and colleagues studied 194 patients with intermediate lesions on angiography (40-70% occlusion on visual estimation) who underwent FFR assessment. They evaluated different methods of achieving maximal hyperemia in each patient, including:

• Intracoronary bolus injection of adenosine (80 µg in the LCA, 40 µg in the RCA)
• IV infusion of adenosine (140 µg/kg/min)
• Intracoronary bolus injection of nicorandil (1 mg)
• Intracoronary bolus injection of nicorandil (2 mg)

Fewer Side Effects with Novel Drug

In terms of hyperemic efficacy, intracoronary nicorandil 2 mg was noninferior to IV adenosine (FFR 0.82 ± 0.09 vs. 0.82 ± 0.10; P for noninferiority < 0.001) and superior to the 1-mg nicorandil dose (FFR 0.84 ± 0.09; P < 0.001). A strong correlation existed between FFR values obtained with nicorandil 2 mg and IV adenosine (R² = 0.934). The higher nicorandil dose also was more effective than intracoronary adenosine (P < 0.001).

Moreover, the proportion of patients with functionally significant stenoses was similar between nicorandil 2 mg and IV adenosine, amounting to 19.1% and 20.6% using an FFR threshold of 0.75 (P = 0.453) and 34.5% and 30.9% when the FFR cut-off value was set at 0.80 (P = 0.210).

Atrioventricular block occurred in 12 patients during adenosine injection, 4 patients given IV adenosine, and none receiving nicorandil. Patient-reported chest pain also was less severe with nicorandil than with IV adenosine (P < 0.001).

A subgroup of 70 patients underwent additional analyses. Median values for index of microcirculatory resistance (IMR) in this group were similar between nicorandil 2 mg and IV adenosine at 14.5 (interquartile range [IQR], 11.7-20.7) and 16.7 (IQR, 13.0-20.0). Patients receiving nicorandil experienced fewer hemodynamic changes (table 1).

Table 1. Hemodynamic Changes vs. Baseline: Median (IQR)

“This study suggests that an [intracoronary] bolus injection of nicorandil is a simple, safe, and effective way to induce steady-state hyperemia for invasive physiological evaluations in patients undergoing angiography in a cardiac catheterization laboratory,” the investigators conclude. “The use of this novel agent may encourage interventional cardiologists to perform FFR measurement in their patients to optimize interventional procedures.”

Known drawbacks to IV adenosine, they say, are the need for additional venous access and complications including chest discomfort, bronchial hyper-reactivity, and atrioventricular conduction delay.

For Now, Access Is Limited

However, while nicorandil is approved for the treatment of angina in several European and Asian countries, the drug is not currently available in the United States.

William F. Fearon, MD, of Stanford University Medical Center (Stanford, CA), told TCTMD in an e-mail communication that the current paper is his first encounter with the drug. Dr. Fearon served as co-principal investigator of the FAME trial, which showed that in patients with multivessel disease undergoing PCI, FFR guidance offers better outcomes than angiography alone.

In an e-mail communication, Dr. Koo pointed out that “this situation may well change in the near future.” Not only have the safety and cardioprotective effect of intracoronary administration of nicorandil been shown by several studies, he said, there is also evidence that the drug may benefit patients with acute MI or slow flow after PCI.

Drugs Have Pros and Cons

Both Drs. Koo and Fearon cited nicorandil’s short plateau time, amounting to 26.1 ± 10.4 seconds, as its major weakness. “This is adequate for performing a slow pullback of the pressure wire to interrogate the entire vessel, but not ideal,” Dr. Fearon said, while Dr. Koo noted that less experienced operators may not have time to measure IMR.

The biggest issue with IV adenosine, is its “inconvenience,” Dr. Koo said. “Most of the complications associated with adenosine are transient and minor.”

There are “certainly drawbacks” to adenosine, Dr. Fearon agreed, noting that its current position as gold standard mainly stems from the fact that “the large clinical trials validating FFR in various settings used intravenous adenosine as the hyperemic agent.” But based on the current findings, “nicorandil may be a viable alternative for inducing hyperemia in order to measure FFR,” he concluded.

Another option being explored is regadenoson, a vasodilator. “Moreover, there have been active investigations on novel physiologic indices that do not require hyperemia,” Dr. Koo added, noting that all of these adenosine replacements “still require further investigation to be adapted in routine clinical practice.”

 

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Source:
Jang H-J, Koo B-K, Lee H-S, et al. Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory. Eur Heart J. 2013;Epub ahead of print.

 

 

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