Feasibility of intracoronary nicorandil for inducing hyperemia on fractional flow reserve measurement: Comparison with intracoronary papaverine

Background: Adenosine and adenosine triphosphate (ATP) are widely used to induce hyperemia for fractional flow reserve (FFR) measurements. Caffeine attenuates their hyperemic effects, but not those of nicorandil and papaverine. No studies have systematically compared the hyperemic efficacies of nicorandil, papaverine, and ATP with and without caffeine abstention.

Methods: FFRs were measured using nicorandil 2 mg (FFR_NC2), nicorandil 4 mg (FFR_NC4), and papaverine (FFR_PAP) in 40 patients (group 1), and using nicorandil 2 mg, ATP (FFR_ATP), ATP plus nicorandil (FFR_ATP+NC2), and papaverine in 20 patients with (group 2) and in 20 patients without caffeine abstention (group 3).

Results: In group 1, FFR_NC2 and FFR_NC4 did not differ (p = 0.321) and were higher than FFR_PAP (p < 0.001 and p = 0.0026). Likewise, FFR_NC2 was higher than FFR_PAP in groups 2 (p = 0.049) and 3 (p < 0.010). In the whole group, Bland-Altman analysis showed a modest mean difference (0.015, p < 0.001) and narrow 95% limits of agreement (-0.025 and 0.056). FFR_NC2 and FFR_PAP strongly correlated (r = 0.975, p < 0.001). Compared with FFR_PAP, FFR_ATP and FFR_ATP+NC2 did not differ in group 2 (p = 1.0 and p = 0.780), but they were higher (p = 0.002 and p = 0.02) in group 3. Adjunctive nicorandil did not decline FFR further in groups 2 (p = 0.942) and 3 (p = 0.294).

Conclusions: Nicorandil 2 mg is a safe and practical alternative for patients who consume caffeine-containing products before the test or have contraindications for adenosine/ATP. Increasing the nicorandil dose to 4 mg or administering adjunctive nicorandil during ATP infusions does not offer any clinical advantages compared with administering nicorandil 2 mg alone.