Comparative Effects of Nicorandil, Isosorbide Mononitrate, and Diltiazem on Radial Artery Graft Patency After CABG: Insights from the ASRAB-Pilot Trial

Highlight

• Nicorandil and isosorbide mononitrate treatment post-CABG associated with lower radial artery (RA) graft failure rates than diltiazem at 24 weeks.
• At 1 week post-surgery, nicorandil and isosorbide mononitrate showed trends toward reduced graft failure compared to diltiazem, though differences were not statistically significant.
• This pilot randomized trial provides important comparative data to guide selection of antispastic agents after CABG with RA grafts.
• Larger hypothesis-testing trials are necessary to validate these encouraging findings and inform clinical guidelines.

Study Background and Disease Burden

Coronary artery bypass grafting (CABG) is a well-established surgical intervention for patients with multivessel coronary artery disease, aiming to restore myocardial perfusion. The radial artery (RA) has become a commonly used conduit due to its superior long-term patency compared to saphenous vein grafts. However, RA grafts are susceptible to spasm, which can provoke graft failure and compromise surgical outcomes. Optimal antispastic medication strategies remain controversial, with calcium channel blockers commonly prescribed but with variable effectiveness.

Nicorandil and isosorbide mononitrate, agents with vasodilatory and nitric oxide–donor properties, have been proposed as alternative therapies with potential benefits for RA graft function. Yet, comparative evidence between these agents and established treatments like diltiazem is lacking. This clinical pilot trial (ASRAB-Pilot) addresses this knowledge gap by evaluating the effects of these three drugs on RA graft patency following CABG.

Study Design

ASRAB-Pilot was a single-center, randomized, open-label, parallel-group pilot trial designed to compare oral nicorandil (15 mg daily), isosorbide mononitrate (50 mg daily), and diltiazem (180 mg daily) administered for 24 weeks after CABG using RA grafts.

Eligible patients undergoing RA graft-based CABG were randomized 1:1:1 postoperatively. The primary endpoint was RA graft failure assessed at 1 and 24 weeks by coronary computed tomography angiography (CCTA), classified by the modified Fitzgibbon grading system. Graft failure included grades B (string sign), S (subtotal occlusion), or O (total occlusion).

A total of 150 patients were randomized, with 149 patients and 177 RA grafts evaluable by CCTA. Groups consisted of 50 patients (64 grafts) receiving nicorandil, 50 patients (57 grafts) receiving isosorbide mononitrate, and 49 patients (56 grafts) receiving diltiazem.

Key Findings

At 1 week post-CABG, graft failure rates were:

• Nicorandil: 19.4%
• Isosorbide mononitrate: 18.2%
• Diltiazem: 25.0%

Compared with diltiazem, nicorandil and isosorbide mononitrate showed reduced failure rates (differences of -5.6% and -6.8%, respectively), although confidence intervals crossed zero, indicating statistical non-significance at this early timepoint. Comparing nicorandil to isosorbide mononitrate showed similar rates (difference 1.2%).

At 24 weeks, the graft failure rates were:

• Nicorandil: 16.1%
• Isosorbide mononitrate: 12.5%
• Diltiazem: 27.8%

Here, both nicorandil and isosorbide mononitrate were associated with substantially lower failure rates compared to diltiazem (differences of -11.7% and -15.3%, respectively). Notably, isosorbide mononitrate showed a statistically significant advantage over diltiazem, with the confidence interval marginally excluding zero (-29.8% to -0.2%). Nicorandil had a slightly higher failure rate compared to isosorbide mononitrate (difference 3.6%), without statistical significance.

These results suggest a durable benefit of nicorandil and isosorbide mononitrate over diltiazem in preventing RA graft failure within 6 months post-CABG.

Safety outcomes were not detailed in the summary but are essential for future studies.

Expert Commentary

The ASRAB-Pilot trial provides important preliminary human data supporting the superiority of nicorandil and isosorbide mononitrate over diltiazem for reducing early and midterm RA graft failure. Both nicorandil and isosorbide mononitrate act as vasodilators with nitric oxide–mediated effects, potentially improving endothelial function and limiting RA spasm.

Diltiazem, a calcium channel blocker, has a long clinical history in graft protection but may not optimally address vasomotor tone in all patients. These findings highlight the importance of designing pharmacologic regimens tailored to the distinct physiology of RA grafts.

However, as a pilot trial, this study had a relatively small sample size and was open-label, which may introduce bias. The borderline confidence intervals warrant cautious interpretation. Larger randomized controlled trials with longer follow-up, safety assessments, and functional cardiac outcomes are needed to confirm these findings and potentially update clinical guidelines.

Conclusion

The ASRAB-Pilot trial suggests that nicorandil and isosorbide mononitrate are promising antispastic agents that may reduce radial artery graft failure more effectively than diltiazem following coronary artery bypass graft surgery. Their use could enhance graft patency and improve surgical outcomes. Given the clinical importance of graft preservation for long-term patient survival and quality of life, these findings merit confirmation in large-scale hypothesis-testing trials to refine postoperative management strategies.

References

Zhu Y, Zhang W, Qin K, Liu Y, Yao H, Wang Z, Ye X, Zhou M, Li H, Qiu J, Xu H, Sun Y, Gaudino M, Zhao Q. Effects of Nicorandil, Isosorbide Mononitrate, or Diltiazem on Radial Artery Grafts After CABG: The Randomized ASRAB-Pilot Trial. Circ Cardiovasc Interv. 2025 Apr;18(4):e014542. doi: 10.1161/CIRCINTERVENTIONS.124.014542. Epub 2025 Mar 24. PMID: 40123490.

ClinicalTrials.gov Identifier: NCT04310995