Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: A Randomized Clinical Trial

Abstract

Importance: The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown.

Objective: To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG.

Design, setting, and participants: Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017.

Interventions: Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation.

Main outcomes and measures: Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography.

Results: Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with ticagrelor + aspirin; 2 with ticagrelor alone).

Conclusions and relevance: Among patients undergoing elective CABG with saphenous vein grafting, ticagrelor + aspirin significantly increased graft patency after 1 year vs aspirin alone; there was no significant difference between ticagrelor alone and aspirin alone. Further research with more patients is needed to assess comparative bleeding risks.

Trial registration: clinicaltrials.gov Identifier: NCT02201771.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Zhao reported receiving grant funding, personal fees, and nonfinancial support from Medtronic and Johnson & Johnson; grant funding from Novartis; and being an investigator on clinical trials sponsored by Novartis, Sanofi, and Bayer. Dr Zhu reported being an investigator on clinical trials sponsored by and receiving grant funding from Novartis, Sanofi, and Bayer. Dr Xu reported receiving personal fees and nonfinancial support from Medtronic. Dr Cheng reported receiving grant funding and personal fees from Medtronic. Dr Mei has served as a speaker for Medtronic. Dr Chen reported receiving grant funding and personal fees from Johnson & Johnson; grant funding from Bayer; and being an investigator on clinical trials sponsored by Bayer. Dr Wang reported receiving personal fees from Johnson & Johnson.

Figures

Figure 1.. Flow of the Patients Through the Study of Post-CABG Ticagrelor and Aspirin

MSCTA indicates multislice computed tomographic angiography. The primary analysis was conducted on a per-graft basis according to the intention-to-treat principle. aSome patients had multiple reasons.

Figure 2.. Post Hoc Analysis for Ticagrelor + Aspirin vs Aspirin Alone and Ticagrelor Alone vs Aspirin Alone

ACS indicates acute coronary syndrome; SV, saphenous vein. P values were calculated by a generalized equation model. aSYNTAX scores are graded on a continuous scale in which higher scores indicate more complex coronary artery disease.