Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis

Sigrid Sandner, Björn Redfors, Dominick J. Angiolillo, et al

JAMA. 2022;328(6):554-562. doi:10.1001/jama.2022.11966

Key Points

Question Is ticagrelor dual antiplatelet therapy (DAPT) for patients undergoing coronary artery bypass graft surgery associated with differences in vein graft failure and bleeding events compared with aspirin?

Findings In this individual patient data meta-analysis that included 4 randomized clinical trials, 1316 patients and 1668 vein grafts, ticagrelor DAPT compared with aspirin was associated with a significantly lower incidence of vein graft failure (11.2% vs 20.0%) and a significantly higher incidence of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events (22.1% vs 8.7%).

Meaning In patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure, as well as a significantly increased risk of clinically important bleeding.

Abstract

Importance The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear.

Objective To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery.

Data Sources MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction.

Study Selection Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure.

Data Extraction and Synthesis Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used.

Main Outcomes and Measures The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin.

Results A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, −8.7% [95% CI, −13.5% to −3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, −9.7% [95% CI, −14.9% to −4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, −1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, −2.6% [95% CI, −9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, −2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46).

Conclusions and Relevance Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.