DAPT vs. aspirin after CABG: less vein graft failures, more bleeding
Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis
Literature - Sandner S, Redfors B, Angiolillo DJ, et al. - JAMA. 2022 Aug 9;328(6):554-562. doi: 10.1001/jama.2022.11966Introduction and methods
Background
Of alle saphenous vein grafts placed, 10%–25% occlude within the first year after surgery [1,2], mainly due to thrombosis [2,3]. Although dual antiplatelet therapy (DAPT ) is the guideline-recommended therapy after percutaneous coronary revascularization [4], there is considerable controversy regarding the benefit of DAPT after CABG surgery.
Aim of the study
The authors aimed to compare the effects of ticagrelor DAPT with aspirin alone on saphenous vein graft failure and bleeding events after CABG surgery.
Methods
In this systematic review and meta-analysis, 4 RCTs comparing the effects of ticagrelor DAPT or ticagrelor monotherapy versus aspirin on failure of saphenous vein grafts (n=1668 in total) in 1316 patients undergoing CABG surgery who had follow-up for graft imaging were selected from the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Individual patient data were collected from the principal investigators of the eligible trials.
Outcomes
In the primary analysis, the incidence of saphenous vein graft failure per graft—defined as saphenous vein graft occlusion or stenosis >50%—was the primary outcome. Secondary outcomes were the incidences of saphenous vein graft failure per patient, Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events, composite outcome of saphenous vein graft failure or CV death, and major adverse cardiac and cerebrovascular events (MACCE ).
A supplementary analysis for the primary outcome included RCTs comparing ticagrelor monotherapy with aspirin.
Main results
Ticagrelor DAPT versus aspirin
- In the primary analysis (n=871 patients), the primary outcome of graft failure occurred in 11.2% (54/481) of saphenous vein grafts in the ticagrelor DAPT group and in 20% (99/494) of those in the aspirin group (difference: –8.7%; 95%CI: –13.5% to –3.9%; odds ratio (OR): 0.51; 95%CI: 0.35–0.74; P<0.001).
- When assessed per patient (secondary outcome), the incidence of saphenous vein graft failure was 13.2% (52/394 patients) in the ticagrelor DAPT group and 23.0% (92/400 patients) in the aspirin group (difference: –9.7%; 95%CI: –14.9% to –4.4%; OR: 0.51; 95%CI: 0.35–0.74; P<0.001 ).
- The association of ticagrelor DAPT with saphenous vein graft failure risk was consistent across all prespecified subgroups (f.e., aged >65 vs. ≤65 years, women vs. men, and smokers vs. nonsmokers).
- Ticagrelor DAPT was significantly associated with a higher incidence of BARC type 2, 3, or 5 bleeding events compared with aspirin (22.1% vs. 8.7%; difference: 13.3%; 95%CI: 8.6%–18.0%; OR: 2.98; 95%CI: 1.99–4.47; P<0.001) and a lower risk of the composite of saphenous vein graft failure or CV death (13.9% vs. 23.4%: difference: −9.4%; 95%CI: −14.7% to −4.1%; OR: 0.52; 95%CI: 0.36–0.76; P<0.001) but not with a lower MACCE risk (6.7% vs. 5.5%; difference: 1.2%; 95%CI: −2.0% to 4.3%; hazard ratio: 1.21; 95%CI: 0.70–2.08; P=0.50).
Ticagrelor monotherapy versus aspirin
- Ticagrelor monotherapy was not significantly associated with saphenous vein graft failure compared with aspirin per graft (19.3% vs. 21.7%; difference: –2.6%; 95%CI: –9.1% to 3.9%; OR: 0.86; 95%CI: 0.58–1.27; P=0.44) or per patient (25.2% vs. 29.3%; difference: −4.1%; 95%CI: −11.9% to 3.7%; OR: 0.81; 95%CI: 0.55–1.20; P=0.30).
- There was also no significant association between ticagrelor monotherapy and BARC type 2, 3, or 5 bleeding events compared with aspirin (8.9% vs. 7.3%; difference: 1.7%; 95%CI: –2.8% to 6.1%; OR: 1.25; 95%CI: 0.69–2.29; P=0.46).
Conclusion
In patients undergoing CABG surgery, ticagrelor DAPT was associated with a decreased risk of saphenous vein graft failure compared with aspirin alone. However, this was accompanied by an elevated risk of clinically important bleeding. According to the authors, their study results imply “that a patient’s individual risk of graft failure, ischemic events, and bleeding needs to be weighed carefully when deciding whether to add ticagrelor to aspirin after CABG surgery.”
References
1. Antonopoulos AS, Odutayo A, Oikonomou EK, et al; SAFINOUS-CABG (Saphenous Vein Graft Failure—An Outcomes Study in Coronary Artery Bypass Grafting) group. Development of a risk score for early saphenous vein graft failure: an individual patient data meta-analysis. J Thorac Cardiovasc Surg. 2020;160(1):116-127.e4.
2. Xenogiannis I, Zenati M, Bhatt DL, et al. Saphenous vein graft failure: from pathophysiology to prevention and treatment strategies. Circulation. 2021;144(9):728-745.
3. Gaudino M, Antoniades C, Benedetto U, et al; ATLANTIC (Arterial Grafting International Consortium) Alliance. Mechanisms, consequences, and prevention of coronary graft failure. Circulation. 2017;136(18):1749-1764.
4. Angiolillo DJ, Galli M, Collet JP, Kastrati A, O’Donoghue ML. Antiplatelet therapy after percutaneous coronary intervention. EuroIntervention. 2022;17(17):e1371-e1396.
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