Efficacy and Safety of Dual Antiplatelet Therapy on Graft Patency After Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial

Document Type : Original Article


1 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

2 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.


Background: Early vein graft occlusion after coronary artery bypass grafting (CABG) is one of the major problems after the surgery which directly impacts its short- and long-term outcomes. One of the potential explanations is aspirin resistance. The aim of this study was to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin compared with aspirin alone on the reduction of early graft occ usion.
Methods: In a multicenter randomized controlled trial with a parallel design, from 2012 to 2015 among 1165 patients, we compared 140 candidates for CABG: 71 in the DAPT group (300 mg c of clopidogrel and 80–325 mg of aspirin) and 69 in the aspirin group. The primary outcome was graft patency assessed by coronary computed tomography angiography performed at 6 months’ follow-up. Bleeding complications were considered the secondary outcome.
Results: Saphenous vein grafts were occluded in 10 (14.1%) patients in the DAPT and 11 (15.9%) in the control group (P = 0.758). After adjustments for study centers, the associations remained unchanged (OR [95% CI]: 1.49 [0.59–3.74]). Bleeding endpoints were also similar in the 2 groups (P > 0.05).
Conclusions: Our study did not demonstrate the superiority of the DAPT regimen over aspirin monotherapy in patients undergoing elective CABG. Larger multicenter studies may provide more evidence. 


1. Blessing F, Jaeger BR, Oberhoffer M,
Reichart B, Seidel D. [Prevention of early
graft occlusion after coronary bypass
grafting by post-operative reduction of
plasma fibrinogen by H.E.L.P. apheresis.
First evaluation of 12 patients treated during
our study (44 bypasses)]. Zeitschrift fur
Kardiologie. 2003;92(Suppl 3):III42-7. Epub
2003/12/10. Verhinderung von
Fruhverschlussen nach koronarer
Bypassoperation durch postoperative
Reduktion des Plasmafibrinogens mittels
H.E.L.P.-Apherese. Erste Auswertung von
12 im Rahmen dieser Studie behandelten
Patienten (44 Bypassen).
2. Cambria-Kiely JA, Gandhi PJ. Possible
mechanisms of aspirin resistance. Journal of
thrombosis and thrombolysis.
2002;13(1):49-56. Epub 2002/05/08.
3. Gluckman TJ, McLean RC, Schulman SP,
Kickler TS, Shapiro EP, Conte JV, et al.
Effects of aspirin responsiveness and platelet
reactivity on early vein graft thrombosis
after coronary artery bypass graft surgery.
Journal of the American College of
Cardiology. 2011;57(9):1069-77. Epub
4. Kayacioglu I, Gunay R, Saskin H, Idiz M,
Sensoz Y, Ates M, et al. The role of
clopidogrel and acetylsalicylic acid in the
prevention of early-phase graft occlusion
due to reactive thrombocytosis after
coronary artery bypass operation. The heart
surgery forum. 2008;11(3):E152-7. Epub
5. Ibrahim K, Tjomsland O, Halvorsen D,
Wiseth R, Wahba A, Karevold A, et al.
Effect of clopidogrel on midterm graft
patency following off-pump coronary
revascularization surgery. The heart surgery
forum. 2006;9(6):E581-856. Epub
6. de Vries, M.R., Vein graft failure: from
pathophysiology to clinical outcomes.
Nature Reviews Cardiology, 2016.
7. Saw, J., Comparison of long-term usefulness
of clopidogrel therapy after the first
percutaneous coronary intervention or
coronary artery bypass grafting versus that
after the second or repeat intervention. The
American journal of cardiology, 2004. 94(5):
p. 623-625.
8. Fox, K.A., Benefits and Risks of the
Combination of Clopidogrel and Aspirin in
Patients Undergoing Surgical
Revascularization for Non–ST-Elevation
Acute Coronary Syndrome The Clopidogrel
in Unstable angina to prevent Recurrent
ischemic Events (CURE) Trial. Circulation,
2004. 110(10): p. 1202-1208.
9. Gao G, Zheng Z, Pi Y, Lu B, Lu J, Hu S. et
al. Aspirin plus clopidogrel therapy
increases early venous graft patency after
coronary artery bypass surgery a single-center, randomized, controlled trial. Journal
of the American College of Cardiology.
2010;56(20):1639-43. Epub 2010/11/06.
10. Mannacio, V.A., Aspirin plus clopidogrel for
optimal platelet inhibition following offpump coronary artery bypass surgery: results
from the CRYSSA (prevention of Coronary
arteRY bypaSS occlusion After off-pump
procedures) randomised study. Heart, 2012.
98(23): p. 1710-1715.
11. Gasparovic, H., Impact of dual antiplatelet
therapy on outcomes among aspirin-resistant
patients following coronary artery bypass
grafting. The American journal of
cardiology, 2014. 113(10): p. 1660-1667.
12. Kulik, A., The clopidogrel after surgery for
coronary artery disease (CASCADE)
randomized controlled trial: clopidogrel and
aspirin versus aspirin alone after coronary
bypass surgery [NCT00228423]. Trials,
2005. 6(1): p. 1.
13. Van Diepen S, Fuster V, Verma S, Hamza
TH, Siami FS, Goodman SG, et al. Dual
Antiplatelet Therapy Versus Aspirin
Monotherapy in Diabetics With Multivessel
Disease Undergoing CABG: FREEDOM
Insights. J Am Coll Cardiol. 2017 Jan
14. Verma, S., Should dual antiplatelet therapy
be used in patients following coronary artery
bypass surgery? A meta-analysis of
randomized controlled trials. BMC surgery,
2015. 15(1): p. 1.
15. Une D, Al-Atassi T, Kulik A, Voisine P, Le
May M, et al. Ruel M. Impact of clopidogrel
plus aspirin versus aspirin alone on the
progression of native coronary artery disease
after bypass surgery: analysis from the
Clopidogrel After Surgery for Coronary
Artery DiseasE (CASCADE) randomized
trial. Circulation. 2014 Sep 9;130(11 Suppl