Aspirin plus ticagrelor/clopidogrel prevents saphenous vein graft failure after CABG surgery

The addition of ticagrelor or clopidogrel to aspirin is effective in preventing saphenous vein graft failure following coronary artery bypass graft (CABG) surgery, results of a systematic review and meta-analysis have shown.

“Dual antiplatelet therapy after surgery should be tailored to the patient by balancing the safety and efficacy profile of the drug intervention against important patient outcomes,” the researchers said.

The databases of Medline, Embase, Web of Science, Cinahl and the Cochrane Library were searched from inception to 25 January 2019 for randomized controlled trials (RCTs) involving participants who received oral antithrombotic drugs (antiplatelets or anticoagulants) to prevent saphenous vein graft failure after CABG surgery.

The primary efficacy and safety endpoints were saphenous vein graft failure and major bleeding, respectively. Secondary endpoints included myocardial infarction and death.

A total of 3,266 citations were identified, with 21 articles relating to 20 RCTs included in the network meta-analysis. The 20 trials comprised 4,803 participants and examined nine different interventions (eight active and one placebo).

There was moderate-certainty evidence supporting the use of dual antiplatelet therapy with either aspirin plus ticagrelor (odds ratio [OR], 0.50, 95 percent confidence interval [CI], 0.31–0.79; number needed to treat=10) or aspirin plus clopidogrel (OR, 0.60, 95 percent CI, 0.42–0.86; number needed to treat=19) in reducing saphenous vein graft failure as compared with aspirin alone. [BMJ 2019;367:l5476]

No strong evidence was found on the differences among antithrombotic therapies as regards major bleeding, myocardial infarction and death.

The possibility of intransitivity could not be ruled out, but between-trial heterogeneity and incoherence were low. Moreover, effect estimates were not changed in sensitivity analysis that used per graft data.

“[A]mong active interventions and based on moderate certainty evidence, dual antiplatelet therapies with aspirin plus ticagrelor or aspirin plus clopidogrel were the most efficacious treatment regimens to prevent saphenous vein graft failure compared with aspirin monotherapy,” the researchers said.

“However, the tradeoff was an increased risk of major bleeding, although the risk did not differ among the drug interventions,” they added.

The 2016 American guidelines recommend aspirin 81 mg (75–100 mg) plus clopidogrel (started early after surgery) for 12 months after CABG in patients with stable coronary artery disease to improve saphenous vein graft patency (class IIb, level of evidence B). On the other hand, the 2017 European guidelines assert that not enough evidence currently exists to generally recommend dual antiplatelet therapy to reduce saphenous vein graft. [Circulation 2016;134:e123-155; Eur Heart J 2018;39:213-260]

The 2015 American Heart Association recommends aspirin plus clopidogrel after off-pump CABG surgery (class I, level of evidence A) to ease the relative hypercoagulable state that patients experience. However, the European guidelines maintain that evidence supporting dual antiplatelet therapy in these patients is weak, while the American guidelines have no comment on this. [Circulation 2016;134:e123-155; Eur Heart J 2018;39:213-260; Circulation 2015;131:927-964]

“Future guideline updates are needed to optimize antithrombotic management of patients undergoing coronary artery bypass graft surgery,” the researchers said. “Meanwhile, dual antiplatelet therapy with aspirin plus ticagrelor or aspirin plus clopidogrel could be considered for most patients after surgery.”