Network meta-analysis of antiplatelet therapy following coronary artery bypass grafting (CABG): none versus one versus two antiplatelet agents

Abstract

Background: Numerous agents have been trialed following coronary artery bypass grafting (CABG) to maintain long-term graft patency. While clear evidence exists for the use of aspirin in maintaining graft patency, the role of dual-antiplatelet therapy in CABG patients is not as well established. This network meta-analysis aimed to compare the short-term post-CABG graft patency outcomes for patients with none, one or two antiplatelet agents.

Methods: Electronic databases were queried for randomized controlled trials comparing CABG graft patency rates at three months and beyond using various antiplatelet agents or placebo. Drug and graft patency data were compared using a mixed treatment comparison under a Bayesian hierarchical framework. A random-effects consistency model was applied. Direct and indirect comparisons were made between drugs and used to determine the relative efficacy for graft patency.

Results: The literature search identified 16 papers fulfilling the inclusion criteria, including a total of 3,133 patients with an average of 2.43 [95% confidence interval (CI): 2.20-2.66] grafts per patient. Graft types were incompletely reported, however, saphenous vein grafts (SVGs) were predominantly used [where specifically reported: 4,490 SVG, 1,226 internal mammary artery (IMA) grafts]. In all, five different agents and placebo in various regimens were compared by results of angiographic follow-up conducted at a mean of 10.4 months (95% CI: 9.28-11.5 months). Compared to placebo, aspirin alone [odds ratio (OR) 1.9; 95% credible interval (CrI): 1.3-2.8], aspirin + dipyridamole (OR 1.9; 95% CrI: 1.3-2.6), aspirin + clopidogrel (OR 2.9; 95% CrI: 1.5-5.7) and aspirin + ticagrelor (OR 3.8; 95% CrI: 1.2-13.0) significantly improved graft patency. When compared to aspirin monotherapy, aspirin + clopidogrel (OR 1.6; 95% CrI: 0.86-2.7) and aspirin + ticagrelor (OR 2.0; 95% CrI: 0.69-6.3) had OR that suggested a trend favoring patency compared to aspirin monotherapy, however, these results did not reach significance. Sub-group analysis of SVG graft patency was unable to reach significance (only eight studies with six treatment comparisons were evaluated). Secondary endpoints of death, bleeding, myocardial infarction and cerebrovascular accident were incompletely reported and were pooled but not compared between drug treatment arms.

Conclusions: Aspirin monotherapy and dual antiplatelet therapy (DAPT) provided significant all-graft patency benefit compared to placebo at three months and beyond. A trend existed for DAPT to improve graft patency compared to aspirin, although this did not reach statistical significance. Further randomized controlled studies comparing aspirin monotherapy to DAPT are required to determine the utility of DAPT in CABG patients for maintaining graft patency.

Keywords: Antiplatelet; coronary artery bypass graft; dual antiplatelet therapy (DAPT); graft patency; network meta-analysis.

Figure 1

Network diagram of treatments and direct comparisons available from included studies. The thickness of the links between treatments reflects the number of studies in that link (annotated for all links with more than one study).

Figure 2

Network meta-analysis results for patency at follow-up with placebo and aspirin (ASA) used as reference (none versus one versus two antiplatelet agent comparison).

Figure 3

Rank probability for graft patency at follow-up. The probability of each treatment ranking as most effective (1^st) to least effective (6^th) is shown. For example, aspirin + ticagrelor has 65% probability of ranking as the most effective treatment (1^st) and an approximately 1% probability as ranking as the least effective (6^th best) treatment.

Figure S1

PRIMSA flow chart detailing the literature search process for randomized controlled trials comparing graft patency between placebo or drug arms. RCT, randomized controlled trial.

Figure S2

Direct, indirect and pooled network comparisons between treatments using a random effects model. Heterogeneity is shown for comparisons with at least 2 sets of direct evidence. ASA, aspirin; CrI, credible interval.

Figure S3

Sub-group analysis of saphenous vein graft (SVG) patency between different agents from 8 of 16 included studies. Placebo and aspirin used as reference.