What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Post-coronary artery bypass grafting (CABG) (n=3133). Intervention: Aspirin monotherapy vs. Placebo. Primary outcome: Graft patency at 3 months and beyond (OR 1.9, 95% CI 1.3-2.8).

September 1, 2018Open Access

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

ACAdam ChakosThe University of Sydney DJDean JbaraCollaborative Research Group KSKamal SinghMinistry of Health and Family Welfare

Key Result

Aspirin monotherapy and dual antiplatelet therapy significantly improved graft patency compared to placebo following CABG, though DAPT did not show a statistically significant benefit over aspirin.

Study Design

Type

Meta-Analysis (n=3,133)

Multicenter

Yes

Structured PICO

Does single or dual antiplatelet therapy improve graft patency in patients following coronary artery bypass grafting compared to placebo or aspirin monotherapy?

Population

16 RCTs pooling 3,133 patients following coronary artery bypass grafting (CABG) with an average of 2.43 grafts per patient (predominantly saphenous vein grafts).

Intervention

Antiplatelet therapy including aspirin monotherapy, aspirin + dipyridamole, aspirin + clopidogrel, or aspirin + ticagrelor.

Comparator

Placebo or aspirin monotherapy.

Outcome

Graft patency at three months and beyond (assessed by angiographic follow-up at a mean of 10.4 months).surrogate

Aspirin monotherapy and dual antiplatelet therapy significantly improve post-CABG graft patency compared to placebo, with DAPT showing a non-significant trend for further benefit over aspirin alone.

Main Result

Effect estimate: OR 1.9 (95% CI 1.3-2.8)

Limitations

Paucity of RCT evidence for contemporary DAPT (aspirin + clopidogrel or ticagrelor)
Potential under-powering and increased heterogeneity due to variability between patency results
Heterogeneity in drug dosage and operative technique
Exclusion of non-contemporary agents or those with only a single contributing study
Variations in operative improvements and patient selection over the long publication timeframe (1981-2016)

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.

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