Ticagrelor for patients undergoing coronary artery bypass grafting: A meta-analysis of randomized controlled trials

Abstract

Objective

Ticagrelor may be an alternative to aspirin as it provides robust and consistent platelet inhibition. However, the effect of ticagrelor treatment in patients undergoing coronary artery bypass grafting (CABG) has not been well confirmed. We conducted a meta-analysis to appraise whether ticagrelor therapy affects outcomes in CABG patients.

Methods

We searched PubMed, Embase, EBSCO, and Cochrane databases from its inception up to 4 December 2020 for randomized controlled trials that assessed ticagrelor versus non-ticagrelor in patients undergoing CABG. The primary outcome was the incidence of saphenous vein graft (SVG) occlusion at 1 year after CABG. Secondary outcomes were SVG occlusion at 7 days, major adverse cardiovascular events (MACE), and bleeding requiring reoperation.

Results

Seven trials including 4305 patients (2153 randomized to ticagrelor therapy and 2152 to non-ticagrelor therapy) were included. One-hundred and thirty of 1140 patients (11.4%) randomized to the ticagrelor group versus 175 of 1220 patients (14.3%) randomized to the non-ticagrelor group experienced SVG occlusion at 1 year after CABG. Compared to the control group, ticagrelor therapy yielded a significantly lower risk of SVG occlusion [RR 0.79 (0.64–0.97), p = 0.03]. In the subgroup analysis, ticagrelor plus aspirin compared with aspirin alone did not decrease the risk of SVG occlusion after 1 year [RR 0.65 (0.40–1.07), p = 0.09]. There was no difference in the incidence of SVG occlusion at 7 days [RR 0.67 (0.42–1.06), p = 0.09], MACE up to 1 year [RR 0.99 (0.81–1.21), p = 0.90], or bleeding requiring reoperation [RR 1.16 (0.80–1.70), p = 0.44].

Conclusions

Compared with non-ticagrelor therapy, ticagrelor decreased the risk of saphenous vein graft occlusion after 1 year in patients undergoing elective CABG with saphenous vein grafting.

Keywords

Ticagrelor coronary artery bypass grafting saphenous vein graft occlusion randomized controlled trial meta-analysis

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References

Alexander

Smith

. Coronary-artery bypass grafting. New Engl J Med 2016; 374: 1954–1964.

Aldea

Bakaeen

Pal

, et al. The society of thoracic surgeons clinical practice guidelines on arterial conduits for coronary artery bypass grafting. Ann Thoracic Surg 2016; 101: 801–809.

Desai

Cohen

Naylor

, et al. A randomized comparison of radial-artery and saphenous-vein coronary bypass grafts. New Engl J Med 2004; 351: 2302–2309.

Halabi

Alexander

Shaw

, et al. Relation of early saphenous vein graft failure to outcomes following coronary artery bypass surgery. Am J Cardiol 2005; 96: 1254–1259.

Gaudino

Antoniades

Benedetto

, et al. Mechanisms, consequences, and prevention of coronary graft failure. Circulation 2017; 136: 1749–1764.

Yanagawa

Ruel

Bonneau

, et al. Dual antiplatelet therapy use by Canadian cardiac surgeons. J Thoracic Cardiovasc Surg 2015; 150: 1548–1554.

Mannacio

Di Tommaso

Antignan

, et al. Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of coronary arteRY bypaSS occlusion after off-pump procedures) randomised study. Heart 2012; 98: 1710–1715.

Gurbel

Bliden

Zaman

, et al. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the clopidogrel loading with eptifibatide to arrest the reactivity of platelets (CLEAR PLATELETS) study. Circulation 2005; 111: 1153–1159.

Schömig

. Ticagrelor--is there need for a new player in the antiplatelet-therapy field? New Engl J Med 2009; 361: 1108–1111.

10.

Parodi

Xanthopoulou

Bellandi

, et al. Ticagrelor crushed tablets administration in STEMI patients: the MOJITO study. J Am Coll Cardiol 2015; 65: 511–512.

11.

Shamseer

Moher

Clarke

, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 349: g7647.

12.

Held

Asenblad

Bassand

, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (platelet inhibition and patient outcomes) trial. J Am Coll Cardiol 2011; 57: 672–684.

13.

Saw

Wong

Mayo

, et al. Ticagrelor and aspirin for the prevention of cardiovascular events after coronary artery bypass graft surgery. Heart 2016; 102: 763–769.

14.

Zhao

Zhu

, et al. Effect of ticagrelor plus aspirin, ticagrelor alone, or aspirin alone on saphenous vein graft patency 1 year after coronary artery bypass grafting: a randomized clinical trial. Jama 2018; 319: 1677–1686.

15.

Schunkert

Boening

von Scheidt

, et al. Randomized trial of ticagrelor versus aspirin in patients after coronary artery bypass grafting: the TiCAB trial. Eur Heart J 2019; 40: 2432–2440.

16.

Feng

Zhou

, et al. Antiplatelet effects of ticagrelor versus clopidogrel after coronary artery bypass graft surgery: a single-center randomized controlled trial. J Thoracic Cardiovasc Surg 2019; 158: 430–437.e4.

17.

Willemsen

Janssen

PWA

Peper

, et al. Effect of adding ticagrelor to tandard aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (POPular CABG): a randomized, double-blind, placebo-controlled trial. Circulation 2020; 142: 1799–1807.

18.

Tang

Fan

Zhang

, et al. Aspirin plus ticagrelor or clopidogrel on graft patency one year after coronary bypass grafting: a single-center, randomized, controlled trial. J Thoracic Dis 2021; 13: 1697–1705.

19.

Husted

Emanuelsson

Heptinstall

, et al. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006; 27: 1038–1047.

20.

Zimmermann

Gams

Hohlfeld

. Aspirin in coronary artery bypass surgery: new aspects of and alternatives for an old antithrombotic agent. Eur J Cardio-Thoracic Surg 2008; 34: 93–108.

21.

Kulik

Ruel

Jneid

, et al. Secondary prevention after coronary artery bypass graft surgery: a scientific statement from the American heart association. Circulation 2015; 131: 927–964.

22.

Valgimigli

Mehran

Franzone

, et al. Ticagrelor monotherapy versus dual-antiplatelet therapy after PCI: an individual patient-level meta-analysis. JACC Cardiovasc Inter 2021; 14(4): 444–456.

23.

Hong

Ahn

Kim

, et al. Effect of ticagrelor monotherapy on mortality after PCI: a systematic review and meta-analysis of randomized trials including 26143 patients. Eur Heart J Cardiovasc Pharmacother 2022; 8: 48–55.

24.

Brilakis

Held

Meier

, et al. Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: insights from the PLATelet inhibition and patient outcomes (PLATO) trial. Am Heart J 2013; 166: 474–480.

25.

Gao

Zheng

, et al. Aspirin plus clopidogrel therapy increases early venous graft patency after coronary artery bypass surgery a single-center, randomized, controlled trial. J Am Coll Cardiol 2010; 56: 1639–1643.