Adding ticagrelor to aspirin reduces vein graft failure, increases bleeding after CABG
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Compared with aspirin alone, aspirin plus ticagrelor was associated with reduced risk for vein graft failure and increased risk for clinically important bleeding in patients who underwent CABG, according to a meta-analysis.
For the meta-analysis, researchers included four randomized controlled trials covering 1,316 patients and 1,668 saphenous vein grafts. The primary analysis, which assessed saphenous vein graft failure per graft, included 871 patients (aspirin plus ticagrelor [Brilinta, AstraZeneca] group: median age, 67 years; 15% women; aspirin alone group: median age, 66 years; 15% women).
“Patent grafts are essentially the goal of bypass surgery, and vein grafts are still the most commonly used grafts; while we know that aspirin reduces vein graft failure, what we did not know was whether adding ticagrelor to aspirin would lead to an even greater reduction in vein graft failure, as randomized controlled trials have yielded conflicting results; in addition, what we did not know was whether this would lead to an increased risk of bleeding events,” Mario Gaudino, MD, PhD, Stephen and Suzanne Weiss Professor in Cardiothoracic Surgery in the department of cardiothoracic surgery at NewYork Presbyterian|Weill Cornell Medicine, assistant dean for clinical trials at Weill Cornell Medicine and professor of clinical epidemiology and health services research at Weill Cornell Graduate School, told Healio.
Vein graft failure
The aspirin plus ticagrelor group had a lower rate of saphenous vein graft failure per graft at 1 year compared with the aspirin alone group (11.2% vs. 20%; difference, –8.7 percentage points; 95% CI, –13.5 to –3.1; OR = 0.51; 95% CI, 0.35-0.74; P < .001), Sigrid Sandner, MD, associate professor of cardiac surgery and program director of coronary surgery at Medical University of Vienna, Björn Redfors, MD, PhD, associate professor at Sahlgrenska Academy, University of Gothenburg, Sweden, and consultant cardiologist at Sahlgrenska University Hospital, Gaudino and colleagues wrote.
The rate of saphenous vein graft failure per patient at 1 year was also lower in the aspirin plus ticagrelor group compared with the aspirin alone group (13.2% vs. 23%; difference, –9.7 percentage points; 95% CI, –14.9 to –4.4; OR = 0.51; 95% CI, 0.35-0.74; P < .001), according to the researchers.
However, the aspirin plus ticagrelor group had higher rates than the aspirin-alone group of Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding at 1 year (22% vs. 8.7%; difference, 13.3 percentage points; 95% CI, 8.6-18; OR = 2.98; 95% CI, 1.99-4.47; P < .001).
The rate of BARC type 3 or 5 bleeding was 1.8% in both groups (difference, 0 percentage points; 95% CI, –1.8 to 1.8; OR = 1; 95% CI, 0.37-2.69; P = .99), the researchers wrote.
Net clinical adverse events, a composite of saphenous vein graft failure, clinically relevant bleeding, death, MI and stroke, did not differ between the groups (OR = 1.21; 95% CI, 0.9-1.61).
“[The results were] both expected, because on the one hand, ticagrelor is a very potent platelet inhibitor, [but also] surprising in the magnitude of the association for both vein graft failure and bleeding, and this only becomes clear when the data are pooled,” Gaudino told Healio.
When the researchers compared ticagrelor monotherapy with aspirin monotherapy, they found no differences in saphenous vein graft failure per graft (ticagrelor, 19.3%; aspirin, 21.7%; difference, –2.6 percentage points; 95% CI, –9.1 to 3.9; OR = 0.86; 95% CI, 0.58-1.27; P = .44) or BARC type 2, 3 or 5 bleeding (ticagrelor, 8.9%; aspirin, 7.3%; difference, 1.7 percentage points; 95% CI, –2.8 to 6.1; OR = 1.25; 95% CI, 0.69-2.29; P = .46).
“Overall, the benefit comes at the price of an increase in clinically important bleeding, so assessing individual patient’s risk of bleeding is important,” Gaudino told Healio. “It’s still unclear what the optimal duration of [dual antiplatelet therapy] is, and whether a shorter duration would preserve the benefit on vein graft failure without increasing bleeding risk.”
Consider indication, pathophysiology
In a related editorial, Sunil V. Rao, MD, FSCAI, FACC, director of interventional cardiology at the NYU Langone Health System and president of the Society for Cardiovascular Angiography and Interventions, and E. Magnus Ohman, MD, professor of medicine and vice chair of development and innovation at Duke University School of Medicine and member in the Duke Clinical Research Institute, wrote: “It is instructive to consider both the indication for CABG surgery and the pathophysiology of saphenous vein graft failure. If the patient is undergoing CABG surgery as part of the management strategy for ACS, at least 12 months of treatment with DAPT is indicated after surgery, and ticagrelor is recommended over clopidogrel if the patient is not at high risk of bleeding. The goal of DAPT after an ACS event is to treat the underlying milieu of atherothrombosis and prevent future plaque-rupture events like myocardial infarction regardless of revascularization strategy.
“In the setting of CABG surgery for non-ACS indications (eg, stable angina), the use of DAPT may be of limited value and may be better guided by considering the mechanisms of [saphenous vein graft] occlusion,” they wrote.
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For more information:
Mario Gaudino, MD, PhD, can be reached at mfg9004@med.cornell.edu.
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