Potent DAPT After CABG Halves Vein Graft Failure

Doubling up on antiplatelet agents after coronary artery bypass graft (CABG) surgery cut down on graft failure but increased bleeding risk at least as much, pooled clinical trial data showed.

Saphenous vein graft failure risk at a median of 1 year post-surgery was nearly halved with the combination of ticagrelor (Brilinta) and aspirin compared with aspirin alone (11.2% vs 20% per graft and 13.2% vs 23.0% per patient, both OR 0.51, 95% CI 0.35-0.74), Mario Gaudino, MD, PhD, of NewYork-Presbyterian Hospital in New York City, and colleagues reported in JAMA.

Clinically important bleeding (BARC type 2, 3, or 5 events) was threefold more likely among patients who received dual antiplatelet therapy (DAPT) with ticagrelor across the four trials in the meta-analysis (22.1% vs 8.7%, P<0.001), which was driven by the less serious bleeds. Events that led to transfusion, surgery, or death (BARC type 3 or 5 bleeding) occurred in 1.8% of both groups.

All-cause mortality risk came out more than double with ticagrelor DAPT but, with only 13 deaths overall in the trials, the difference was not statistically significant (2.1% vs 0.9%, HR 2.26, 95% CI 0.70-7.35).

Combining all those outcomes along with myocardial infarction and stroke together, net adverse clinical events didn't show an overall significant advantage to ticagrelor DAPT (OR 1.21, 95% CI 0.90-1.61).

The researchers called their patient-level data synthesis of all four randomized clinical trials with angiographic follow-up "solid evidence," whereas the individual trials were universally underpowered to find even a moderate difference in bleeding event risk.

"Taken together, the present analysis suggests that a patient's individual risk of graft failure, ischemic events, and bleeding needs to be weighed carefully when deciding whether to add ticagrelor to aspirin after CABG surgery," Gaudino and colleagues concluded. "Longer-term follow-up is required to fully evaluate a potential benefit of ticagrelor DAPT on clinical events."

An accompanying editorial by Sunil V. Rao, MD, and E. Magnus Ohman, MD, both of the Duke Clinical Research Institute in Durham, North Carolina, argued for limiting that decision for now to only those patients having CABG after acute coronary syndrome (ACS).

U.S. guidelines, they noted, recommend at least a year of DAPT (ticagrelor for those not at high bleeding risk) after surgery for that population as part of the management strategy for ACS to "treat the underlying milieu of atherothrombosis and prevent future plaque-rupture events like myocardial infarction regardless of revascularization strategy."

But for stable angina and other non-ACS indications, the editorialists pointed to the mechanism of saphenous graft failure as largely being thrombosis early after surgery, then intimal hyperplasia over the next months, and atherosclerosis starting within the first year.

Thus, DAPT, if it is considered "may be most beneficial early after CABG surgery, with a transition to aspirin alone after a certain period to reduce the risk of bleeding," Rao and Ohman wrote. "Such strategies have not yet been tested and require evaluation in adequately powered randomized trials."

Study Details

The meta-analysis included four randomized clinical trials -- TAP-CABG, DACAB, TARGET, and POPular CABG -- with a total of 1,316 patients and 1,668 saphenous vein grafts. Three of the trials had data for the primary analysis on graft failure, totalling 871 patients (435 treated with ticagrelor DAPT). Participants' median age was about 67, with about 15% being women. Median duration of randomized treatment was 1 year.

The researchers obtained patient-level data from the trials, which included graft occlusion or percent stenosis data to harmonize the definitions across trials and to centrally adjudicate events. Graft failure was defined by saphenous vein graft occlusion or stenosis greater than 50% per graft on invasive angiography or CT angiography at the trial's protocol-defined follow-up. Bleeding events were also re-adjudicated by BARC criteria.

The results were consistent across patient subgroups.

Ticagrelor monotherapy did not appear to help prevent saphenous vein graft failure (19.3% vs 21.7% incidence at 1 year, OR 0.86, 95% CI 0.58-1.27) nor increase risk of BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, OR 1.25, 95% CI 0.69-2.29).

However, "these findings should be interpreted with caution given the small sample size (two studies and 750 patients) and limited statistical power," the editorialists noted.

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