Benefits of 12-Month DAPT After CABG Persist to 5 Years: DACAB

Compared with ticagrelor or aspirin alone, 12 months of dual antiplatelet therapy (DAPT) after coronary artery bypass graft surgery is associated with a reduced risk of MACE that persists out to 5 years without an increase in major bleeding, according to new follow-up from the DACAB trial.

Antiplatelet therapy after CABG has always been considered imperative to prevent graft thrombosis, but the question of whether aspirin is enough has lingered. One-year results of the Chinese DACAB trial were the first to suggest DAPT, compared with monotherapy, holds a benefit in terms of saphenous vein graft patency without a rise in bleeding.

New 5-year data published online this week in the BMJ confirm that protection from early occlusion leads to a “sustained postoperative clinical benefit,” write Yunpeng Zhu, MD (Ruijin Hospital Shanghai Jiao Tong University School of Medicine, China), and colleagues. “We hypothesize that this benefit is due to the protective effect of patent surgical grafts against coronary artery disease progression and acute coronary events.”

Deepak Bhatt, MD (Icahn School of Medicine at Mount Sinai, New York), told TCTMD he is “very supportive” of this concept. However, he noted, “the longer durations of antiplatelet therapy are going to be associated with more bleeding. So the real question then is: what's the optimal duration of dual antiplatelet therapy? We need more data on this topic of patients with CABG and what the optimal cocktail is.”

This query is likely to have a “definitive answer” once data from the ongoing ODIN trial are available, said Bhatt, who serves on the executive committee of the study. The placebo-controlled trial plans to randomize 700 elective CABG patients to only 1 month of DAPT with ticagrelor or aspirin alone.

5-Year Findings

For the analysis, Zhu and colleagues included 477 of the original 500 patients examined in DACAB (81.8% men; mean age 63.1 years). Over a median follow-up period of 61.1 months, more than half (56.0%) were followed up remotely.

At 5 years, MACE had occurred in 22.6%, 32.9%, and 29.9% of the DAPT, ticagrelor monotherapy, and aspirin monotherapy groups, respectively. This translated into a significantly lower 5-year risk of MACE with DAPT compared with aspirin monotherapy (HR 0.65; 95% CI 0.43-0.99). The comparison with ticagrelor monotherapy did not quite reach statistical significance (HR 0.66; 0.44-1.00).

These results were maintained in a sensitivity analysis including only patients who were event free at 1 year as well as in a per-protocol analysis.

Both all-cause and cardiovascular mortality rates at 5 years were numerically higher for patients in the DAPT group compared with both monotherapy arms. Major bleeding was reported in a total of 19 patients: 4.9% on DAPT, 2.5% on ticagrelor monotherapy, and 4.3% on aspirin monotherapy. There was no difference in the risk of major bleeding for DAPT compared with aspirin monotherapy (HR 1.14; 95% CI 0.42-3.14) or ticagrelor monotherapy (HR 1.99; 95% CI 0.60-6.61).

Altogether, the risk of net adverse clinical events at 5 years tended to favor DAPT over aspirin monotherapy (24.4% vs 31.7%; HR 0.67; 95% CI 0.45-1.00), but there was no difference compared with ticagrelor monotherapy (24.4% vs 33.5%; HR 0.70; 95% CI 0.47-1.05).

“Given the substantial rate of cardiovascular events after coronary artery bypass grafting despite standard aspirin therapy, evidence for the clinical effect of ticagrelor dual antiplatelet therapy is of critical importance to inform clinical practice,” Zhu and colleagues write, noting their study was strengthened by an evaluation of three different antiplatelet strategies, good adherence, and a high follow-up rate.

The authors acknowledged that the study was limited by only randomizing treatments for the first year, but pointed out that this is typically the only period when thrombosis occurs. Additionally, the high rate of remote follow-up due to the COVID-19 pandemic “may have affected in particular the ascertainment of silent myocardial infarctions,” Zhu and colleagues write, also noting that their analysis could be underpowered and not necessarily be generalizable to regions that use internal mammary artery grafts more often.

Balancing the Risk-to-Benefit Ratio

In an accompanying editorial, Sigrid Sandner (Medical University of Vienna, Austria), a principal investigator of ODIN, writes that DACAB “is the first study to show a clinical benefit from adding ticagrelor to aspirin in the first year after coronary artery bypass grafting.” She agrees with the authors that this benefit “seems likely to be due to protection of the graft against thrombosis in the early high risk period after surgery. Improved graft patency leads to sustained clinical benefits, which are apparent even when dual antiplatelet therapy is discontinued.”

However, Sandner says a “careful evaluation of the risk-to-benefit ratio of dual antiplatelet therapy” needs to come into play when deciding how long to treat patients, especially with the potential for increased bleeding with DAPT compared with monotherapy recently observed in a meta-analysis.

Today, Bhatt said there is “a lot of variability” as to what antiplatelet regimen is used after CABG, even for patients with ACS. “It really varies a lot from center to center and surgeon to surgeon,” he said. “So that's why I think it shows there's clinical equipoise. Do we need to do a large and definitive randomized clinical trial to nail down what to do?”

For now, his preferred protocol is 1 year of DAPT for patients with ACS, “until any further data show shorter is better.” For elective CABG, Bhatt said, “I would defer to the surgeons certainly for the early period, because in most hospitals they're the ones that are discharging these patients. But it really depends on . . . the details of the surgery and what the surgeon thinks.” For example, he explained, longer DAPT would be better in those where there are “grafts that are going to small-diameter distal vessels or where the runoff isn't great, sort of diffuse disease distally, and one might be worried a bit about graft patency.”

Ultimately, according to Bhatt, the DACAB results add “more data that certainly is supportive of that concept that dual antiplatelet therapy in the right patients provides added clinical benefits.”