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

The researchers hypothesize that adding ticagrelor to aspirin for the first year preserves graft patency and reduces later events.

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.”

  • Zhu reports receiving personal fees and non-financial support from AstraZeneca, Johnson & Johnson, Medtronic, Novartis, Sanofi, and Chugai and grants from the Science and Technology Commission of Shanghai Municipality and the Shanghai Shenkang Hospital Development Centre.
  • Sandner reports no relevant conflicts of interest.
  • Bhatt reports serving on advisory boards for AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; serving on boards of directors for AngioWave, the Boston VA Research Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, the Society of Cardiovascular Patient Care, and TobeSoft; holding stock or stock options with AngioWave, Bristol Myers Squibb, and DRS.LINQ; serving as inaugural chair of the American Heart Association Quality Oversight Committee; being a consultant for Broadview Ventures; serving on data monitoring committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), Contego Medical (chair, PERFORMANCE 2 trial), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; and for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT trial); receiving honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News,, and chair of the ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Boehringer), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (cochair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees), and Wiley (steering committee); having other relationships with Clinical Cardiology (deputy editor), NCDRACTION Registry Steering Committee (chair), and VA CART Research and Publications Committee (chair); being named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon (neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); receiving research funding from 89Bio, Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, Myo-Kardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and Youngene; receiving royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has been a site coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; being a trustee for the American College of Cardiology; and has performed unfunded research for FlowCo and Takeda.