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Drug Combo Boosts 1-Year CABG Vein Graft Patency

— Ticagrelor and aspirin together better than aspirin alone

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After elective coronary artery bypass grafting (CABG), dual antiplatelet therapy (DAPT) provided a boost in saphenous vein graft (SVG) patency unlike what was seen with ticagrelor (Brilinta) or aspirin alone, researchers reported.

SVGs stayed open to 1 year 88.7% of the time when patients took ticagrelor and aspirin after surgery, 82.8% when they took ticagrelor alone, and 76.5% with aspirin alone. DAPT wielded a statistically significant advantage over aspirin alone (P<0.001), but ticagrelor alone did not prove to be better than aspirin (P=0.10), according to Qiang Zhao, MD, PhD, of Ruijin Hospital Shanghai Jiao Tong University School of Medicine in China, and colleagues.

Action Points

  • Note that this randomized trial found that ticagrelor (Brilinta) plus aspirin was superior to aspiring alone in maintaining saphenous vein graft (SVG) graft patency after coronary artery bypass grafting.
  • Be aware that SVG patency is not a "hard" clinical outcome -- further research examining pain, function, and mortality is needed.

The 12% absolute difference between DAPT and aspirin alone translated into a number needed to treat of eight to prevent loss of patency of one saphenous vein graft over 1 year, the investigators noted in the .

Their data from the Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery (DACAB) trial were previously reported at the 2017 American Heart Association meeting.

Five major bleeding episodes occurred over 1-year follow-up: three with DAPT and two with ticagrelor alone. There was no difference the rates of major adverse cardiovascular events, atrial fibrillation, or recurrent angina among treatment groups, Zhao's group reported.

"In this trial, ticagrelor + aspirin was superior to aspirin alone in maintaining SVG patency for up to 1 year after elective CABG surgery in a general population that included a subgroup of patients with ACS [acute coronary syndrome] and stable ischemic heart disease," they concluded, adding that these findings confirm and extend what was previously reported in other studies.

What remains to be seen is whether the improvement in graft patency has any effect on clinical outcomes, the authors acknowledged.

"Fundamentally, angiographic vein graft patency is an imaging outcome and not a direct measure of how a patient feels, functions, or survives. For these reasons, it is premature to endorse the routine addition of ticagrelor to aspirin after CABG surgery," emphasized John Alexander, MD, MHS, of Duke Clinical Research Institute in Durham, North Carolina, in an .

"Data from randomized trials evaluating clinical outcomes are needed to understand the effects of ticagrelor on ischemic events and bleeding. Such a trial would be large, on the order of several thousand patients," Alexander said. He cited -- a pivotal trial of ticagrelor in patients undergoing CABG -- as one adequately powered clinical trial that will inform patient outcomes associated with improved vein graft patency.

DACAB was a 500-person randomized trial with groups getting ticagrelor alone (90 mg twice daily; n=166), aspirin alone (100 mg once daily; n=166), or the two drugs together (n=168) within 24 hours following elective CABG. Participating sites were six tertiary hospitals in China that enrolled patients, ages 18-80, in 2014-2015.

There was a total of 1,460 SVGs implanted over the course of the study. Baseline characteristics were well balanced across the three treatment groups.

On subgroup analysis, it was the patients with higher and intermediate SYNTAX scores that had the most benefit with ticagrelor and aspirin combined over aspirin alone (P=0.04 for interaction).

Zhao's group acknowledged that there was no blinding of patients nor treating physicians in this trial, though patency was adjudicated via multislice CT angiography or coronary angiography by a blinded committee. They also suggested that DACAB was underpowered to detect a benefit to ticagrelor alone.

Moreover, these findings cannot be generalized to arterial graft patency, the investigators said. Similarly, excluding patients age >80 was another limitation to the generalizability of the trial's results, according to Alexander.

Nevertheless, DACAB "was a well-conducted study that enrolled a relevant population," he stated. "Most patients had stable or unstable angina without recent MI. This is important because ticagrelor has established benefit, over and above clopidogrel [Plavix], in patients with MI, including the subset who subsequently undergo CABG surgery."

  • author['full_name']

    Nicole Lou is a reporter for ֱ, where she covers cardiology news and other developments in medicine.

Disclosures

The study was funded by AstraZeneca.

Zhao disclosed relevant relationships with Medtronic, Johnson & Johnson, Novartis, Sanofi, and Bayer. Co-authors disclosed multiple relevant relationships with industry.

Alexander disclosed relevant relationships with AstraZeneca, Bristol-Myers Squibb (BMS), Janssen Pharmaceuticals, Merck, Novo Nordisk Pharmaceuticals, Pfizer, Portola Pharmaceuticals, Veterans Affairs Cooperative Studies Program, and Zafgen and support from BMS, Boehringer Ingelheim, CryoLife, CSL Behring, the FDA, the NIH, Tenax Therapeutics, and VoluMetrix.

Primary Source

Journal of the American Medical Association

Zhao Q, 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; DOI:10.1001/jama.2018.3197.

Secondary Source

Journal of the American Medical Association

Alexander JH "Ticagrelor following coronary artery bypass grafting: For better vein graft patency or better patient outcomes?" JAMA 2018; DOI:10.1001/jama.2018.3793.