Should Dual Antiplatelet Therapy Be Given After Saphenous Vein Bypass Grafting?

The DACAB trial, reported as a late-breaking presentation at the American Heart Association Scientific Sessions in November, found that dual antiplatelet therapy (DAPT) with aspirin and ticagrelor resulted in superior saphenous vein graft (SVG) patency at one year following coronary artery bypass grafting (CABG) compared with low-dose aspirin monotherapy. Rates of major bleeding were similar with the two regimens.

The findings attracted attention, since evidence for the clinical or angiographic benefit of DAPT after CABG with SVGs is scarce. Were the results of DACAB compelling enough to change clinical practice?

“It’s unlikely,” says Cleveland Clinic cardiothoracic surgeon Faisal Bakaeen, MD, who was not involved in the study.

DACAB findings

Chinese researchers randomized 500 patients undergoing elective CABG with SVGs to 90 mg ticagrelor twice daily plus 100 mg aspirin daily, 90 mg ticagrelor twice daily or 100 mg aspirin daily. The primary end point was graft patency, as assessed by CT coronary angiography, at one year. Secondary outcomes included rates of major adverse cardiac events (MACE) and major bleeding.

On intention-to-treat analysis, SVG patency at one year was 88.7 percent in the DAPT arm, 82.8 percent in the ticagrelor monotherapy arm and 76.2 percent in the aspirin monotherapy arm (P = .0006 for DAPT vs. aspirin monotherapy). Rates of MACE were low overall, but were lower with DAPT (1.8 percent) than with aspirin monotherapy (5.4 percent). Rates of major bleeding ranged from 0 percent with aspirin monotherapy to 1.8 percent with DAPT.

Dr. Bakaeen did not find these results convincing. “The study was small and not designed to address the clinical question of outcomes at one year,” he says. “Additionally, outcomes in the control groups were worse than expected. This calls into question the relevance and validity of the findings.”

SVG patency: Why bother?

A major question is why researchers would bother investigating a graft that has fallen out of favor. Yet it appears the issue is not irrelevant.

“Guidelines recommend using more arterial grafts, but SVGs remain the most commonly used grafts in CABG,” Dr. Bakaeen observes. “This is despite significant failure rates for SVGs, in the range of 10 to 25 percent at one year and up to 50 percent at 10 years. Yet in the U.S., approximately 5 percent of patients receive an arterial graft in addition to an internal mammary artery graft to the left anterior descending artery.”

Evidence supporting DAPT

DACAB sought to address a subject for which there is no high-level evidence of DAPT benefits on either graft patency or clinical outcomes. The impact of DAPT on SVG patency up to 12 months after CABG has been evaluated in a limited number of studies, with inconsistent results. This prompted the authors of a 2016 American College of Cardiology (ACC)/American Heart Association (AHA) guideline update to give a “soft” class IIb recommendation for one year of DAPT post-CABG to improve SVG patency, Dr. Bakaeen and a colleague explained in a recent Journal of the American College of Cardiology editorial.

However, three-fourths of patients in DACAB underwent off-pump CABG. While there is no definitive evidence to support DAPT in off-pump CABG patients, notes Dr. Bakaeen, many opinion leaders believe that DAPT may improve patency — and perhaps outcomes — in this patient cohort.

“In CABG, there is a potential hypercoaguable state that is mitigated postoperatively in patients who undergo the procedure with cardiopulmonary bypass,” he explains. “That’s why we feel off-pump CABG patients might benefit from more aggressive antiplatelet therapy. The general preference among many surgeons is to have a low threshold for DAPT for at least a few weeks after off-pump CABG.”

Additionally, post hoc analyses of randomized trials of DAPT suggest that patients with acute coronary syndrome (ACS) undergoing CABG also may benefit from more aggressive antiplatelet therapy. The evidence is compelling enough that the 2016 ACC/AHA guideline update mentioned above gives a class I recommendation for at least 12 months of DAPT post-CABG for ACS patients.

Cleveland Clinic practice

“At Cleveland Clinic, we have a lower threshold for DAPT in patients with ACS, those undergoing off-pump CABG, patients with fresh drug-eluting stents and those with poor targets — i.e., small vessels with diffuse disease,” says Dr. Bakaeen. “These indications are not supported by high-level evidence but are based on our expert opinion, interpretation of literature and individual risk-benefit ratio.”

Cleveland Clinic surgeons maximize the use of arterial grafting and use SVGs less frequently than surgeons at other centers, which makes the issue of DAPT versus monotherapy less of a concern. “We advocate arterial grafts because we want to ensure durability,” Dr. Bakaeen notes. “We believe there is enough evidence that the use of more than one arterial graft is associated with extended survival in appropriately selected patients.”

After CABG, he adds, aspirin is started immediately in all patients and continued for life. DAPT is used selectively. Patients on DAPT for other indications prior to surgery are continued on the regimen after CABG.