DAPT Cuts Saphenous Vein Graft Failure After CABG: Meta-analysis

The use of dual antiplatelet therapy (DAPT), either with clopidogrel or ticagrelor (Brilinta; AstraZeneca), appears to reduce the risk of failing saphenous vein grafts among patients who undergo CABG surgery, a new network meta-analysis suggests.

In 20 randomized controlled trials involving more than 4,800 patients, dual antiplatelet therapy with aspirin and ticagrelor cut the risk of saphenous vein graft failure in half when compared with aspirin therapy alone. Dual use of aspirin and clopidogrel also resulted in a similarly significant reduction in the risk of graft failure compared with aspirin.   

“As interventional cardiologists, we are responsible for sending a lot of people for coronary artery bypass graft surgery,” said senior investigator Rodrigo Bagur, MD (University Hospital/London Health Sciences Center, Western University, Canada). “We all know the benefits of having a left internal mammary artery [LIMA] to the LAD. In the long term, say 10 years, LIMA to the LAD is associated with more than 95% patency, but we know that at 10 years, 50% to 60% of saphenous vein grafts go down. Even as early as 1 year, more than one-quarter of vein grafts have failed. The question is, what can we do to improve vein graft patency?”

In the systematic review and network meta-analysis, which was published October 10, 2019, in the BMJ, the researchers did not observe a significantly increased risk of major bleeding with DAPT, although there was a doubling of the risk of bleeding with ticagrelor compared with clopidogrel when used in combination with aspirin and compared with aspirin alone.

Guideline Authors Should Consider DAPT Post-CABG

Aspirin monotherapy is currently the preferred antiplatelet to prevent saphenous vein graft failure after CABG surgery (class I recommendation, level of evidence A), but there is some uncertainty about adding a P2Y12 inhibitor or oral anticoagulation to aspirin in patients undergoing CABG surgery for stable ischemic heart disease, said Bagur. The network meta-analysis, which allows for the assessment of multiple treatments despite the lack of a direct comparison between drugs, attempted to determine if any of the oral antithrombotic agents could reduce the risk of graft failure following surgery.

The question is, what can we do to improve vein graft patency? Rodrigo Bagur

The review compared eight antithrombotic interventions studied in randomized controlled trials of CABG patients. The study sample included trials ranging in size from 20 to 1,448 patients (ages 44 to 83 years). Most patients were male and 83% underwent elective CABG surgery for stable coronary artery disease. The number of saphenous vein grafts ranged from 1.14 to 3.60 per patient, and drug interventions were started anywhere from 7 days prior to 14 days after surgery. Follow-up in the trials also ranged from 1 month to 8 years.

Compared with aspirin alone, aspirin and ticagrelor use was associated with a halving of the risk of saphenous vein graft vein failure (OR 0.50; 95% CI 0.31-0.79). Similarly, aspirin and clopidogrel use was associated with a 40% lower risk of graft failure compared with aspirin alone (OR 0.60; 95% CI 0.42-0.86). No other antithrombotic agent—whether it was ticagrelor monotherapy, rivaroxaban (Xarelto; Bayer/Janssen) monotherapy, aspirin plus rivaroxaban, or oral anticoagulation with a vitamin K antagonist—was associated with a lower risk of vein graft failure compared with aspirin alone. Use of DAPT, or any antithrombotic agent, was not associated with a reduction in MI or all-cause mortality.

The quality of evidence supporting the reduction in saphenous vein graft failure with DAPT is “moderate,” said Bagur.

Nonetheless, the network meta-analysis includes only randomized trials, which is one of its strengths. As a result, Bagur said he believes the clinical guidelines should be updated to reflect the potential benefit of clopidogrel or ticagrelor added to aspirin for reducing saphenous vein graft failure. While the choice to add an antiplatelet to aspirin should be tailored to the individual, in the classic 60- to 65-year-old CABG patient without high-risk bleeding features, “I would think most patients would be candidates for dual antiplatelet therapy for at least 1 year after surgery,” said Bagur.

Step in the Right Direction

Robert Yanagawa, MD (University of Toronto/St. Michael’s Hospital, Canada), a cardiac surgeon who wasn’t involved in the analysis, agreed that the new report will likely influence the next round of clinical practice guidelines for the medical management of patients following CABG surgery.

“In our institution and others, our patients that undergo CABG for ACS are already treated with DAPT for 1 year according to current practice guidelines,” he told TCTMD via email. “This study is suggesting extending the indication of DAPT for all patients post-CABG once bleeding is considered a nonissue. A major unintended consequence that we as surgeons are very concerned about is pericardial effusion and tamponade. It is reassuring that in this study, there was no difference in the safety endpoint of bleeding.”

The risk estimates for bleeding with the multiple therapies were not statistically significant, but there was an approximate twofold higher risk of major bleeding with aspirin and ticagrelor compared with aspirin alone (OR 1.93; 95% CI 0.30-12.4). There was no signal of bleeding with the clopidogrel and aspirin combination (OR 0.85; 95% CI 0.30-2.37).  

Yanagawa praised the researchers for the “carefully designed and conducted” review and meta-analysis, noting that the group was comprised of cardiac surgeons, cardiologists, and “world-class” statisticians. The new paper, he said, provides important insights to surgeons and cardiologists on the optimal medical management to limit saphenous vein graft failure.

“Those of us that perform surgical revascularization know that graft failure is complex and dependent on conduit quality, target-vessel anatomy, quality of anastomosis, as well as patient-related factors such as renal function and whether surgery is for stable angina versus acute coronary syndrome,” Yanagawa explained. “Having said this, the fact that this study used only randomized controlled trials with strict inclusion criteria, the low heterogeneity in the principle findings and the fact that similar results were shown with two different P2Y12 receptor antagonists suggests that this signal is real.”

Subodh Verma, MD (University of Toronto/St. Michael’s Hospital, Canada), another cardiac surgeon, agreed. The new study, which he called a definitive and high-quality analysis, “provides cardiac surgeons with cogent evidence of DAPT for graft patency.” 

Despite the high praise for the study, Yanagawa said some important questions remain for the field. Such questions include: What is the optimal duration for DAPT? Is there an advantage of one P2Y12 receptor antagonist over another? Does it matter if the CABG is performed on- or off-pump? Should patients that require oral anticoagulation for post-operative atrial fibrillation be on triple therapy? Do patients with revascularization with multiple arterial grafts also gain a similar benefit with DAPT?

“This report leads to more questions than answers, but it is an important step in the right direction,” said Yanagawa.