Influence of Baseline HbA1c and Antiplatelet Therapy on 1-Year Vein Graft Outcome

Background The influence of baseline HbA1c levels on vein graft outcomes post coronary artery bypass grafting (CABG) remains unclear. Objective The purpose of this study was to assess the association between baseline HbA1c and 1-year vein graft patency, and the effects of antiplatelet therapy on the 1-year vein graft patency after CABG in patients with baseline HbA1c <6.5% vs ≥6.5%. Methods We examined the subgroups with baseline HbA1c <6.5% vs ≥6.5% from the DACAB trial (NCT02201771), in which 500 patients were randomly allocated to receive ticagrelor plus aspirin (T+A), ticagrelor alone (T), or aspirin alone (A) for 1 year after CABG. The primary outcome was the vein graft patency (FitzGibbon grade A) at 1 year. Results A total of 405 patients with available baseline HbA1c data were included in this subgroup analysis. Of them, there were 233 patients (678 vein grafts) with baseline HbA1c <6.5% and 172 patients (512 vein grafts) with baseline HbA1c ≥6.5%. Compared with the HbA1c <6.5% subgroup, the HbA1c ≥6.5% subgroup showed worse 1-year vein graft patency (adjusted odds ratio [OR] for nonpatency: 1.69, 95% confidence interval [CI]: 1.08-2.64). T+A showed higher vein graft patency than A in both HbA1c <6.5% (adjusted OR for nonpatency: 0.34, 95% CI: 0.15-0.75) and HbA1c ≥6.5% subgroups (adjusted OR for nonpatency: 0.45, 95% CI: 0.19-1.09), without an interaction effect (P for interaction = 0.335), whereas T did not show more significant improvement than A in both subgroups. Conclusions In the DACAB trial, lower baseline HbA1c was associated with higher vein graft patency 1 year after CABG. T+A improved 1-year vein graft patency vs A, irrespective of baseline HbA1c.

D iabetes mellitus (DM) is associated with a worse prognosis of coronary artery diseases (CAD). 1 A large study of 1.9 million people showed that type 2 diabetes was positively associated with the incidence of stable angina and myocardial infarction. 2 Approximately twothirds of the deaths in patients with DM are attributable to CAD, 1 and CAD occurs approximately 15 years earlier in patients with DM than those without. 3 A systematic review indicated that 32.2% of patients with DM have CAD. 4 Approximately 70% of the patients 65 years or older and with DM will die of CAD or stroke. 1 For diabetic patients with 1-or 2-vessel disease, including the proximal left anterior descending artery, 3-vessel disease, or left main coronary artery disease, the current European guidelines made a Class I recommendation on coronary artery bypass grafting (CABG) as the gold standard for myocardial revascularization. 5 The internal mammary artery graft is often considered the first choice because of its higher 10-year patency rate (>90%) and improved survival compared with any other grafts. 6 Other arterial grafts (especially the radial artery) should be preferred as the second choice. 7 Nevertheless, the saphenous vein grafts remain the most commonly used graft worldwide, with occlusion rates of 11% within 1 year after surgery and 40% to 50% at 10 years. 8 Although blood glucose levels are punctual and vary greatly within a given day, glycated hemoglobin (HbA1c) levels represent the glucose levels over the past 90 days and can be used to evaluate glycemic control. 9 The DCCT (Diabetes Control and Complications Trial) showed that high HbA1c levels were a predictor of microvascular complications of DM and that maintaining HbA1c at <7% decreased the occurrence of diabetic retinopathy, nephropathy, and neuropathy, as well as cardiovascular risk and mortality. [10][11][12] Recently, several studies revealed that higher preoperative HbA1c levels were associated with a higher cardiovascular risk and long-term mortality after CABG, irrespective of DM. [13][14][15] However, the effect of HbA1c control on vein graft outcome is still unclear, especially in the early term.
Therefore, this post hoc subgroup analysis of the DACAB (Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery) trial aimed to assess the effects of ticagrelor with or without aspirin vs aspirin alone on the 1-year vein graft patency after CABG according to baseline HbA1c levels. The results could provide additional data for the personalization of antiplatelet therapy after CABG. The present analysis was approved by the ethics committee of the Ruijin Hospital Shanghai Jiao Tong University School of Medicine. All participants or their legal representatives provided written informed consent before study enrollment. This consent included the post hoc analyses of the trial data.

METHODS
PRIMARY OUTCOME/ASSESSMENT. The outcome of the grafts was assessed by computed tomography angiography or coronary angiography and graded as described by FitzGibbon et al. 18   interaction. An HbA1c cutoff point of 6.5% was used in the analyses. Besides, HbA1c cutoff point of 7%, 7.5%, and 8% was used as sensitive analysis.
A 2-sided level of significance of 0.05 was applied.

RESULTS
We also analyzed artery graft outcome between the baseline HbA1c <6.5% vs $6.5% subgroups. In the per-graft analysis, the 1-year artery graft patency (FitzGibbon grade A) and nonocclusion (FitzGibbon grade AþB) rates were 96.9% and 97.4% in the HbA1c <6.5% subgroup and 97.7% and 98.5% in the HbA1c $6.5% subgroup, respectively. There was no difference in artery graft outcomes between the baseline HbA1c <6.5% vs $6.5% subgroups (all P > 0.05) (Supplemental Table 5).  Table 4).  Table 4).  There were no significant differences between the baseline HbA1c <6.5% and $6.5% subgroups and between antiplatelet treatments (all P > 0.05) ( Table 5).  Nevertheless, using DM alone can bias the results because patients with DM with well-controlled glycemia will display a better microvascular and macrovascular status than patients with DM with poorly controlled glycemia. 21 In the same line of thought, patients without DM with poorly controlled glycemia but not overt DM might have poorer outcomes than those with well-controlled glycemia. 15 Hence, using HbA1c, which represents the overall glycemic control over the past 3 months, 9 might yield more precise results and allow for more personalized medicine through better risk assessment. Maintaining low HbA1c levels has been shown to decrease the incidence of diabetic microvascular and macrovascular complications [10][11][12] and cardiovascular death in general. 14 Of note, Abu Tailakh et al. 13 showed that patients with DM with high baseline HbA1c (>7%) were at higher risk of long-term complications and mortality after CABG. In patients with type 1 DM, high baseline HbA1c was associated with higher risks of long-term MACEs and death. 22 A meta-analysis showed that after coronary interventions, baseline HbA1c levels were associated with renal failure and myocardial infarction in patients with DM and with mortality and renal failure in those without DM. 15 Nevertheless, this meta-analysis also highlighted the lack of high-quality evidence. Another meta-analysis showed that the baseline HbA1c status was associated with morbidity and mortality after CABG, irrespective of DM status. 23 However, all these studies examined morbidity and mortality after CABG, but none specifically examined the patency of the grafts.  However, the same effect was not observed in the vein grafts. 27 In our study, the 1-year graft outcome was obviously better in artery grafts than in vein grafts, which was consistent with the previous findings. Besides, there was no difference in 1-year artery graft outcome between patients with HbA1c <6.5% and $6.5%. Thus, for patients with poor glycemic control, autologous arteries might be more appropriate as grafts for CABG, which would be a testable opinion in the future.
Our study found that, in both per-graft and per patient analysis, TþA significantly prevented vein graft failure (nonpatency or occlusion) at 1 year in the With nonpatency as outcome. b With occlusion as outcome.
A ¼ aspirin; CI ¼ confidence interval; HbA1c ¼ glycated hemoglobin; OR ¼ odds ratio, OR was adjusted for age, sex, medical history of hypertension and hyperlipidemia, SYNTAX score, target vessel distribution, antiplatelet therapy and statin use at 1-year after coronary artery bypass graft; SYNTAX ¼ synergy between percutaneous coronary intervention with Taxus and cardiac surgery; T ¼ ticagrelor.