Background
Diabetic patients have a higher prevalence of coronary artery disease (CAD) than the general population, manifesting as diffuse lesions and severe atherosclerosis in the left main artery and multiple other vessels [
1], severe symptoms often developing earlier in life combined with a substantially poorer prognosis than non-diabetic patients [
2,
3]. It has been reported that diabetes is considered a predictor of adverse events such as myocardial infarction (MI), repeat revascularization and cardiac death for patients who have undergone coronary artery bypass grafting (CABG) [
4‐
6].
For patients with prior CABG who require repeat revascularization, percutaneous coronary intervention (PCI) is usually the preferred strategy, rather than redo CABG, because of the low procedural mortality and similar long-term outcome [
7,
8], combined with placement o f a drug-eluting stent (DES) [
9]. Despite a number of studies investigating the impact that diabetes has on the clinical outcome of PCI with DES in patients without prior CABG [
10,
11], little is known about the influence of diabetes on outcomes of PCI with DES in patients who have previously undergone CABG.
In this study, we retrospectively assessed the clinical data of non-diabetic and diabetic patients with prior CABG who had subsequently received PCI with DES, aiming to establish the impact of DM on the long-term outcomes of PCI for restenosis after CABG.
Discussion
We performed a retrospective observational study to explore the outcomes of PCI with DES in diabetic vs non-diabetic patients who had previously undergone CABG in our single-center registry. We found that, compared to non-diabetic patients with prior CABG, subsequent PCI within the NCA with DES in diabetic patients appeared to result in a similar overall incidence of MACEs, cardiac death, MI, HF or repeated revascularization, extending our current understanding of the safety and efficacy of DES even in high-risk patients with prior CABG. This suggests that a DES may be considered the default option in these patient populations. In this study we also found that hypertension, prior HF, LVEF<50% and aspiration of thrombus are predictive of overall MACEs and patients taking statins are less likely to experience MACEs. Our results were based on matching propensity scores, which suggests that our findings are not due to negative confounding.
Diabetic patients with CAD are reported to have dysfunctional endothelial cells, increased atherosclerotic burden and fragile lipid-rich plaques [
15,
16], microcirculation disorder involving smaller vessels, and prothrombotic and proinflammatory states [
17,
18], which are related to progression of NCA disease. It is confirmed that CAD in diabetic patients appears as diffuse atherosclerosis with chronic total occlusion (CTO), opening and bifurcation lesions or multivessel disease and left main disease [
19], leading to fewer amenable options for re-intervention and suboptimal stent expansion [
8]. In this study, although the characteristics of the lesions in the NCAs relevant to ischemic territory are similar in both diabetic and non-diabetic patients, those in each group represent a high proportion of the CTO lesions, openings involving lesions, branches involving lesions or diffuse lesions. We consider that this is due to the combined CAD risk factors, such as hypertension, dyslipidemia, diabetes mellitus, fat, smoking and gender. In order to remove the influence of confounding CAD risk factors and to compare between the DM group and No DM group more precisely, we used the propensity score matching method, described in detail in the statistical analysis section.
Atherosclerosis is also reported to play an important role in later graft failure (graft age >6 months) [
8]. Graft atherosclerosis in diabetic patients has a larger necrotic core with unstable plaques [
20], which is friable and more prone to distal coronary embolization [
2]. Compared with non-diabetic patients with prior CABG, diabetic patients have a higher rate of graft stenosis and recurrent myocardial ischemic events [
21,
22], due to the progression of NCA disease or graft failure [
2]. In this study the majority of patients in each group had diseased grafts (81.2 and 79.2% in the No DM and DM groups, respectively), and a small proportion of the remaining patients in each group had myocardial ischema caused by isolated NCA lesions as a consequence of the progression of NCA disease (18.8 and 20.8% in the No DM and DM groups, respectively).
DES are superior to bare metal stents (BMS), in terms of their strut thickness and polymer coating composition, reducing repeat revascularization and in-stent thrombosis in addition to MI in non-diabetic patients [
19]. Published literature indicates that PCI with DES in diabetic patients compared with non-diabetic patients results in significantly higher mortality, reinfarction, and repeat revascularization for in-stent restenosis [
23‐
25]. The pathological mechanism of in-stent restenosis in diabetic patients is associated with excessive endothelial hyperplasia, vascular remodeling or increased platelet aggregation [
12]. However, in this study we found different results, especially when performing additional subgroup analysis of patients with PCI in only the NCA, in that PCI in the NCA with DES in diabetic patients compared with non-diabetic patients did not result in a high incidence of cardiac death, HF or repeat revascularization, and the incidence of MI between the two groups was not significantly different. However, one key observation should be clearly noted, that patients in that study included those without prior CABG. Conversely, all patients included in this study underwent prior CABG in our cardiac center, which could be considered a pretreatment for diabetic patients and functions as protection. In addition, all were high risk patients, especially in the DM group. They were older with a greater number of comorbidities and had severe NCA or graft lesions.
The studies of Ahmed [
26] and Ashfaq [
27] reported the influence of DM on outcomes in saphenous vein graft (SVG) stenting, with similar conclusions, that PCI with DES in diabetics resulted in long-term overall rates of MACEs, death, MI and repeat revascularization that were worse than in non-diabetics, quite different from Pendyala’s conclusion that diabetic patients undergoing SVG PCI had similar long-term outcomes [
12]. In the present study, after analysis of the whole study population (after matching,
n = 512), we found that the overall incidence of MACEs (DM: 37.5% vs No DM: 29.3%), principally driven by MI (DM: 18.4% vs No DM: 12.9%), were not statistically different between the two groups despite an increasing trend over time. Considering the conflicting data of all the patients that received PCI in the NCA and that a minority of patients were treated with PCI in both graft and NCA (No DM: 12.9% vs DM: 12.1), we performed further subgroup analysis of patients with PCI in only the NCA (
n = 635). We found that, compared to non-diabetic patients with prior CABG, subsequent DES in only the NCA of diabetic patients appeared to result in similar outcomes, such as rates of MACEs, cardiac death, MI, HF and repeat revascularization. Additional subgroup analysis of patients with PCI in both the NCA and graft, despite the small sample size of patients in this subgroup (
n = 89), demonstrated that, compared to non-diabetic patients with prior CABG, subsequent DES in the NCA and grafts of diabetic patients resulted in worse outcomes, consistent with Ahmed and Ashfaq’s studies. According to the 2018 ESC/EACTS Guidelines for myocardial revascularization [
2], it is recommended that PCI in the NCA should be considered rather than PCI in an SVG graft, because that is associated with a high risk of periprocedural MI [
28] and worse long-term outcomes such as all-cause death, MI or revascularization [
29] for no-reflow, subsequent in-stent restenosis, distant target lesions and excessive tortuosity [
8], especially for PCI in an SVG of a diabetic patient for graft atherosclerosis with a larger necrotic core and friable plaques [
20].
In this study, we also provided follow-up outcomes of patients with IR vs CR by PCI. Achieving CR of all significantly obstructed coronary artery has been an established goal of PCI, and more recent data demonstrate a salutary effect of CR following PCI on long-term outcomes. IR is associated with increased mortality following PCI, as well as with an increased incidence of MI, repeat revascularization, and MACCEs [
30]. Though, in our study the sample size of patients with IR was too small (5.1%), which would influence statistical results, we still believed that it made a little sense, compared with patients with CR, patients with IR were more likely to have MACEs (40.5%), cardiac death (8.1%) and MI (21.6%), though there were no significant difference between two groups. Further randomized controlled trial study with a larger sample size and longer follow-up may be required for patient with prior CABG.
Limitations
Firstly, this was a retrospective observational single-center study and so is subject to all the limitations of observational single-center studies, such as patient selection and a single therapeutic method, which might affect the results. Secondly, the angiography film results were analyzed by one cardiac surgeon and one cardiologist. Thirdly, the classification of graft lesions was in reference to the evaluation criteria of native vessels. Fourthly, the decision to perform PCI for each patient was taken by 2 operators, mostly based on an evaluation of the CAG results. Fifthly, 6 non-DM patients who had diabetes during the follow-up period were excluded from this study. Sixthly, we didn’t do PS matching for sub-group analysis. Despite these limitations, the results were derived from the largest angiographic study in patients with prior CABG so far published. In addition, the statistical analyses utilized rigorous methodology.
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