The optimal revascularization modality in patients with multivessel CAD has been a source of debate for decades in patients with diabetes, and this debate is expected to continue with the new era of DESs and antithrombotic and antiplatelet therapies. In this section, we consider studies that have addressed the issue of revascularization in patients with diabetes with multivessel CAD (PCI vs. CABG). Tables 21.3 and 21.4 summarize the results from RCTs, meta-analyses, and registries.

The SYNTAX RCT compared PCI (paclitaxel-eluting stent [PES]) versus CABG in a study population of 1800 patients with left main and/or multivessel CAD. The results were statistically not different in terms of the primary composite endpoint at 1 year (death, stroke, MI) between both revascularization methods in patients without diabetes (6.8% CABG vs. 6.8% PES, P =.97) and patients with diabetes (10.3% CABG vs. 10.1% PES, P =.96). However, in subgroup analyses, mortality was higher after PES in patients with diabetes and highly complex lesions (13.5% PCI vs. 4.1% CABG, P =.04), and PES resulted in higher target-vessel revascularization (TVR) in patients with diabetes (20.3% vs. 6.4% CABG, P >.001). The SYNTAX follow-up at 3 years showed that patients with diabetes treated initially with PCI-PES experienced a higher risk of MACEs (37.0% PES vs. 22.9% CABG, P = .002) or repeat revascularization (28.0% PES vs. 12.9% CABG, P < .001) compared with the CABG-treated group. After exclusion of the clinically less impactful TVR component endpoint, the composite endpoint of death, stroke, and MI was not statistically different between the groups (16.3% for PCI vs. 14.0% for CABG, P =.53). The authors concluded that PCI might be preferred for patients with less complex left main and/or three-vessel lesions (SYNTAX scores ≤22), but CABG should be the option of choice for patients with more complex left main CAD or three-vessel anatomic disease, especially for patients with diabetes. The 5-year follow-up from the overall population has been published, and results confirmed that CABG should be the choice for patients with complex lesions (intermediate and high SYNTAX scores) and that PCI is an acceptable treatment for less complex lesions (low SYNTAX scores).

The FREEDOM RCT compared PCI (DES) with CABG in 1900 patients with diabetes with multivessel CAD and showed an increased risk of the primary outcome of MACEs in the PCI group compared with the CABG group after 5 years of follow-up (26.6% vs. 18.7%, P = .005). CABG was superior to PCI in terms of a reduced overall death rate (16.3% vs. 10.9%, P = .049) and MI (13.9% vs. 6.0%, P < .001) but inferior to PCI in terms of a higher rate of stroke at 5 years (2.4% in the PCI group and 5.2% in the CABG group, P = .03). However, debate persists because the PCI option yielded comparable results to CABG during the first 2 years of follow-up, with event curves thereafter diverging ultimately to reveal an absolute 5-year survival benefit of 5.4% for CABG (95% CI, 1.5–9.2). Fig. 21.3 summarizes the findings of the 5-year follow-up of the SYNTAX and FREEDOM trials in patients with diabetes according to the baseline anatomic complexity. Both studies reported a benefit of treatment with CABG in patients with complex disease (SYNTAX score ≥33 points) in terms of composite endpoint reduction (death, stroke, MI). In patients with less complex disease (SYNTAX score <22 points), PCI and CABG results did not differ significantly, suggesting that PCI is an acceptable alternative. In patients with intermediate disease (SYNTAX score 23–32 points), the FREEDOM trial reported a benefit of CABG not confirmed in the SYNTAX trial, suggesting that a consensus for the optimum treatment should be discussed by the “heart team,” including both cardiac surgeons and interventional cardiologists.

Five-year outcomes of patients with diabetes according to the anatomic lesion complexity (SYNTAX score) and revascularization treatment (PCI vs. CABG). Binary event rates of the composite endpoint of death, stroke, and myocardial infarction in the SYNTAX53 and FREEDOM trials. CABG , Coronary artery bypass grafting; PCI , percutaneous coronary intervention. * P < .05.

In the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL Trial), the 3-year composite primary endpoint (composite of all-cause death, stroke, or MI) was significantly higher in patients with compared to those without diabetes (20.0% vs. 12.9%; P <.001). The rate of the 3-year primary endpoint was similar after treatment with PCI and CABG in patients with diabetes (20.7% vs. 19.3%; HR, 1.03; 95% CI, 0.71–1.50; P =.87) and without diabetes (12.9% vs. 12.9%; HR, 0.98; 95% CI, 0.73–1.32; P =.89).

In current practice, patients with diabetes and multivessel CAD deemed to be at a standard surgical risk based on comorbidities and coronary anatomy should be informed about the potential survival benefit with CABG as well as the lower need for repeat revascularization and MI. This shared-decision discussion at this stage is aimed at offering patients the most appropriate and evidence-based treatment recommendations with all the transparency of the available current evidence. Overall, the revascularization strategy should be based on and guided by anatomic and clinical characteristics, as well as an interventional SYNTAX score ( http://syntaxscore.com ) and surgical EUROSCORE ( www.euroscore.org ) reflecting the complexity and its influence on anticipated results from each revascularization modality and its risks. Recently, the SYNTAX II score has been developed and estimates the 4-year mortality for each treatment (PCI vs. CABG). The score contains eight variables: anatomic SYNTAX score, age, creatinine clearance, left ventricular ejection fraction, presence of unprotected left main CAD, peripheral artery disease, female sex, and chronic obstructive pulmonary disease. Although the impact of newer-generation DESs needs to be fully evaluated, the threshold for CABG should be definitively lower in patients with diabetes than in their nondiabetic counterparts.

In the 2019 European Society of Cardiology (ESC) myocardial revascularization guidelines, PCI was the preferred approach for patients with diabetes with multivessel disease and low complex CAD defined as a SYNTAX score equal or less than 22 points, including patients with left main disease (class I). In a recent meta-analysis of 4394 patients (also without diabetes) with left main CAD at low or intermediate CAD complexity (median SYNTAX score 25 points), the 5-year all-cause death was similar between PCI and CABG. Whereas PCI is a valuable option in a patient with one- or two-vessel CAD, including left main disease, CABG remained the favored approach of revascularization in diabetes patients with three-vessel CAD at low complexity.

In the 2021 US revascularization guidelines, CABG with an arterial graft on the left anterior descending artery is recommended in preference to PCI to reduce mortality and repeat revascularizations in patients with diabetes and multivessel CAD (Class of Recommendation I, Level of Evidence A). In patients amenable to PCI who have an indication for revascularization and are poor candidates for surgery, PCI can be useful to reduce long-term ischemic outcomes (Class of Recommendations 2a, Level of Evidence B). In patients with diabetes who have left main stenosis and low- or intermediate-complexity CAD in the rest of the coronary anatomy, PCI may be an alternative to CABG to reduce major adverse cardiovascular events (Class of Recommendations 2b, Level of Evidence B).

In patients with intermediate or high complex CAD defined as SYNTAX score more than 22 points, the recommended approach for revascularization is in general CABG over PCI. Independent of the degree of complexity of CAD, PCI remains the best option, if technically feasible, in high-surgical-risk patients.

The treatment choice should ultimately be based on the patient’s concerns and preferences after a discussion within a multidisciplinary heart team, including but not limited to an interventional cardiologist and a cardiac surgeon.

Current international guidelines on coronary revascularization recommend the use of newer-generation DESs over BMSs in patients with an indication for PCI, irrespective of clinical presentation, coronary lesion anatomy, comorbidities, or diabetic status. Newer-generation DESs have been shown to reduce the risk for repeat revascularization, while maintaining similar risks of all-cause death, MI, or ST, compared to BMSs among patients with DM (X). The clinical benefits of newer-generation DESs are, however, hampered by the persistent higher risk for stent-related adverse events and patient-oriented adverse outcomes after PCI, in particular restenosis and the need for new target-lesion revascularization (TLR), in patients with diabetes compared to their nondiabetic counterparts (X), regardless of the underlying CAD complexity.

Table 21.5 summarizes the main studies testing different types of stents for PCI for all-comer patients including in patients with diabetes. The optimal DES choice for PCI in diabetic individuals remains uncertain. In a study-level meta-analysis including 8095 patients from 18 RCTs, second-generation DESs with thin-strut stent platforms eluting zotarolimus (ZES) or everolimus (EES) from durable biocompatible polymer coatings were shown to reduce by 30% the risk of TLR and by 46% the risk of ST compared with first-generation thicker-strut durable polymer DESs among patients with diabetes undergoing PCI.

Table 21.5

Studies Comparing Different Drug-Eluting Stents in Patients with Diabetes

TRIAL	YEAR	NUMBER	MAXIMUM FOLLOW-UP	MORTALITY	TLR	MACEs	ST
RCTs Comparing Different DESs in Patients With Diabetes
SESs vs. PESs
DES-DIABETES	2008	400	9 months	0% vs. 0.5%	2.0* vs. 7.5%*	2.0% vs. 8.0%*	0.5% vs. 0%
DES-DIABETES	2010	400	48 months	3.0% vs. 5.0%	7.5% vs. 12.0%	11.0% vs. 16%	4% vs. 1.5%
DiabeDES	2009	153	8 months	2.6% vs. 1.3%	6.5% vs. 11.8%	7.9% vs. 14.5%	0% vs. 2.6%
Hong et al.	2010	169	36 months	3.5% vs. 2.4%	2.4% vs. 7.1%	5.9% vs. 9.5%	1.2% vs. 3.6%
Kim et al.	2008	169	6 months	1.2% vs. 1.2%	2.4% vs. 4.8%	NA	NA
Naples-DIABETES	2011	151	36 months	6.6% vs. 4.0%	2.6% vs. 9.3%	13.2% vs. 1w7.5%	1.3% vs. 0%
SIRTAX	2008	201	24 months	8.3% vs. 10.8%	7.4% vs. 17.2%*	14.8% vs. 25.8%*	0.9% vs. 3.2%
ZESs vs. PESs
ENDEAVOR IV	2009	477	12 months	0.0% vs. 0.9%	6.9% vs. 5.8%	6.9% vs. 7.2	0.9% vs. 0.4%
Naples-DIABETES	2011	150	36 months	5.3% vs. 4.0%	18.7% vs. 9.3%	35.6% vs. 17.5%*	4.0% vs. 0%
ZESs vs. SESs
Naples-DIABETES	2011	151	36 months	5.3% vs. 6.6%	18.7% vs. 2.6%	35.6% vs. 13.2%*	4.0% vs. 1.3%
SORT-OUT III	2011	337	18 months	8.3% vs. 5.4%	12.4% vs. 1.2%*	18.3% vs. 4.8%*	1.8% vs. 0.0%
EESs vs. SESs
ESSENCE-DIABETES	2011	300	12 months	1.3% vs. 3.3%†	0.7% vs. 2.6%†	2.0% vs. 5.3%†	0.7% vs. 0.7%†
EESs vs. PESs
SPIRIT IV	2010	1185	12 months	1.6% vs. 0.8%†	4.2% vs. 4.7%	6.4% vs. 7.1%	0.8% vs. 1.3*
Pooled Data Analyses Comparing Different DES in Patients With Diabetes
SESs vs. PESs
Mahmud et al.	2008	2422	12 months	NA	7.6% vs. 8.6%	12.9% vs. 15.4%	0.6% vs. 1.5%*
Stettler et al.	2006	5455 person-years		NA	RIRR 0.86 (0.40–1.86)	RIRR 0.86 (0.21–1.71)	NA
Kufner et al.	2011	1183	48 months	HR 1.04 (95% CI 0.74–1.45)	HR 0.66 (95% CI 0.47-0.91)	NA	HR 1.00 (95% CI 0.31–3.30)
				Mortality	TLR	MI	ST
Stettler et al.	2008	3852	NA	HR 0.95 (95% CI 0.63–1.43)	NA	HR 0.80 (95% CI 0.55–1.27)	HR 0.20 (95% CI 0.02–1.04)
PESs vs. SESs
Bangalore et al.	2012	22,855 patient years		HR 0.97 (95% CI 0.71–1.32)	HR 1.36 (95% CI 1.05 vs. 1.82)*	HR 1.16 (95% CI 0.80–1.64)	HR 1.23 (95% CI 0.74–2.17)
EESs vs. SESs
Bangalore et al.	2012	22,855 patient years		HR 0.83 (95% CI 0.45–1.41)	HR 0.81 (95% CI 0.46–1.27)	HR 0.74 (95% CI 0.32–1.46)	HR 0.85 (95% CI 0.36–2.02)
EESs vs. PESs
Stone et al.	2011	1869	24 months	3.9% vs. 2.9%	5.5% vs. 6.1%	4.2% vs. 4.9%	1.6% vs. 2.0%
Bangalore et al.	2012	22,855 patient years		HR 0.86 (95% CI 0.47–1.45)	HR 0.60 (95% CI 0.33–0.93)	HR 0.64 (95% CI 0.28–1.19)	HR 0.69 (95% CI 0.29–1.55)

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