Author + information
- Michael J. Domanski, MD∗ ( and )
- Michael E. Farkouh, MD, MS
- Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital/Mount Sinai Hospital, Toronto, Ontario, Canada
- Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada
- ↵∗Address for correspondence:
Dr. Michael J. Domanski, Division of Cardiology, Peter Munk Cardiac Centre, University Health Network/Mount Sinai Hospital, University of Toronto, 4N-484, 585 University Avenue, Toronto, Ontario M5G 2N2, Canada.
Substantial clinical trial data have accumulated comparing coronary artery bypass grafting (CABG) to percutaneous intervention (PCI) (1–4). These data consistently demonstrate the superiority of CABG over PCI in reducing long-term mortality and myocardial infarction (MI) in patients with stable but aggressive multivessel coronary artery disease (CAD). Aggressiveness of disease can be judged by extent/complexity (SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery] score) (1,2) or the presence of diabetes (3). CABG results in better outcomes than PCI in these patients, whether PCI is performed by balloon angioplasty alone, with bare-metal stents, or with drug-eluting stents.
Diabetes patients included in previous trials have primarily evaluated those with type 2 diabetes (T2DM). In this issue of the Journal, Nyström et al. (5) offers data specifically supporting CABG as the appropriate revascularization modality in patients with type 1 diabetes (T1DM).
Why is CABG the consistent “winner” in aggressive multivessel CAD regardless of the PCI procedure? Do we just need better stent platforms, or is there a fundamental difference in the physiological mechanism of benefit between these 2 revascularization procedures that favors CABG over PCI?
One consistent finding across studies comparing PCI with CABG is that the superiority of CABG is most pronounced when there is a greater degree of CAD complexity or disease aggressiveness.
The SYNTAX trial randomized 1,800 patients with 3-vessel or left main CAD to CABG or PCI (1,2). For the subgroup with 3-vessel disease, results after 5 years of follow-up showed that PCI resulted in a significantly higher rate of the composite endpoint of death, MI, or stroke (37.5% vs. 24.2%, respectively; p < 0.001) and long-term mortality in the 1,275 nondiabetic patients with multivessel CAD. In the SYNTAX trial, a scoring system (SYNTAX score) was used to categorize the extent and complexity of the CAD as low (≤22), intermediate (23 to 32), or high (≥33). The value of the SYNTAX score lies in its usefulness in predicting whether PCI or CABG is most likely to offer a better outcome for an individual patient. In fact, the 5-year results of the 3-vessel disease cohort in SYNTAX were dependent on lesion complexity as judged by the SYNTAX score, where patients with an intermediate or high (≥33) scores had significantly greater adverse cardiovascular events with PCI than CABG (6). Subsequently, the SYNTAX 2 scoring system, which accounts for both anatomy and patient characteristics, was developed and validated (7).
There are inherent differences in the pathophysiology of T1DM and T2DM, but both are strongly linked to the development of CAD and increased cardiovascular ischemic events (8).
The common link is that elevated plasma glucose results in an altered lipid profile, generation of reactive oxygen species, and reduced nitric oxide availability, triggering a cascade of pro-inflammatory and -thrombotic biochemical events, resulting in atherosclerosis and increased risk of MI (9).
The FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) (3) trial compared CABG to PCI with drug-eluting stents in patients with both diabetes (T1DM and T2DM) and multivessel CAD and showed that CABG is the revascularization procedure of choice in these patients. The benefit of CABG was driven by reductions in the rates of both MI (p < 0.001) and death from any cause (p = 0.049).
In patients with CAD and stable symptoms associated with diabetes or high SYNTAX score, the mechanisms of benefit of PCI and CABG are different, and this difference likely explains the superior results of CABG.
Arteries with 1 or more stenotic segments are known to have diffuse disease, including areas without significant lumen compromise. As a result, there is a nonzero probability of occlusion resulting in myocardial necrosis along the entire course of the artery; the risk at each point is a function of lesion characteristics (plaque structure and composition), the risk factor milieu (lipid level, smoking, and hemodynamics), individual predisposition (genetics), systemic disease (diabetes), and the presence of collaterals. Underscoring this point, the published data show that a coronary occlusion causing myocardial infarction is frequently not located where a prior coronary angiogram demonstrated severe stenosis in the artery. The overall risk that an occlusive event will cause myocardial damage is the sum of the risk at each point along the entire artery.
PCI opening of flow-restricting lesions reduces symptoms by improving perfusion. Although the treated area may have a reduced probability of a subsequent occlusive event, no reduction in probability of occlusion occurs in nonstented regions of the vessel—that is, in most of the artery. CABG also results in improved delivery of blood to myocardial regions whose flow is limited by vessel stenosis. However, when occlusion occurs proximal to the graft anastomosis to the native artery, regions distal to that occlusion are not rendered ischemic as they would have been following a PCI. So, a bypass graft that is in place distal to the site of an occlusive event prevents infarction of regions distal to the site of the occlusive event. This means that CABG removes large segments of the artery that would have added to the total risk of necrosis by an occlusion.
Better stents alone cannot change the superiority of CABG compared with PCI for patients with aggressive CAD (diabetes or high SYNTAX score), because PCI addresses only a small portion of the coronary anatomy. This does not diminish the importance of continuing advances in stent technology, but rather, it puts into appropriate perspective what can be expected from these advances (10).
The study by Nyström et al. (5) examined all patients with T1DM and multivessel CAD who underwent a first multivessel revascularization in Sweden from 1995 to 2013, and found that results for CABG were superior to those for PCI with respect to coronary heart disease mortality, myocardial infarction, and heart failure.
The study has a number of strengths. No randomized trial has compared revascularization strategies exclusively in patients with T1DM, so this paper provides information in an essentially data-free zone. However, the study also has several limitations. As an observational study, by its basic design it offers a chance of failure to balance recognized and unrecognized baseline differences between the study groups. Compared with the CABG group, patients in the PCI group were older; more often had cancer; and were more likely to have a history of stroke, heart failure, MI, or end-stage renal disease. In addition, the PCI group likely included patients who were not CABG candidates. In recent years, PCI has become the predominant approach, so that the control subjects in the study by Nyström et al. (5) are not really contemporaneous. This could also be explained by a number of mechanisms, including a better control of risk factors resulting in more focal CAD. This, however, is purely speculative.
The findings of this important study help to better inform practice, and should influence decision-making for revascularization in patients with T1DM.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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