PCI or CABG in Stable Patients With Multivessel CAD and Diabetes

Introduction

Cardiac revascularization in patients with stable coronary artery disease (CAD) is an important therapeutic intervention for the improvement of symptoms and prognosis. Prior to revascularization, patients must receive guideline-recommended medical therapy due to its established benefits.1,2 Also notable is that the best current revascularization results achieved with percutaneous coronary intervention (PCI) are with new-generation drug-eluting stents (DES) and for coronary artery bypass grafting (CABG) with maximal use of arterial grafts.1,2 The multitude of studies for revascularization comparing PCI and CABG cannot provide a single solution for the entire spectrum of patients with stable CAD. Nevertheless, CABG results in more complete revascularization than PCI, particularly in complex multivessel CAD, which often is observed in patients with diabetes.

Diabetes and CAD

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. This condition is classified as either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), depending on the underlying pathophysiology. T1DM, usually characterized by onset at an early age, is an autoimmune-mediated destruction of insulin-producing islet beta cells in the pancreas that eventually leads to a loss of insulin secretion. T2DM, often characterized by adult onset, is due to insulin resistance and, consequently, a slow progression to hyperglycemia. Patients with diabetes have an increased risk for cardiovascular (CV) disease, and the risk for CAD is increased two- to fourfold compared with people without diabetes (this is even higher in patients with T1DM.3 In diabetes, risk factors such as hyperglycemia, dyslipidemia, hypertension, kidney failure, and overweight (especially seen in T2DM) are all important contributing factors to the increased risk and complexity of CAD. Patients with diabetes have accelerated atherothrombosis with an early onset of atherosclerosis suggested to be more diffuse and more extensively involved and with an increased risk of progression of coronary atherosclerosis compared with patients without diabetes.4,5 In patients with diabetes, coronary angiography often reveals complex multivessel CAD, an important challenge for the multidisciplinary heart team that has to discuss and decide, together with the patient, the best revascularization options in the light of current guidelines.1,2

Revascularization in Diabetes

Approximately 25% of all patients who undergo multivessel revascularization have diabetes. A number of studies have demonstrated that CABG should be the preferred strategy for multivessel revascularization in patients with diabetes. In this group, CABG leads to improved survival rates and a reduced risk of myocardial infarction and repeat revascularization compared with revascularization with PCI.1,2 In the BARI (Bypass Angioplasty Revascularization Investigation) trial, a subset of 353 patients with diabetes who underwent PCI had almost a doubled 5-year mortality compared with those who underwent CABG.6 However, if only saphenous vein grafts were used as conduits, cardiac mortality was similar to that with PCI, demonstrating the importance of arterial grafting.6 It was further demonstrated in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) study that among patients with diabetes, prompt revascularization by CABG significantly reduced major CV events compared with intensive medical treatment alone. In contrast, there was no difference in CV events between patients who underwent PCI and patients who received only intensive medical treatment.7

The first randomized study of coronary revascularization in patients with diabetes, the CARDia (Coronary Artery Revascularization in Diabetes) trail, comprising 510 patients, did not show any significant superiority for CABG compared with PCI; however, the study was underpowered for such a statement.8 This was also the case for the VA CARDS (Coronary Artery Revascularization in Diabetes) trial, which was stopped prematurely due to slow recruitment; no firm conclusion about the comparative effectiveness between PCI and CABG was possible.9 The first study to clearly demonstrate that CABG should be the preferred strategy of revascularization in patients with diabetes and multivessel disease was the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial, where 1,900 patients with diabetes and multivessel disease were randomized to undergo either PCI or CABG. Patients who underwent CABG compared with PCI had a reduced risk of the composite outcome of death from any cause, nonfatal myocardial infarction, or nonfatal stroke during 5 years of follow-up.10 Similarly, in a subgroup analysis of 452 patients with diabetes who were randomized to either PCI or CABG in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) trial, a survival benefit was found for patients treated with CABG.11 A recently published meta-analysis from 8 trials, comprising 3,612 patients with diabetes and multivessel stable CAD, compared revascularization by PCI or CABG in terms of all-cause mortality.12 At 5-year follow-up, patients allocated to CABG had lower all-cause mortality than those allocated to PCI, and there were no differences in outcome observed whether PCI stenting was done with bare-metal stents or DES.12 Taking all randomized studies together, there is to date no study that suggests a survival advantage of PCI over CABG in patients with diabetes and multivessel CAD.

Because 90% of all patients with diabetes have T2DM, the results from the abovementioned studies may not be generalized to patients with T1DM because the type of diabetes (T1DM or T2DM) has not been reported. Type of diabetes may be of great importance because long-term prognosis after CABG is dire in patients with T1DM compared with patients with T2DM who have a similar long-term prognosis as patients without diabetes (Figure 1).13 The reason for the poorer prognosis in T1DM after CABG is not fully understood; other comorbidities such as chronic kidney disease, peripheral artery disease, and heart failure, as well as diabetes duration and glycemic control may to some extent explain the dire prognosis observed in T1DM.13 Because diabetes duration in general is much longer in patients with T1DM, the exposure time to hyperglycemia is essential. Long-standing hyperglycemia induces inflammation in the vessel wall, promoting atherosclerosis, and abnormal vascular findings (e.g., earlier onset, higher degree, and more disseminated and aggressive) are much more common in patients with T1DM compared with individuals without diabetes.14 In two recent Swedish nationwide observational cohort studies, we demonstrated that in patients with diabetes, poor glycemic control prior to CABG is associated with an increased risk of death or major CV events (MACE).15,16 This association was even more pronounced in patients with T1DM, demonstrating a relationship between hemoglobin A1c (HbA1c) and death or MACE already at HbA1c levels 7.1-8%, which was further increased by 18% for every 1% absolute increase in HbA1c levels (Figure 2).16

Figure 1

Figure 1
This figure shows the age-adjusted cumulative survival curves in 39,235 patients (no diabetes: n = 30,302; T1DM: n = 725; T2DM: n = 8,208) who underwent primary isolated CABG in Sweden between 2003 and 2013.13

Figure 2

Figure 2
This figure shows the relationship between pre-operative HbA1c level and all-cause mortality or a MACE. The graph shows the adjusted hazard ratio (solid line) and 95% confidence intervals (dashed lines) for the association between baseline HbA1c and combined all-cause mortality and MACE occurrence. The baseline HbA1c level was modeled with restricted cubic splines with 3 knots (at 7.1, 8.5, and 9.8%) in a Cox regression model. The reference level was set at 7.0% for the estimation of hazard ratios. The Cox model was adjusted for age and sex.16

Because no randomized clinical trial, such as the FREEDOM trial, has investigated patients with T1DM, the recommendation that all patients with diabetes in the need of multivessel revascularization should undergo CABG cannot easily be translated into patients with T1DM. Therefore, our group recently investigated, in an observational study, all patients with T1DM in Sweden from 1995 to 2013 who underwent a first multivessel revascularization with either CABG or PCI.17 During the study period, 2,546 patients with T1DM underwent a first multivessel revascularization (PCI = 1,863 vs. CABG = 683). With a mean 10.6 years of follow-up, the absolute risk of death was higher at 1 year (5.0 vs. 0.7%), 2 years (8.3 vs. 1.2%), and 5 years (18.6 vs. 6.4%) after revascularization in patients who underwent PCI compared with CABG. However, the risk of death after adjustment for differences between groups was similar in the PCI group compared with the CABG group (hazard ratio 1.14; 95% confidence interval, 0.99-1.32) (Figure 3). On the other hand, cause-specific mortality showed that patients who underwent PCI were more likely to die from CAD than patients who underwent CABG (hazard ratio 1.36; 95% confidence interval, 1.13-1.64). After revascularization, the absolute risks at 1 year, 2 years, and 5 years for myocardial infarction, heart failure, stroke, and repeat revascularizations were consistently higher in patients who underwent PCI compared with CABG, with the largest difference found for repeat revascularizations.17 We doubt that a large randomized study, such as the FREEDOM trial, can be conducted with patients with T1DM to give a definitive answer for the best method of revascularization in these patients. Because results from our observational study are consistent with those of the FREEDOM trial, it may influence decision-making for revascularization in patients with T1DM.18

Figure 3

Figure 3
This figure shows the cumulative all-cause mortality survival curves in patients with T1DM with multivessel disease who underwent revascularization by CABG (n = 683) or PCI (n = 1,863) from 1995 to 2013 in Sweden.17

Conclusions

People with diabetes have an increased risk for CAD compared with people without diabetes. Coronary angiography often reveals complex multivessel CAD in patients with diabetes, addressing an important challenge for the best revascularization options, in which strong evidence supports the use of CABG over PCI.1,2 Because most of the trials comprise patients with T2DM, current guidelines cannot easily be supported for patients with T1DM. We have, in serial observational studies, demonstrated that patients with T1DM have a dire prognosis after CABG compared with patients with T2DM13 and that preoperative glycemic control is of great importance for the outcome in patients with diabetes.15,16 Finally, we have now demonstrated that CABG is superior over PCI in patients with T1DM with multivessel CAD; these results can be used to guide decisions on the best revascularization options for these patients.

References

  1. Authors/Task Force members, Windecker S, Kolh P, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35:2541-619.
  2. Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014;64:1929-49.
  3. Rawshani A, Rawshani A, Franzén S, et al. Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes. N Engl J Med 2017;376:1407-18.
  4. Roffi M, Angiolillo DJ, Kappetein AP. Current concepts on coronary revascularization in diabetic patients. Eur Heart J 2011;32:2748-57.
  5. Iijima R, Ndrepepa G, Kujath V, et al. A pan-coronary artery angiographic study of the association between diabetes mellitus and progression or regression of coronary atherosclerosis. Heart Vessels 2017;32:376-84.
  6. Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease: the Bypass Angioplasty Revascularization Investigation (BARI). Circulation 1997;96:1761-9.
  7. BARI 2D Study Group, Frye RL, August P, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009;360:2503-15.
  8. Kapur A, Hall RJ, Malik IS, et al. Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial. J Am Coll Cardiol 2010;55:432-40.
  9. Kamalesh M, Sharp TG, Tang XC, et al. Percutaneous coronary intervention versus coronary bypass surgery in United States veterans with diabetes. J Am Coll Cardiol 2013;61:808-16.
  10. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367:2375-84.
  11. Kappetein AP, Head SJ, Morice MC, et al. Treatment of complex coronary artery disease in patients with diabetes: 5-year results comparing outcomes of bypass surgery and percutaneous coronary intervention in the SYNTAX trial. Eur J Cardiothorac Surg 2013;43:1006-13.
  12. Verma S, Farkouh ME, Yanagawa B, et al. Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol 2013;1:317-28.
  13. Holzmann MJ, Rathsman B, Eliasson B, et al. Long-term prognosis in patients with type 1 and 2 diabetes mellitus after coronary artery bypass grafting. J Am Coll Cardiol 2015;65:1644-52.
  14. de Ferranti SD, de Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care 2014;37:2843-63.
  15. Kuhl J, Sartipy U, Eliasson B, Nyström T, Holzmann MJ. Relationship between preoperative hemoglobin A1c levels and long-term mortality after coronary artery bypass grafting in patients with type 2 diabetes mellitus. Int J Cardiol 2016;202:291-6.
  16. Nyström T, Holzmann MJ, Eliasson B, Kuhl J, Sartipy U. Glycemic Control in Type 1 Diabetes and Long-Term Risk of Cardiovascular Events or Death After Coronary Artery Bypass Grafting. J Am Coll Cardiol 2015;66:535-43.
  17. Nyström T, Sartipy U, Franzén S, et al. PCI Versus CABG in Patients With Type 1 Diabetes and Multivessel Disease. J Am Coll Cardiol 2017;70:1441-51.
  18. Domanski MJ, Farkouh ME. Type 1 Diabetes, Coronary Disease Complexity, and Optimal Revascularization Strategy. J Am Coll Cardiol 2017;70:1452-54.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Heart Failure, Cardiac Surgery and SIHD, Acute Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Hypertension, Chronic Angina

Keywords: Angioplasty, Atherosclerosis, Blood Glucose, Cardia, Comorbidity, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Decision Making, Diabetes Mellitus, Diabetes Mellitus, Type 2, Drug-Eluting Stents, Dyslipidemias, Hemoglobin A, Glycosylated, Heart Failure, Hyperglycemia, Hypertension, Inflammation, Insulin Resistance, Insulins, Myocardial Infarction, Myocardial Revascularization, Overweight, Percutaneous Coronary Intervention, Peripheral Arterial Disease, Prognosis, Renal Insufficiency, Renal Insufficiency, Chronic, Risk Factors, Saphenous Vein, Stroke, Survival Rate, Taxus, Angina, Stable


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