By Ehrin Armstrong
The recently published FREEDOM trial randomised 1,900 diabetic patients with multivessel coronary artery disease and stable angina to coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)2. At five years of follow-up, patients randomised to CABG had significantly lower mortality and myocardial infarction. These results were clinically meaningful, with an absolute event rate of the primary endpoint at five years of 18.7% in the CABG group and 26.6% in the PCI group.
Although FREEDOM was a well-designed multicentre international trial, the results are not generalisable to all patients with diabetes and coronary artery disease. Many diabetic patients have additional comorbidities, placing them at prohibitive risk of surgery. The majority of patients in the FREEDOM trial also had a normal left ventricular ejection fraction. Consistent with these limitations, only 10% of patients screened for FREEDOM met the study inclusion criteria, and almost half of those did not provide consent2.
Based on these results, patients with diabetes and symptomatic multivessel coronary artery disease who are candidates for surgery should undergo CABG as the preferred revascularisation option. PCI remains the preferred approach for diabetic patients with single vessel coronary artery disease, surgical contraindications, or high-risk acute coronary syndromes. Because FREEDOM included primarily first-generation drug-eluting stents, it is possible that the risk-benefit ratio may also favour PCI in certain diabetic patients where the risk of restenosis and target lesion failure could be minimised with newer drug-eluting stent technology.
PCI in diabetic patients
A number of factors should be considered among diabetic patients selected for PCI, including medical management, stent type, and secondary risk factor modification post-PCI.
Diabetic patients are at increased risk of restenosis and stent thrombosis relative to non-diabetic patients. However, recent studies with newer generation drug-eluting stent suggest that most of this excess risk is among patients who require insulin therapy for their diabetes3. It is unclear whether this increased risk of recurrent events is due to insulin, or whether insulin use is a marker for more significant disease. Regardless, the status of current medical therapy for diabetic patients should be assessed prior to PCI to better risk stratify patients.
Drug-eluting stents significantly reduce the rates of restenosis and need for repeat interventions among both diabetic and non-diabetic patients relative to bare metal stents. Comparisons of different drug-eluting stents types have suggested possible differences in outcomes among diabetic patients. In general, these results favour use of second-generation drug-eluting stents as compared to first generation drug-eluting stents4. In the USA, the zotarolimus-eluting Resolute stent (Medtronic) remains the only drug-eluting stents with a specific FDA indication for diabetic patients.
Optimal medical therapy after PCI in diabetic patients remains paramount. In addition to aspirin and statin therapy post-PCI, strong consideration should be given to more intensive antiplatelet therapy. In both the TRITON-TIMI 38 (prasugrel) and PLATO (ticagrelor) trials, diabetic patients derived greater benefit from more intensive antiplatelet therapy relative to clopidogrel5,6. In TRITON-TIMI 38, this benefit included a significantly lower risk of stent thrombosis among diabetic patients assigned to prasugrel.
Conclusion
Diabetes and coronary artery disease remains a challenging clinical problem. Recent trials focused on diabetic patients have helped emphasize the high-risk nature of this patient population. Future revascularisation strategies may hold promise for treatment of this challenging patient population.
Ehrin Armstrong is an interventional cardiologist from University of Colorado, Denver, USA
This commentary was written to support the American Diabetes Association’s Make the Link! Diabetes, Heart Disease and Stroke initiative. For more information, see: http://professional.diabetes.org/makethelink
References
1. Wild et al. Diabetes Care 2004; 27: 1047–53
2. Farkouh et al. The New England Journal of Medicine 2012; 367: 2375–84
3. Silber et al. JACC Cardiovasc Interv 2013; 6: 357–68
4. Stone et al. Circulation 2011; 124: 893–-900
5. Wiviott et al. Circulation 2008; 118: 1626–36
6. James et al. Eur Heart J 2010; 31: 3006–16
