The stakes are high in the quest to find the right treatment strategy. Cardiovascular disease is the leading cause of death among diabetics and the prevalence of diabetes is significant, estimated to be 2.8% of the population in 2000 and projected to to increase to 4.4% by 2030.
Cardiologists find these patients tend to have more advanced coronary artery conditions, frequently presenting with two and three-vessel disease, suggesting that PCI as the right strategy for treatment.
Yet studies consistently find that both non-insulin dependent and insulin-dependent diabetics have a poorer clinical outcome after PCI compared to non-diabetic patients. The authors of the benchmark Swedish Coronary Angiography and Angioplasty Registry describe the prognosis as ‘dismal’.
There is a greater tendency for restenosis, or reclosing of the artery, for diabetics after PCI. They have a higher risk of stent thrombosis and a greater need for returning to the operating table for another PCI revascularisation. Most significantly, diabetic patients have a higher incidence of death in the years following PCI.
A special session at EuroPCR 2011, Europe's largest congress for interventional cardiology, took up these clinical concerns during a review of clinical trials entitled Which Drug Eluting Stent for Diabetics?
The confidence of cardiologists in drug-eluting stents (DES) was shaken in 2008 by the landmark SYNTAX trial (SYNergy Between Percutaneous Coronary Intervention With TAXus and Cardiac Surgery) that included 452 diabetic patients among the 1,800 patients randomised between a minimally invasive stenting procedure and traditional coronary bypass surgery.
An editorial published in 2010 in the Journal of the American College of Cardiology, said the SYNTAX diabetes analysis did not tell clinicians to stop doing PCI in diabetic patients, but that it should only be done in patients in whom ‘there is no reasonable surgical option’.
JACC cautioned: ‘It is possible that a death penalty is not seen at one year but will appear at longer follow-up periods.’
Responding to these concerns, a second generation of DES was designed and the results from trials of these new stents were the focus of the EuroPCR 2011 session.
Multiple presentations were made for two DES that have emerged as favourites among the second-generation, the Xience V from Abbott Vascular and the Resolute from Medtronic. Both feature a polymer to bind a drug to the metal stent that is meant to prevent restenosis, but which cardiologists now suspect may be a cause of irritation that stimulates the reclosing of the artery.
Two relative newcomers presented during the session represented a third generation design using a biodegradable polymer, the Norobi from Terumo and the Titan from Hexacath.
Stent performance was discussed primarily in terms of what the board of EuroPCR called device-oriented criteria.
The good news is that modest progress has been made using these criteria for in-stent thrombosis or target vessel revascularisation, according to the take-home messages delivered by session co-chair, Upendra Kaul MD, Director of Cardiology at Fortis Escorts Heart Institute in New Delhi, India.
The use of second generation DES in diabetic patients yields consistently acceptable one- and two-year results with major adverse cardiac events in single digits, he said, despite the more challenging and complex cases diabetics present compared to non-diabetic patients.
But for patient-oriented criteria, which includes mortality after the procedure, the rate of death following PCI continues to be significantly higher for diabetic patients, especially those who are insulin-dependent.
A shared image among the presentations from manufacturers was the widening gap after four months between mortality for diabetic patients compared with non-diabetics.
While the two types of patients do equally well at first, there is a sudden slide in the incidence of death after that point, for reasons that are still not understood.
Sigmund Silber MD, from the Heart Catheterisation Centre in Munich, Germany, highlighted this frustrating phenomenon presenting a pooled analysis of clinical data on 867 diabetic patients who received a Resolute DES.
The analysis suggested an intriguing homogeneous treatment effect across diabetic and non-diabetic patients with consistently low rates of adverse events in this patient population at one year of follow-up, he said.
‘Not surprisingly, a notable exception to this effect was seen in the insulin-dependent diabetic patient, which serves to underscore the challenges that persist in determining the ideal interventional treatment for these patients,’ he said.