DRUG-ELUTING STENT SOLUTIONS: Treating Diabetics With Coronary Artery Disease
June 2005
What are the different types of diabetes?
There are two classic types of diabetes. Type 1 diabetes results from insufficient production of insulin by the pancreas and usually affects people at a young age. These diabetics tend to have very aggressive disease, systemic atherosclerosis and, as a result, often have a shortened life span. The vast majority of diabetics in the United States have type 2 diabetes, which presents at a later age, usually after age 40, and is commonly related to obesity. In type 2 diabetes, the pancreas produces enough insulin. However, due to a defect in the insulin receptors, the body cannot use it effectively so the blood sugar rises. As type 2 diabetics become more obese, they tend to have more fat cells, which make the insulin receptors less sensitive to insulin. In response, the pancreas makes more and more insulin up to a point at which it cannot produce insulin at all. Type 2 diabetes can be treated effectively with weight reduction or insulin sensitizers. However, some type 2 diabetics’ obesity and unresponsiveness require that they use insulin.
Why are diabetics more predisposed to CAD?
There are several reasons. The first is that diabetes has effects on the endothelial cell. Thus, they tend to have more activation and adhesion of platelets in response to any shear stress on the endothelial surface. They also tend to express more GPIIb/IIIa receptors, resulting in more aggregation of platelets. So, in general, the endothelial surface of their vasculature is more angry, or more responsive, than in non-diabetics
Diabetics also tend to have a more diffuse atherosclerotic pattern than non-diabetics. This is probably related to an increase in lipid-rich plaque. There is clearly an association between type 2 diabetes and hyperlipidemia. Since diabetics have a more diffuse atherosclerotic pattern, they often have more advanced disease upon presentation. Furthermore, they often have autonomic dysfunction and therefore cannot sense chest pain as well as non-diabetics, so they often present very late with aggressive disease. A number of these patients have silent ischemia, impaired coronary flow reserve (the difference between normal blood flow and the increased blood flow that occurs when the blood vessels dilate) and reduced ability to handle embolization. Finally, diabetics probably have a higher response to any kind of injury to the endothelial cell; therefore, even by spontaneous plaque rupture, they have a more exuberant healing response. They heal more aggressively after angioplasty or stenting, resulting in an approximately 8 to 10 percent increase in restenosis over non-diabetics for any degree of lesion length or vessel size. There is definitely a price to be paid in the cath lab for any patient who has diabetes.
What are the differences between type 1 and type 2 diabetics who have CAD?
In nondiabetics, antiproliferative agents like sirolimus and paclitaxel block a specific cellular pathway that mediates restenosis. However, in patients with very advanced type 2 diabetes requiring insulin, it is theorized that there is another, unique pathway by which drugs like paclitaxel work. This theory needs more thorough evaluation, but there is some interest, at least on the basic scientific level, in a unique mechanism by which the restenotic process occurs in diabetics who require insulin.
With all of these challenges, how do you determine a treatment strategy for patients with diabetes?
That’s a good question. Historically, most of the interventional community has treated diabetics with multivessel disease with bypass surgery. This is based on a number of fairly large, randomized trials, the most important being the Bypass Angioplasty Revascularization Investigation (BARI) trial, which studied balloon angioplasty versus bypass for the treatment of multivessel disease. Although there was no difference in mortality or myocardial infarction in the non-diabetic group of this trial, there was a significant benefit to performing bypass in the diabetic group.
Today, in the era of DES, with more effective means of treating diabetics, there has been a shift away from bypass and towards more percutaneous approaches to angioplasty. We really do not know the best way to treat diabetic patients with CAD, but we will obtain a more definitive answer from the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial, a randomized trial supported by the National Institutes of Health and the National Heart, Lung and Blood Institute. The FREEDOM trial is evaluating over 1,000 diabetic patients to determine whether bypass or DES is a more effective treatment for CAD. Unfortunately, we won’t know the outcome of this trial for three to five years.
If a patient has diffuse bifurcation disease involving many vessels and associated with some chronic total occlusions, I think bypass is still their best option until we have either better treatment strategies or more firm data. However, if a diabetic patient has lesions that are amenable to intervention or relatively discrete perhaps two or three lesions and not six or seven it makes sense to perform percutaneous intervention. You really don’t take away the option for surgery if you do angioplasty in some proximal vessels in diabetics. With secondary prevention measures that include aggressive reductions of lipids, optimum glucose control and the addition of angiotensin converting enzyme (ACE) inhibitors, beta-blockers and aggressive-dose statins, these patients can do very well. Furthermore, we have strong data for both the TAXUS Stent and the Cypher Stent suggesting 50 to 80 percent reductions in clinical restenosis rates compared to bare-metal stents. In my opinion, DES offer the best option for managing moderate diabetic atherosclerotic coronary disease.
What is important for cath lab staff to understand about diabetic patients?
Diabetic patients are a particular challenge for cath lab staff because, in general, their vessels are smaller. In many small vessels, there may be some remodeling, so the vessel wall is relatively thick but the lumen is still preserved to some degree. Although the vessel appears small angiographically, intravascular ultrasound will reveal the true lumen diameter to be substantially larger and will confirm the presence of extensive diffuse disease. With diabetics, in addition to proximal ischemic disease, we also see a very diffuse distal disease that can be effectively treated only with medication or, in advanced stages, perhaps coronary bypass surgery.
Cath lab staff should also be aware of the increasing prevalence of diabetes, primarily due to the obesity epidemic we are now facing. In the United States, the prevalence of diabetes is increasing by 15 to 20 percent per decade. That’s a pretty dramatic increase. In some DES trials studying more complex lesions smaller vessels and longer lesions we actually see the diabetic population above 30 percent. This is a significant portion of the population arriving in our cath labs.
Cypher is a trademark of Cordis Corporation.
Sponsored by Boston Scientific.
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