Treating multivessel CAD in diabetic patients William E. Lawson, MD

Although most interventional cardiologists are familiar with the results of the Bypass Angioplasty Revascularization Investigation (BARI) randomized clinical trial and the subsequent National Heart, Lung, and Blood Institute Clinical Alert, as Martin and McGuire explain (page 14), there is still no consensus regarding the optimal treatment strategy for revascularization in diabetic patients with multivessel coronary artery disease (CAD). It remains a hot-button topic of debate at many cardiac catheterization conferences. Why do so many of these patients undergo angioplasty as the preferred treatment despite the decreased mortality demonstrated for surgical revascularization compared with angioplasty in BARI? Were there issues with data collection and analysis? The results for the diabetic patients in BARI were from a post hoc subgroup analysis rather than a prespecified analysis. Although the results showed a 7-year cardiac mortality benefit in patients with diabetes who underwent coronary artery bypass graft (CABG) surgery compared with those who underwent percutaneous transluminal coronary angioplasty (PTCA; 23.6% versus 44.3%), on further analysis, this benefit applied only to those receiving a left internal mammary artery graft, not to those only receiving saphenous vein grafts.1 Those who underwent CABG surgery with a left internal mammary artery graft had a mortality rate of 16.8% compared with 44.5% for those who received only saphenous vein grafts and for those who underwent percutaneous coronary intervention (PCI).

Are the results still relevant? As with any trial that takes years to perform, the practice of both surgery and angioplasty has changed substantially since BARI was completed. Angioplasty has changed to include the routine use of new antiplatelet agents, glycoprotein (GP) IIb/IIIa receptor blockers, HMG-CoA reductase inhibitors (statins), bare metal stents and drug-eluting stents, and brachytherapy. Tight glycemic control has been shown to have an important influence on restenosis in diabetic patients.2 The GP IIb/IIIa receptor blockers have improved angioplasty outcomes, particularly in patients with diabetes. Diabetic patients with multivessel CAD undergoing stenting with the GP IIb/IIIa receptor blocker abciximab had a significant reduction in 1-year mortality from 7.7% to 0.9% in an analysis of data pooled from the Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial, the Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) trial, and the Evaluation of IIb/IIIa Platelet Inhibitor for Stenting (EPISTENT) trial.3 Insulin-dependent diabetic patients treated with abciximab had a significant decrease in mortality from 8.1% to 4.2%.

The Achilles’ heel of angio-

plasty and stenting—restenosis—has largely succumbed to prevention with drug-eluting stents and treatment with brachytherapy. The Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) trial demonstrated an 83% reduction in in-stent restenosis in diabetic patients with Ir-192 therapy.4 In BARI, 54% of PTCA patients underwent repeat revascularization compared with 8% of those treated with CABG surgery. In the Arterial Revascularization Therapy Study (ARTS), however, for patients who underwent multivessel revascularization with stents, the repeat revascularization rate decreased to 21.2% at 1 year and 26.7% at 3 years compared with 3.8% and 6.6%, respectively, in patients randomly assigned to CABG surgery.5 In the Sirolimus-coated Bx Velocity Balloon-expandable Stent in the Treatment of Patients with De Novo Coronary Artery Lesions (SIRIUS) study, the revascularization rate decreased even further to 6.4% at 9 months.

Do the results apply to your practice? The results of bypass surgery in your hospital may differ significantly from the results reported in BARI. The immediate results may not be as good, the left internal mammary artery may not be used routinely to bypass the left anterior descending artery, or saphenous vein grafts may be used exclusively. Other issues may also apply. The patient may refuse surgical revascularization in favor of multivessel stenting. Poor documentation often makes the cardiologist suspect of self-referral when this occurs. The choice of revascularization certainly has a major and easily measured impact on the cardiologist’s (and the cardiothoracic surgeon’s) income. Professionalism in the context of procedural self-referral has become an issue for national health care policy makers. Payer input may yet have decisive input into revascularization practices. The Centers for Medicare and Medicaid Services have set a goal of “paying for quality” and are examining processes and outcomes to achieve this objective. Managed care and industry are embracing similar objectives in the Leapfrog initiative.

Will drug-eluting stents make a difference? The available data suggest a 70% reduction in the need for revascularization after treatment with drug-eluting stents as compared with bare metal stents.6 The issue of revascularization in diabetic patients with multivessel CAD will be reexamined using sirolimus-eluting stents in the Future REvascular-

ization Evaluation in patients with Diabetes mellitus; Optimal Management of multivessel disease (FREEDOM) trial8; however, even if restenosis is abolished, the differential clinical impact of disease progression between diabetic patients treated with CABG surgery and those treated with PCI will persist.

Is our approach fundamentally flawed? Although both angioplasty and bypass surgery are effective means of revascularization, neither has been shown to reduce the incidence of myocardial infarction (MI) in stable angina, and only CABG surgery has been shown to be effective in improving survival (in limited subsets of patients with left main coronary artery disease and triple vessel or proximal left anterior descending artery disease with impaired left ventricular function).9 In contrast, studies on cholesterol lowering show marked reductions in coronary heart disease events both in primary10 and secondary11 prevention. For example, in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS),10 lovastatin treatment was associated with a 37% overall risk reduction (43% in diabetic patients), and in the Scandinavian Simvastatin Survival Study (4S),11 simvastatin therapy was associated with a 32% overall risk reduction (55% in diabetic patients). Because of intravascular ultrasonography, we now know that atherosclerosis is a diffuse systemic disease that is not limited to the stenoses identified on angiography. We also know that most acute coronary syndromes and acute MIs are caused by ruptures of previously nonobstructive plaques. Although neither angioplasty nor CABG surgery directly addresses the latter issue, bypass surgery has a natural advantage because it provides additional conduits to the distal circulation operating in parallel to the native artery. These conduits can limit the size of subsequent infarcts and decrease the likelihood of death. This is not true for angioplasty, in which the arterial tree remains a serial circuit dependent on antegrade flow.

Conclusion In patients with diabetes who have multivessel disease, in particular, we may provide better and more cost-effective care by either referring them for CABG surgery or by using drug-eluting stents to treat angina-producing lesions only and concentrating on effective risk-factor modification.