D. Impact of Diabetes in ACS Adverse implications of diabetes in patients with ACS Content Points: Diabetes is an important comorbid factor in UA/NSTEMI. It is estimated that 20% to 25% of patients who present with UA/NSTEMI have diabetes.1 Diabetes is associated with a higher prevalence of triple-vessel disease. In the NHLBI PTCA2 registry of patients undergoing a first balloon angioplasty between 1985 and 1986, those with diabetes had a 27.7% prevalence of triple-vessel disease compared with a 17.7% prevalence in nondiabetics. Patients with diabetes have more advanced (greater number of complex lesions) and more diffuse disease (atherosclerotic disease involving a larger proportion of the coronary tree) than nondiabetics.2,3 1 Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guideline (Committee on the Management of Patients with Unstable Angina). Available at: http://www.acc.org/clinical/guidelines/unstable/unstable.pdf. 2 Kip KE, Faxon DP, Detre KE, Yeh W, Kelsey SF, Currier JW. Coronary angioplasty in diabetic patients. The National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Circulation. 1996;94: 1818-1825. 3 Laskey WK, Selzer F, Vlachos HA, Johnston J, Jacobs A, King SB III, et al. Comparison of in-hospital and one-year outcomes in patients with and without diabetes mellitus undergoing percutaneous catheter intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry). Am J Cardiol. 2002;90:1062-1067.

Adverse impact of diabetes on survival following PCI Content Points: Data on PCI procedures collected from the NHLBI Dynamic Registry between 1997 and 1999 show that diabetes is associated with higher mortality over the 12 months following the procedure.1 As shown, the 1-year mortality rate following PCI among 1058 patients with diabetes was 8.96%. The corresponding mortality among 3571 patients without diabetes was 4.18% (P = 0.0001). 1 Laskey WK, Selzer F, Vlachos HA, Johnston J, Jacobs A, King SB III, et al. Comparison of in-hospital and one-year outcomes in patients with and without diabetes mellitus undergoing percutaneous catheter intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry). Am J Cardiol. 2002;90:1062-1067.

ARTS: CABG vs stenting in patients with and without diabetes Content Points: Trials of coronary revascularization strategies in patients with diabetes indicate that outcome is better following CABG surgery than with PTCA.1,2 The Arterial Revascularization Therapy Study (ARTS) was a multicenter evaluation of stenting versus CABG in 1205 patients with stable, multivessel CAD.3 Stents were implanted according to current clinical practice. Since no US centers were involved in the ARTS trial, GP IIb/IIIa inhibitor use was low: 18/600 (3%) patients.3 Both diabetic and nondiabetic cohorts showed no significant difference between CABG and stenting with regard to death, cerebrovascular events, and MI (data not shown).4 The slide summarizes the rate of target vessel revascularization (combined CABG and PTCA) at 1 year.4 In both cohorts, stenting was associated with a significantly higher rate of this outcome compared with CABG (P < 0.001 for all comparisons). - However, the rate of target vessel revascularization in stented diabetics was significantly greater than in stented nondiabetics (22.3% vs 15.6%; P = 0.04) As suggested by the next slide, more effective antithrombotic therapy may reduce the gap between CABG and PCI in diabetics. 1 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;96:1761-1769. 2 King SB III, Kosinski AS, Guyton RA, Lembo NJ, Weintraub WS. Eight-year mortality in the Emory Angioplasty versus Surgery Trial (EAST). J Am Coll Cardiol. 2000;35:1116-1121. 3 Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJRM, Schönberger JPAM, et al. Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease. N Engl J Med. 2001;344:1117-1124. 4 Abizaid A, Costa MA, Centemero M, Abizaid AS, Legrand VMG, Limet RV, et al. Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients. Insights from the Arterial Revascularization Therapy Study (ARTS) trial. Circulation. 2001;104:533-538.

EPISTENT: GP IIb/IIIa inhibition reduces target vessel revascularization in diabetics undergoing stenting Content Points: Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial randomized 2399 patients scheduled for elective or urgent revascularization to stenting plus placebo, stenting plus abciximab (0.25-mg/kg bolus followed by 0.125 mg/kg/min for 12 h), or balloon angioplasty plus abciximab.1 The slide summarizes the rate of target vessel revascularization in three revascularization strategies according to the presence or absence of diabetes. In stented patients with diabetes, abciximab had a substantial effect on reducing this outcome. The rate of revascularization was 13.7% for stent plus abciximab versus 22.4% stent plus placebo (P = 0.035). - The rate in diabetic patients assigned to stent plus abciximab was similar to that of nondiabetics assigned to the same strategy (13.7% vs 15.6%) These data demonstrate that antithrombotic therapy (abciximab) lowers the risk of repeat revascularization in diabetic patients undergoing stenting. Use of a coated stent (described earlier in this section) may further benefit this high-risk population. 1 Topol EJ, Mark DB, Lincoff AM, Cohen E, Burton J, Kleiman N, et al, for the EPISTENT Investigators. Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: Results from a multicentre randomised trial. Lancet. 1999;354:2019-2024.

1 in 3 NSTEMI patients: Culprit lesion not identified on angiography Content Points: VANQWISH1 compared clinical outcomes in 462 patients with NSTEMI randomly assigned to early-invasive strategy with 458 patients who received early conservative treatment. Kerensky et al retrospectively analyzed the coronary angiograms of 350 patients randomized to the early-invasive strategy.2 The culprit lesion was identified in 63% of cases. - That is, in ~1 in 3 patients the culprit lesion could not be identified angiographically Multiple culprit lesions were identified in 14% of patients. These findings are consistent with the diffuse nature of coronary atherosclerotic disease and particularly relevant to diabetics since, as discussed in an earlier slide, these patients have a greater predisposition to have more diffuse disease than nondiabetics. These findings also support the need for aggressive lipid lowering as an adjunct to PCI, to stabilize lesions throughout the coronary vasculature. In many cases, however, CABG will be an option because, per se, it addresses a longer arterial segment than the site-specific PCI procedure. 1 Boden WE, O'Rourke RA, Crawford MH, Blaustein AS, Deedwania PC, Zoble RG, et al, for the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. N Engl J Med. 1998;338:1785-1792. 2 Kerensky RA, Wade M, Deedwania P, Boden WE, Pepine CJ, for the Veterans Affairs Non-Q-Wave Infarction Strategies in-Hospital (VANQWISH) Trial Investigators. Revisiting the culprit lesion in non-Q-wave myocardial infarction: Results from the VANQWISH trial angiographic core laboratory. J Am Coll Cardiol. 2002;39:1456-1463.

ACC/AHA guidelines for UA/NSTEMI: Revascularization in patients with diabetes Content Points: The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines for management of patients with non-ST-elevation ACS1 state that for patients with multivessel disease, CABG with use of the internal mammary arteries is preferred over PCI in patients being treated for diabetes. This is a class I recommendation (level of evidence: B). PCI for diabetic patients with single-vessel disease is a class IIa recommendation (level of evidence: B). When a stent is implanted, abciximab should be used as adjunctive antithrombotic therapy. This is also a class IIa recommendation (level of evidence: B). Under the ACC/AHA classification, class I refers to conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective. Class IIa refers to conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment, but for which the weight of evidence/opinion is in favor of usefulness/efficacy. Level of evidence B refers to data derived from small randomized trials or nonrandomized trials such as observational registries. 1 Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guideline (Committee on the Management of Patients with Unstable Angina). Available at: http://www.acc.org/clinical/guidelines/unstable/unstable.pdf.

ACC/AHA guidelines for UA/NSTEMI: Class I recommendations for antithrombotic therapy Content Points: For both diabetic and nondiabetic patients with ACS, antithrombotic agents have an important role. As shown on the slide, ACC/AHA class I recommendations for antithrombotic therapy tailor the intensity of treatment to individual risk.1 An LMWH can be substituted for UFH in patients for whom ACS is likely or definite. However, the present recommendations reserve UFH for patients undergoing intervention, although it is noted that data suggest that enoxaparin may provide more reproducible inhibition of platelet aggregation and less prolongation in bleeding time. Because of the number of studies that have appeared supporting the use of enoxaparin, the following class IIa recommendation is given: - Enoxaparin is preferable to UFH unless CABG is planned within 24 hours, since the anticoagulant effect of UFH can be reversed more readily More recent data (discussed in this slide program) provide further insight into the role of LMWH in patients for whom PCI is planned. Under the ACC/AHA classification, class I refers to conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective. Class IIa refers to conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment, but for which the weight of evidence/opinion is in favor of usefulness/efficacy. 1 Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guideline (Committee on the Management of Patients with Unstable Angina). Available at: http://www.acc.org/clinical/guidelines/unstable/unstable.pdf.