(Circulation. 1996;94:1804-1806.)
© 1996 American Heart Association, Inc.
Articles |
The Interventional Cardiologist and the Diabetic Patient
Have We Pushed the Envelope Too Far or Not Far Enough?
Jefferson Medical College, Philadelphia, Pa.
Correspondence to Sheldon Goldberg, MD, Division of Cardiology, Jefferson Medical College, 1025 Walnut St, Suite 410, Philadelphia, PA 19107.
Key Words: Editorials • diabetes • angioplasty
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Introduction |
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 Top Introduction Why Are Diabetics at...Clinical Implications and Future...References |
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One of the greatest challenges faced by the interventional cardiologist is the mature application of clinical judgment in the optimal selection of patients for transcatheter intervention, surgical revascularization, or medical therapy. This challenge is particularly formidable in diabetic patients with obstructive coronary disease because of the difficult anatomic and biological substrate present in these patients. In this issue of Circulation, Kip et al1 report the results of a comparison of outcomes after first-time percutaneous transluminal coronary angioplasty (PTCA) in diabetic versus nondiabetic patients for up to 9 years after entry into the NHLBI 1985-1986 PTCA Registry. This careful analysis involving a total of 2114 patients enrolled at 16 clinical sites, 281 (13%) of whom were diabetic, showed increased short- and long-term risk when balloon angioplasty was used to revascularize the ischemic myocardium in diabetic patients. An examination of the baseline clinical characteristics showed that diabetics were older and sicker than the other patients in the registry and had more frequent comorbid conditions, such as hypertension and congestive heart failure. With regard to angiographic characteristics, despite similar preserved left ventricular function (ejection fraction of 59%), diabetic patients had a greater incidence of triple-vessel disease (28% versus 18%) and more diffuse disease in both proximal and distal coronary artery segments. Despite the similarity in the number of lesions attempted, diabetic patients had a significantly higher risk of in-hospital death, nonfatal infarction, and a combined end point of death/myocardial infarction/emergency surgery. Of note, the procedural success rate was similarly low in the diabetic and nondiabetic patients; total procedural success, defined as success in all attempted lesions, was only 71% and 76%, respectively. A particularly disturbing statistic was the excess of in-hospital mortality in the female diabetics—a striking 8.3%—while the estimated risk of in-hospital mortality was nearly tripled for all diabetic patients. Analysis of the long-term 9-year follow-up data was equally sobering: mortality was doubled in the diabetics (36% versus 18%), with a higher rate of later myocardial infarction between years 2 and 7. The rates of coronary bypass graft surgery as well as repeat balloon angioplasty showed increasing diversion with time for the two groups, with a 1.34 relative risk (P<.01) present in diabetic patients.
Another disturbing report regarding PTCA in diabetics was the NHLBI clinical alert issued on September 21, 1995, regarding the findings of the Bypass Angioplasty Revascularization Investigation.2 3 In that multicenter trial, patients with significant obstruction in at least two of the coronary vessels supplying two or three major territories and who had severe clinical ischemia were randomly assigned to either coronary bypass graft surgery or balloon angioplasty as an initial revascularization strategy. Between 1988 and 1991, 1829 patients, including 353 medication-requiring diabetics (19%), were randomized at 18 clinical sites. At an urgent session of the data safety and monitoring committee held on September 13, 1995, a review of the 5-year mortality rates showed poor long-term results in both groups, with a near doubling of mortality in diabetic patients assigned to PTCA (35% versus 19%; P=.02). In contrast, the 5-year death rates were similar at 9% in nondiabetic patients treated with either revascularization strategy.
Other reports4 have shown high initial angioplasty success for diabetics versus nondiabetic patients but an excess of death, myocardial infarction, coronary artery bypass graft surgery, and repeat PTCA over longer-term follow-up, especially in insulin-requiring patients. In the Emory Angioplasty Surgery Trial, there was no excess mortality noted in diabetics randomized to PTCA versus bypass surgery, but the number of patients was relatively small.5
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Why Are Diabetics at Increased Risk? |
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TopIntroductionWhy Are Diabetics at...Clinical Implications and Future...References |
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The mechanisms for the increased risk of diabetic patients treated with oral agents or insulin who undergo mechanical revascularization are multifactorial and involve vascular, hematologic, and metabolic factors acting in concert.6 Thus, diabetic patients have a higher incidence of fissured plaques, with increased vulnerability for abrupt closure and resultant acute myocardial infarction.7 Furthermore, diabetic patients have increased blood viscosity,8 enhanced platelet aggregation,9 10 and increased synthesis of thromboxane A2,11 which factors further increase the propensity for platelet aggregation and coronary spasm. In addition, fibrinogen levels are relatively elevated in diabetics along with factor VIII and fibrinopeptide A levels.9 Endothelial dysfunction may be more pronounced in diabetics, and endogenous fibrinolysis is impaired.12
Given the prothrombotic milieu present in diabetic coronary vessels and the fact that standard balloon angioplasty involves some degree of plaque fracture and dissection as part of the mechanism of acute lumen enlargement, it is hardly surprising that diabetic patients may experience a higher rate of periprocedural infarction and death. The worse long-term fate of diabetics is understandable given the more extensive degree of atherosclerotic involvement and a possible accelerated rate of intimal hyperplasia in response to either balloon angioplasty or existing metabolic derangements. Finally, it is likely that acute ischemic complications during angioplasty are more poorly tolerated in diabetic patients. For example, diabetics suffering acute myocardial infarction have a significantly higher mortality rate than nondiabetics.13 14 In addition, diabetic women appear particularly vulnerable to congestive heart failure and death after acute myocardial infarction. Thus, diabetics undergoing PTCA may not only be more prone to develop complications but may also suffer more severe sequelae as a consequence.
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Clinical Implications and Future Directions |
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TopIntroductionWhy Are Diabetics at...Clinical Implications and Future...References |
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The current reports indicate that diabetic patients fare relatively poorly when subjected to balloon angioplasty compared with nondiabetic patients. Although there appears to be an advantage to surgical revascularization compared with standard PTCA in a certain subgroup, ie, those undergoing a first-time procedure for multivessel disease, the results for both balloon angioplasty and bypass surgery are far from satisfactory. Given these facts, the clinician must ask "Have we pushed the envelope too far?" regarding transcatheter revascularization in this high-risk group of patients. A realistic ray of hope is provided by the accumulating data showing that we have entered a new era in interventional cardiology owing to the superior results achieved with the newer mechanical and pharmacological interventions. Thus, coronary stents have proved effective in conferring a superior angiographic and clinical outcome both in the short term and with respect to long-term patency.15 16 These devices have proved their efficacy for both threatened and abrupt closure as well as restenosis reduction (relative reduction of
33% compared with balloon angioplasty) as a result of sealing of intimal flaps and have resulted in a reduction in both early elastic recoil and chronic vascular remodeling. It should be noted that current-generation devices have been tested mainly in larger coronary arteries for discrete lesions. The development of specific stents designed for smaller vessels and for use in cases of more diffuse disease in conjunction with coatings17 to prevent thrombosis and intimal hyperplasia may improve clinical results in diabetic coronary vessels. The current use of the powerful platelet glycoprotein IIb/IIIa receptor antagonists to make the arterial wall passive and reduce acute closure, myocardial infarction, and clinical restenosis in conjunction with PTCA represents a major advance that was unavailable to the 1985 to 1986 NHLBI investigators. The potential for benefit of these compounds in diabetic patients would seem particularly strong given the dramatic reduction in cardiac events noted in high-risk patients undergoing PTCA. Major cardiac events were reduced by 35% at 30 days, whereas clinical restenosis was reduced by 26% at 6 months when the monoclonal antibody c7E3 was given in conjunction with PTCA in patients with unstable ischemic syndrome and/or high-risk lesion morphology.18 19 Furthermore, the development of oral glycoprotein IIb/IIIa receptor antagonists may impact favorably on long-term results. Additional well-designed trials designed to test the efficacy of these new approaches in diabetic patients are clearly warranted. Other new avenues that may lead to more successful revascularization outcomes include the use of minimally invasive surgery20 in conjunction with transcatheter intervention in the same patient. For example, a patient with a diffusely diseased left anterior descending artery and a discrete stenosis in a large, mid, right coronary artery with diffuse distal disease might be approached by the use of minimally invasive left internal mammary artery graft and a subsequent stent of the right coronary artery. This multidisciplinary approach involving clinical cardiologists, interventionists, and coronary surgeons will also require testing in clinical trials.
In the meantime, the clinician faced with the diabetic patient with significant obstructive coronary disease should give special thought to whether any mechanical revascularization is really desirable and necessary and, if it is, involve a revascularization team of clinicians with experience in transluminal and bypass methods to attempt to choose the most reasonable options for each clinical and specific anatomic scenario. The results of new studies that push the envelope still further will help guide our future therapeutic strategies.
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Acknowledgments |
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We wish to thank Denise Gidaro for her assistance in the preparation of this manuscript.
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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References |
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