Improved Outcomes with Stenting in Diabetics: Controlling the Unruly Platelet
Improved Outcomes with Stenting in Diabetics: Controlling the Unruly Platelet
abstract & commentary
Synopsis: A strategy of stent-abciximab was more effective in reducing the need for future revascularization in diabetic patients than stent-placebo or POBA-abciximab.
Source: Marso SP, et al. Circulation 1999;100: 2477-2484.
It is well accepted that diabetics have less optimal angiographic and clinical outcomes following percutaneous intervention (PCI) than nondiabetics, particularly in individuals with multivessel disease. The first clue to an adverse outcome following PCI in diabetics came from the Bypass Angioplasty Revascularization Investigation (BARI) trial, which demonstrated improved survival rates in diabetics undergoing bypass surgery vs. plain old balloon angioplasty (POBA) (Circulation 1997;96:1761-1769); other studies, but not all, have supported these observations. The use of stenting in the diabetic has resulted in conflicting results as to whether outcomes are improved over POBA. While platelet IIb/IIIa receptor inhibition has not been shown to improve outcomes in diabetics treated with POBA, the question of stent placement in conjunction with platelet inhibition has not been addressed. The EPISTENT trial analyzed a subset of 491 diabetic patients who were prospectively randomized into three groups: stent-placebo, stent-abciximab, and POBA-abciximab. Most patients had stable single-vessel disease. Approximately 20% of the overall EPISTENT cohort were diabetic, with a mean age of 60 years. The diabetic patients had a greater incidence of markers of insulin resistance, including obesity and hypertension. Approximately half of the patients had a prior myocardial infarction (MI), and one out of six had a recent MI (within 7 days of PCI). The primary end point for this substudy was a composite of all-cause mortality, nonfatal MI, or target-vessel revascularization (TVR) at six months. Patients were followed up to one year. An angiographic substudy involving 900 patients, of whom 132 were diabetic, was also analyzed.
The results clearly indicated that stent-abciximab therapy in the diabetic was substantially better than stent-placebo or POBA-abciximab. The composite endpoint, death, and MI rates were reduced by 50%. There was a greater than 50% reduction in six-month TVR rates; the stent-abciximab patients had a similar sixmonth TVR rate as nondiabetics treated with stent-abciximab, whereas stenting without platelet blockade was associated with increased TVR rates in diabetics compared to nondiabetics. There was an absolute decrease in events, and consistent benefit for all endpoints in the stent-abciximab group compared to stent-placebo. One-year survival was better in these individuals (4.1% vs 1.2%; P = 0.11). Because of some discrepancies in baseline characteristics, a multivariate analysis was carried out, which confirmed the overall group observations. Stenting-abciximab in diabetics was associated with a 50% reduction in the primary end point. The results were similar when only diabetics treated with medication were analyzed. Of interest, in the entire diabetic cohort, including drug-treated diabetics, there was a reduction in six-month TVR rates for stent-abciximab patients vs. stent-placebo (9.2% vs 18.2%; P = 0.05), with a strong trend for increased survival in the stent-placebo group at one year.
The relatively small number of individuals in the angiographic cohort confirmed the larger study results, indicating an improvement in net luminal gain at six months for stent-abciximab compared to stent-placebo (0.88 vs 0.55 mm; P = 0.01). Late loss index was less for abciximab patients, and the restenosis rate at six months was almost half that in the stent-placebo group. Restenosis rates for POBA-abciximab were 20%, compared to 7.8% and 14.2% for stent-abciximab and stent-placebo groups, respectively. Diabetics with markers of insulin resistance (hypertension and obesity) had an improvement in clinical outcomes with stenting and IIb/IIIa platelet inhibition. These clinical markers of insulin resistance were significant predictors of increased TVR rates in multivariate analysis; procedural outcomes were improved with stent-abciximab, and contributed greatly to the favorable six-month outcomes in this group. These patients had a decreased six-month rate of death, MI, and need for repeat revascularization. Marso and colleagues conclude that a treatment strategy with stent-abciximab "both improved safety profile for stenting and decreased the need for future revascularization procedures in diabetic patients." They provide a detailed discussion of potential mechanisms and suggest that enhanced platelet activation in the diabetic is an important adverse factor, and that IIb/IIIa platelet receptor inhibition decreases restenosis in diabetics who receive a stent. This may be due to a less intimal neoproliferation and mural thrombis following balloon or stent coronary arterial injury. Abciximab binds not only to the platelet IIb/IIIa receptor but also to the vitronectin receptor on endothelial and smooth muscle cells, which may also be important in decreasing restenosis and intimal proliferation. In EPISTENT, abciximab was not effective in reducing restenosis after POBA.
Comment by Jonathan Abrams, MD
The conundrum of the diabetic with obstructive coronary disease has been the focus of increasing attention over the past several years. Many individuals, including William O’Neil and the BARI investigators, have suggested that bypass surgery is the preferred revascularization strategy for the diabetic with multivessel disease. Results of EPISTENT indicate that diabetics who receive a stent fare better than those who have POBA, but all reported studies have not reached the same conclusion. The advent of IIb/IIIa platelet receptor inhibitors has provided evidence that short- and long-term outcomes are improved in individuals who receive a PCI, particularly when they have high-risk features. This study strongly suggests that abciximab also may play an important role in decreasing morbidity and mortality in diabetic patients undergoing angioplasty with stenting. The data from the EPISTENT trial suggest that the use of abciximab and a stent moves the diabetic undergoing PCI closer to the nondiabetic with respect to morbidity and mortality, although not completely so. This is similar to recent hypertension and statin trials, which are concordant with a major risk reduction in the diabetic with effective therapies that favorably alter clinical outcomes and eliminate much of, but not all, the risk associated with diabetes. This single study should not completely change our therapy, but the results of this trial are not surprising and are concordant regarding all end points. Thus, the interventionalist treating the diabetic should strongly consider the use of stenting as well as a platelet IIb/IIIa inhibitor. Given the present state of knowledge, it does not seem presumptuous to use such an approach until more data are available. The provocative suggestion that insulin resistant features contribute to less favorable PCI outcomes suggests that such patients may also benefit from the same approach. This clearly requires confirmation in future studies.
Diabetics undergoing percutaneous coronary interventions show the lowest total mortality, MI, and target vessel revascularization with:
a. balloon angioplasty.
b. balloon angioplasty plus abciximab.
d. stent plus abciximab.
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