Restenosis Rates in Diabetic Patients
A Comparison of Coronary Stenting and Balloon Angioplasty in Native Coronary Vessels
Background Diabetes is a major risk factor for restenosis after coronary balloon angioplasty. Recent studies have shown that coronary stenting significantly reduces restenosis compared with balloon angioplasty alone. However, limited information is available on the effect of coronary stenting in diabetic patients.
Methods and Results We designed this study to analyze the effect of diabetes on restenosis in patients treated with either balloon angioplasty or coronary stenting who were enrolled in a 6-month angiographic follow-up program. Three hundred consecutive patients, 19% of whom were diabetics, who underwent coronary stent implantation during a single-vessel procedure on native coronary vessels and who had 6-month angiographic follow-up constituted the study group (stent group). Three hundred consecutive patients who underwent 6-month angiographic follow-up after single-vessel conventional balloon angioplasty served as control patients (balloon group). Preprocedural, postprocedural, and follow-up angiograms were analyzed with quantitative angiography. In the balloon group, the restenosis rate was almost twofold higher in diabetic than in nondiabetic patients (63% versus 36%; P=.0002) owing to both a greater late loss (0.79±0.70 versus 0.41±0.61 mm, respectively; P<.0001) and a higher rate of late vessel occlusion (14% versus 3%, respectively; P<.001). In the stent group, restenosis rates were similar in diabetics and nondiabetics (25% versus 27%, respectively). Furthermore, in the stent group, late loss (0.77±0.65 versus 0.79±0.57 mm, respectively) and the rate of late vessel occlusion (2% versus 1%, respectively) did not differ significantly between diabetic and nondiabetic patients.
Conclusions Although diabetics have increased rates of restenosis and late vessel occlusion after simple balloon angioplasty, they have the same improved outcome with coronary stenting that has been documented in nondiabetic patients.
Coronary artery disease is frequently encountered in diabetic patients.1 2 Revascularization may be accomplished in such patients either by CABG or by PTCA. Recently, a report from the BARI study comparing CABG and PTCA in patients with multivessel disease showed that the mortality rate of diabetic patients treated by PTCA was almost two times higher than that of patients randomized to CABG. In contrast, the mortality rate of nondiabetic patients was similar whether they were treated by PTCA or CABG.3 Furthermore, it has been shown that diabetic patients have a higher rate of post-PTCA restenosis4 5 6 7 8 ; this has been suggested to reflect a higher propensity to develop neointimal hyperplasia.9
Intracoronary stent implantation has been shown to significantly reduce angiographic restenosis in humans10 11 ; the better long-term angiographic result is due to a better acute result and to the prevention of chronic remodeling despite an increase in neointimal hyperplasia.12 It is unclear if these favorable results may be extended to diabetic patients.
We therefore designed the present study to analyze the effect of coronary stenting in diabetic patients. Angiographic restenosis rates were compared between diabetic and nondiabetic patients undergoing coronary stenting or conventional balloon angioplasty.
From the records of our catheterization laboratory, we identified 300 consecutive patients who underwent 6-month angiographic follow-up after successful stent implantation during a single-vessel PTCA procedure on a native coronary vessel performed between April 1994 and March 1996 (stent group). As routinely performed in our institution,13 14 15 these patients were enrolled in a 6-month angiographic follow-up program: all patients were asked at the time of the initial procedure to return for a 6-month follow-up angiogram regardless of symptomatic status; an angiography could be performed earlier if there was clinical indication. During the above study period, the rate of 6-month angiographic follow-up was 83%; this rate was similar in diabetic (83%) and nondiabetic patients (82%).
Three hundred consecutive patients with 6-month angiographic follow-up after successful single-vessel conventional balloon angioplasty between March 1993 and April 1995 served as control patients (balloon group). As described above, during this period an angiographic follow-up was proposed to all patients at the time of balloon angioplasty. Angiographic follow-up was actually obtained in 82% of the patients, and the rate of follow-up was similar in diabetic (82%) and nondiabetic patients (81%). Patients in the latter group were included in an ongoing prospective study of genetic risk factors for restenosis. Angiographic and clinical data concerning some of the control patients have been reported previously.16 17
Diabetes Mellitus and Treatment: Definitions
At the time of the initial procedure, patients were classified as diabetic if they were treated by oral hypoglycemic drugs or insulin or if they had a previous history, documented on their medical chart, of elevated (≥140 mg/dL) fasting blood glucose on at least two separate occasions in conjunction with adhering to ongoing dietary measures to control their glucose level.
Diabetic patients were classified in three categories depending on antidiabetic management at the time of the initial procedure: (1) diet alone, (2) oral hypoglycemic drugs (diet and oral hypoglycemic drugs but no insulin), and (3) insulin (irrespective of other therapy).
Balloon angioplasty and coronary stenting were performed according to the standard technique in our laboratory.18 All patients received aspirin 300 mg/d; a bolus dose of heparin (10 000 IU) was administered just before PTCA. In patients who underwent coronary stenting, treatment with ticlopidine (500 mg) was started immediately after the procedure. In both groups of patients, when the procedure was performed in the morning, no heparin was administered after the procedure, and the introducer sheath was removed when the effects of heparin had worn off. When the procedure was performed in the afternoon, 1000 IU/h heparin was infused until 6 am the next day, and the sheath was removed later that morning.18 The procedure was considered successful when the residual luminal narrowing in the dilated segment immediately after angioplasty was <50% and when no major complication (ECG or enzymatic evidence of myocardial infarction, the need for bypass surgery during hospitalization, or in-hospital death) occurred. In terms of antithrombotic treatment at discharge, the patients who underwent conventional balloon angioplasty received aspirin alone, whereas the patients who had coronary stent implantation received a combination of aspirin (325 mg) and ticlopidine (500 mg) daily for 6 weeks and then aspirin alone.
Qualitative Angiographic Analyses
The qualitative analyses were performed independently by two experienced interventional cardiologists. Disagreements were resolved by a further joint reading.
The anterograde blood flow was graded using the classification of the TIMI study group.19
The reasons for stent placement were classified in three categories: (1) bailout implantation (for acute or threatened acute occlusion during or after the procedure), (2) implantation for a suboptimal result, or (3) elective implantation. Acute closure was defined as vessel occlusion with TIMI grade 1 or 0 flow, based on the appearance of the vessel immediately before stent insertion. Threatened closure was defined as the presence of a significant dissection immediately after angioplasty (more severe than grade B according to the American Heart Association/American College of Cardiology classification20 ) associated with a reduction in flow in the vessel or with ECG evidence of myocardial ischemia. A suboptimal result was defined as the presence of a visually estimated residual stenosis >40% after dilatation with or without an associated nonocclusive dissection (grade A or B) but with normal blood flow (TIMI grade 3). Implantation was classified as elective when it had been decided before the procedure.
Quantitative Coronary Angiography
Quantitative computer-assisted angiographic measurements were performed on end-diastolic frames with use of the CAESAR (Computer-Assisted Evaluation of Stenosis and Restenosis) system. A detailed description of this system has been reported previously.21 We routinely perform angiography in at least two projections after the intracoronary injection of isosorbide dinitrate (2 mg). These projections are recorded in our database, and after injection of isosorbide dinitrate, the follow-up angiogram is performed in the same projections. The following definitions were used: the acute gain associated with the procedure was defined as the difference between the MLD immediately after stent implantation and the MLD before the procedure; the late loss during the follow-up period was defined as the difference between the MLD immediately after stent implantation and the MLD at follow-up; the net gain was defined as the difference between the acute gain and the late loss; and finally, to define restenosis, we used a categorical approach with the classic criterion of >50% stenosis at follow-up.
Data are presented as mean±SD. For continuous variables, comparisons between two groups were made with the Student t test, whereas comparisons between more than two groups were made with ANOVA followed by Scheffé’s F test. Differences between proportions were assessed by χ2 analysis. A value of P<.05 was considered to indicate statistical significance.
The baseline characteristics of the study population are shown in Table 1⇓. Most of the 600 patients were male (84%), with a mean age of 59±11 years. Thirty-three percent of the patients had unstable angina, and 33% had experienced a recent (<1 month previous) myocardial infarction. The incidence of diabetes was the same in the balloon group (19%) and the stent group (19%). There were no statistically significant differences in baseline characteristics between diabetic and nondiabetic patients in either group except for hypertension, which was more frequent in diabetic patients (P<.01). In the stent group, stenting was attempted for bailout in 13%, for a suboptimal result after conventional balloon angioplasty in 69%, and electively in 18% of the patients. Most of the patients underwent implantation of a Palmaz-Schatz stent (66%). In 81%, a single stent was used.
Angiographic Outcome in the Balloon Angioplasty Group
The results of quantitative angiography in the balloon group are shown in Table 2⇓, and cumulative curves are illustrated in the top panel of the Figure⇓. There were no significant differences in reference diameter between diabetic and nondiabetic patients at any of the three time points studied (before the procedure, after the procedure, and at 6-month follow-up). The MLD before and after the procedure did not differ significantly between the two groups. At follow-up angiography, the MLD was significantly (P<.0001) smaller and the percent diameter stenosis was significantly (P<.0001) greater in diabetic patients than in nondiabetic patients. The late loss during the follow-up period was almost twofold greater (P<.0001) in diabetic patients (0.79±0.70 mm) than in nondiabetic patients (0.41±0.61 mm). The net gain was significantly (P<.0001) higher in nondiabetic patients (0.75±0.67 mm) than in diabetic patients (0.36±0.74 mm). As analyzed by the categorical approach using the >50% diameter stenosis criterion, 63% of diabetic patients had restenosis compared with 36% of nondiabetic patients (P=.0002).
In the balloon group, total occlusion of the dilated site at follow-up occurred in 3% of nondiabetic patients but in 14% of diabetic patients (P=.001; Table 2⇑). When patients with total occlusion at follow-up were excluded from the analysis, late loss was still significantly higher and MLD at follow-up significantly smaller in diabetic than in nondiabetic patients (late loss: 0.63±0.60 versus 0.37±0.54 mm, P=.003; MLD at follow-up: 1.37±0.65 versus 1.63±0.59 mm, P=.006).
In diabetic patients, a trend toward a worse angiographic outcome was observed in patients treated with insulin (80% restenosis rate) that did not reach statistical significance (Table 4⇓).
Angiographic Outcome in the Coronary Stent Group
The results of quantitative angiography in the stent group are shown in Table 3⇓, and cumulative curves are presented in the bottom panel of the Figure⇑. As in the balloon group, there were no significant differences in reference diameter or stenosis severity before and after the procedure between diabetic and nondiabetic patients. At follow-up angiography, stenosis severity (MLD, percent diameter stenosis) was similar in both groups. The late loss and the net gain were also similar in both groups (diabetic patients: late loss=0.77±0.65 mm, net gain=1.00±0.70 mm; nondiabetic patients: late loss=0.79±0.57 mm, net gain=0.98±0.72 mm). Twenty-five percent of diabetic patients had restenosis (>50% diameter stenosis at follow-up) versus 27% of nondiabetic patients (P=NS).
In the stent group, total occlusion of the dilated site at follow-up occurred in 1% of nondiabetic and 2% of diabetic patients (P=NS; Table 3⇑). Because the overall frequency of total occlusion at follow-up was low in the stent group, the results were not modified when those patients were excluded from the analysis (data not shown).
Within the group of diabetic patients, the angiographic outcome was similar in the three subgroups (Table 4⇓).
The present study demonstrates that despite similar baseline characteristics, diabetic patients who underwent balloon angioplasty had a much higher risk of restenosis than nondiabetic patients also treated by balloon angioplasty. The immediate result of angioplasty (acute gain) was not affected by diabetes; the increased risk of restenosis was related both to a greater degree of late luminal loss during the follow-up period and to the more frequent occurrence of total vessel occlusion. By contrast, in the group of patients undergoing coronary stenting, the presence of diabetes was not associated with a greater risk of restenosis, as demonstrated by the quantitative angiographic results summarized in Table 3⇑. The 25% rate of restenosis after coronary stenting in diabetic patients compares favorably with the 63% rate observed in otherwise comparable patients after conventional balloon angioplasty. This demonstrates that coronary stenting is associated with a significant improvement in midterm angiographic follow-up in diabetic patients.
Diabetes Mellitus as a Risk Factor for Restenosis After Balloon Angioplasty
Previous studies have shown that diabetes is an independent risk factor for restenosis after balloon angioplasty, with reported restenosis rates ranging from 47% to 69%.4 5 6 7 8 Our study is consistent with these reports, showing an increased restenosis rate in diabetic patients treated with balloon angioplasty (63%). This prohibitive rate of restenosis may be one of the reasons for the poor clinical outcome recently reported in diabetic patients treated with balloon angioplasty.3 22
Diabetes Is Not a Risk Factor for Restenosis After Coronary Stenting
Two recent randomized trials have demonstrated that coronary stent implantation may decrease the risk of restenosis10 11 ; however, limited and conflicting results are available on the effect of diabetes on restenosis after coronary stenting.23 24 25 26 The results of the present study, demonstrating that the presence of diabetes is not associated with an increased risk of restenosis after coronary stenting, extend the results of previous reports in which diabetes was not found to be a risk factor for in-stent restenosis.23 26 These results are not in accordance with a report by Carroza et al24 that demonstrated an increased rate of restenosis in diabetic patients after stenting. This discrepancy may be related to the fact that in the study by Carroza et al,24 most of the diabetic patients underwent stent implantation at saphenous vein graft lesions, whereas the present study was restricted to procedures performed in native vessels.
Mechanisms of Restenosis in Diabetic Patients
The exact mechanisms responsible for the increased restenosis rate after conventional balloon angioplasty in diabetic patients are unknown. It has been suggested that the prothrombotic milieu present in diabetic coronary vessels, including increased blood viscosity, increased fibrinogen and factor VIII levels, a decrease in the biological activity of antithrombin III, and enhanced platelet aggregation, could play a role in this phenomenon.27 28 29 Previous studies demonstrating that thrombus is both more frequently associated with coronary lesions in diabetic patients30 and is a predictor of late vessel occlusion after angioplasty,15 as well as a study by Rensing et al4 showing that diabetes was a risk factor for late vessel occlusion, are consistent with this hypothesis. Our results demonstrating a fourfold increase in the occlusion rate at follow-up in diabetic patients lend further support to this hypothesis. The analysis of restenosis rates performed after exclusion of the patients with total occlusion at follow-up suggests, however, that late vessel occlusion is not the sole explanation for the increased restenosis rate in diabetic patients and that other mechanisms may be involved.
It has also been suggested that the degree of neointimal hyperplasia might be greater as a consequence of a stimulatory effect of growth factors such as insulin-like growth factor-1 on vascular smooth muscle cells.9 However, recent experimental31 32 33 and clinical34 studies have demonstrated that the contribution of neointimal hyperplasia to restenosis after balloon angioplasty is relatively limited and that lumen renarrowing is in fact mostly related to vessel remodeling (ie, chronic sclerosis with vessel constriction). Although further studies will be needed to directly address this question, a preliminary study by Murcia et al35 has shown that the specific feature of atherectomy specimens from restenotic lesions retrieved in diabetic patients was not an enhanced smooth muscle proliferation but rather a greater fibrotic response that may lead to vessel constriction.
The present results provide new insights into the mechanisms involved in restenosis in diabetic patients. Indeed, because the stent prevents the remodeling process, restenosis after coronary stenting is mainly the consequence of neointimal hyperplasia within the stent.12 Thus, factors that directly affect the degree of neointimal hyperplasia would be more likely to influence restenosis after coronary stenting than restenosis after balloon angioplasty. Our results showing that diabetes is a major risk factor for restenosis after balloon angioplasty but not after coronary stenting do not support the hypothesis that there is a greater degree of neointimal hyperplasia in diabetics but rather favor the hypothesis that diabetes may affect the remodeling process.
In addition, in the patients treated by stenting, diabetes was not associated with an increased risk of late vessel occlusion. Considering the high rate of late coronary occlusion in diabetic patients treated with balloon angioplasty, this suggests that in addition to its favorable effect on vascular remodeling, coronary stenting may also be effective in preventing late vessel occlusion. The potential mechanisms of the reduction in vessel reocclusion by coronary stenting are unclear. However, if we consider that the presence of a protruding thrombus as assessed by angioscopy at the balloon angioplasty site is a strong predictor of late vessel occlusion,15 it is likely that the mechanical effect of a coronary stent, by consolidation of the plaque and isolation of the lumen from all materials including thrombus present at the surface of the vessel, is the main reason for this favorable effect. The combination of two potent antiplatelet agents, aspirin and ticlopidine, systematically used after stent implantation in the present study is another possible explanation for this effect.18 36
Antidiabetic Regimen and Restenosis
To the best of our knowledge, no information is available on the importance of the type of diabetes as a risk factor for restenosis. The results of the present study suggest that patients requiring insulin therapy have the worst angiographic outcome after balloon angioplasty; however, due to the small size of the insulin group, these results need to be interpreted with caution. A larger prospective study is needed to address this issue.
Potential study limitations need to be addressed. First, this was not a randomized study. However, it was a relatively large series of consecutive patients with similar baseline characteristics enrolled prospectively in a 6-month angiographic follow-up program. Second, most of the patients in the stent group were not treated electively but rather because there was a suboptimal result after balloon angioplasty or as a bailout procedure. However, bailout coronary stenting has usually been associated with high restenosis rates,37 and one might expect an even better 6-month angiographic outcome if coronary stenting had been performed electively. Finally, this study focused on the 6-month angiographic follow-up and does not provide information on the clinical outcome.
Our study confirms that balloon angioplasty in diabetics is associated with a prohibitive rate of restenosis and that this technique of revascularization may not be the most appropriate technique to treat coronary artery disease in such patients. Diabetes, however, does not affect the restenosis rate when coronary stenting is performed. Furthermore, the lower restenosis rate in diabetic patients treated by stenting versus those treated by balloon angioplasty suggests that coronary stenting could significantly reduce restenosis in this subset of patients. This last issue will need to be validated by randomized trials focused on diabetic patients.
Selected Abbreviations and Acronyms
|CABG||=||coronary artery bypass grafting|
|MLD||=||minimal lumen diameter|
|PTCA||=||percutaneous transluminal coronary angioplasty|
|TIMI||=||Thrombolysis In Myocardial Infarction|
- Received January 20, 1997.
- Revision received March 17, 1997.
- Accepted April 13, 1997.
- Copyright © 1997 by American Heart Association
Frein FS, Scheuer J. Heart disease in diabetes. In: Rifkin H, Porte D Jr, eds. Ellenberg and Rifkin’s Diabetes Mellitus Theory and Practice. New York, NY: Elsevier Science Publishing Corp; 1990:812-823.
Alderman EL, Andrews K, Bost J, Bourassa M, Chaitman BR, Detre K, Faxon DP, Follman D, Frye RL, Hlatky M, Jones RH, Kelsey SF, Rogers WJ, Rosen AD, Hartzell S, Sellers MA, Sopko G, Sutton Tyrell K, Williams DO. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med. 1996;335:217-225.
Rensing BJ, Hermans WRM, Vos J, Tijssen JGP, Rutch W, Danchin N, Heyndrickx GR, Mast EG, Wijns W, Serruys PW, on behalf of the Coronary Artery Restenosis Prevention on Repeated Thromboxane Antagonism (CARPORT) Study Group. Luminal narrowing after percutaneous transluminal coronary angioplasty: a study of clinical, procedural, and lesional factors related to long-term angiographic outcome. Circulation. 1993;88:975-985.
Holmes DR Jr, Vlietstra RE, Smith HC, Vetrovec GW, Kent KM, Cowley MJ, Faxon DP, Gruentzig AR, Kelsey SF, Detre KM, Van Raden MJ, Mock MB. Restenosis after percutaneous transluminal coronary angioplasty (PTCA): a report from the PTCA Registry of the National Heart, Lung, and Blood Institute. Am J Cardiol. 1984;53:77C-81C.
Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R, Almond D, Teirstein PS, Fish RD, Colombo A, Brinker J, Moses J, Shaknovich A, Hirshfeld J, Bailey S, Ellis S, Rake R, Goldberg S. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med. 1994;331:496-501.
Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi J, Sigwart U, Colombo A, Goy JJ, Van Den Heuvel P, Delcan J, Morel M-A. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med. 1994;331:489-495.
Hoffmann R, Mintz GS, Dussaillant GR, Popma JJ, Pichard AD, Satler LL, Kent KM, Griffin J, Leon MB. Patterns and mechanisms of in-stent restenosis: a serial intravascular ultrasound study. Circulation. 1996;94:1247-1254.
Bauters C, McFadden EP, Lablanche JM, Quandalle P, Bertrand ME. Restenosis rate after multiple percutaneous transluminal coronary angioplasty procedures at the same site: a quantitative angiographic study in consecutive patients undergoing a third angioplasty for a second restenosis. Circulation. 1993;88:969-974.
Bauters C, Khanoyan P, McFadden EP, Quandalle P, Lablanche JM, Bertrand ME. Restenosis after delayed coronary angioplasty of the culprit vessel in patients with a recent myocardial infarction treated by thrombolysis. Circulation. 1995;91:1410-1418.
Bauters C, Lablanche JM, McFadden EP, Hamon M, Bertrand ME. Relation of coronary angioscopic findings at coronary angioplasty to angiographic restenosis. Circulation. 1995;92:2473-2479.
Hamon M, Bauters C, Amant C, McFadden EP, Helbecque N, Lablanche JM, Bertrand ME, Amouyel P. Relation between the deletion polymorphism of the angiotensin-converting enzyme gene and late luminal narrowing after coronary angioplasty. Circulation. 1995;92:296-299.
Lablanche JM, McFadden EP, Bonnet JL, Grollier G, Danchin N, Bedossa M, Leclercq C, Vahanian A, Bauters C, Van Belle E, Bertrand ME. Combined antiplatelet therapy with ticlopidine and aspirin: a simplified approach to intracoronary stent management. Eur Heart J. 1996;17:1373-1380.
Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB III, Loop FD, Peterson KL, Reeves TJ, Williams DO, Winters WL. Guidelines for percutaneous transluminal coronary angioplasty: a report of the AHA/ACC Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). J Am Coll Cardiol. 1988;12:529-545.
Kip KE, Faxon DP, Detre KM, Yeh W, Kelsey SF, Currier JW, for the investigators of the NHLBI PTCA Registry. Coronary angioplasty in diabetic patients: the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Circulation. 1996;94:1818-1825.
Hearn JA, King SB III, Douglas JS Jr, Carlin SF, Lembo NJ, Ghazzal MB. Clinical and angiographic outcomes after coronary stenting for acute or threatened closure after percutaneous transluminal coronary angioplasty: initial results with a balloon-expandable, stainless steel design. Circulation. 1993;88:2086-2096.
Ellis SG, Savage M, Fischman D, Baim DS, Leon M, Goldberg S, Hirshfeld JW, Cleman MW, Teirstein PS, Walker C, Bailey S, Buchbinder M, Topol EJ, Schatz RA. Restenosis after placement of Palmaz-Schatz stents in native coronary arteries. Circulation. 1992;86:1836-1844.
Silva JA, Escobar A, Collins TJ, Ramee SR, White CJ. Unstable angina: a comparison of angioscopic findings between diabetic and nondiabetic patients. J Am Coll Cardiol. 1995;92:1731-1736.
Lafont A, Guzman LA, Whitlow PL, Goormastic M, Cornhill JF, Chisolm GM. Restenosis after experimental angioplasty: intimal, medial, and adventitial changes associated with constrictive remodeling. Circ Res. 1995;76:996-1002.
Kakuta T, Currier JW, Haudenschild CC, Ryan TJ, Faxon DP. Differences in compensatory vessel enlargement, not intimal formation, account for restenosis after angioplasty in the hypercholesterolemic rabbit model. Circulation. 1994;89:2809-2815.
Post MJ, Borst C, Kuntz RE. The relative importance of arterial remodeling compared with intimal hyperplasia in lumen renarrowing after balloon angioplasty: a study in the normal rabbit and in the hypercholesterolemic Yucatan micropig. Circulation. 1994;89:2816-2821.
Mintz GS, Popma JJ, Pichard AD, Kent SM, Satler LF, Wong SC, Hong MK, Kovach JA, Leon MB. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation. 1996;94:35-43.
Murcia AM, Fallon JT, Fuster V. Smooth muscle cell proliferation does not account for restenosis in diabetic patients. Circulation. 1996;94(suppl I):I-619. Abstract.
Schomig A, Neuman FJ, Kastrati A, Schühlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary artery stents. N Engl J Med. 1996;334:1084-1089.