Long-term outcome of patients with very long stents for treatment of diffuse coronary disease

Interventional Cardiology

Long-term outcome of patients with very long stents for treatment of diffuse coronary disease Yoseph Rozenman, MD, FACC, Adrian Mereuta, MD, David Schechter, MD, FACC, Morris Mosseri, MD, Chaim Lotan, MD, FACC, Hisham Nassar, MD, A. Teddy Weiss, MD, FACC, Yonathan Hasin, MD, Roland Chisin, MD,* and Mervyn S. Gotsman, MD, FACC Jerusalem, Israel

Objectives The study sought to determine the 6-month clinical outcome of patients who underwent implantation of very long coronary stents to treat diffuse disease and/or long dissections and to compare the findings with those reported in the literature for patients who underwent implantation of multiple short coronary stents.

Background New designs of flexible stents enable the implantation of long stents rather than multiple short, older design stents. The initial experience is very promising but the long-term outcome has not been described yet. Methods Fifty-seven consecutive patients in whom 67 long stents (≥30 mm) were successfully deployed were included in this study. Six-month clinical and angiographic follow-up was prospectively collected. Patients with recurrent angina underwent coronary angiography without further testing. Patients who remained asymptomatic at the 6-month follow-up visit underwent positron emission tomographic imaging, and those with results suggestive of ischemia underwent coronary angiography. A combined study end point was defined as death, myocardial infarction, and the need for target vessel revascularization.

Results Only 1 patient (2%) reached a study end point at hospital discharge. An additional 20 patients (total 21 patients [37%]) reached an end point by 6 months. The outcome was not influenced by the clinical presentation (stable or unstable angina) or by the indication for stenting (elective or emergency). Predictors for adverse outcome were multiple stents per narrowing (63% vs 29%, P < .04), and stents smaller than 3.5 mm (49% vs 22%). Narrowing and stent length were not predictive of a study end point in narrowings that were successfully treated by a single long stent. Conclusions Elective stenting provides an effective solution for patients with diffuse coronary disease provided that a single long stent (usually <40 mm) can cover the full length of the narrowing. The results are better when vessels larger than 3 mm are treated. Compared with multiple short stents, implantation of a single long stent is probably at least as effective, and the procedure is quicker and cheaper and thus should be the preferred approach. (Am Heart J 1999;138:441-5.)

Coronary stents are routinely used during angioplasty to improve immediate and long-term results and to overcome acute complications (coronary dissection and abrupt vessel closure).1-4 Most of the reported experience is with stiff, older stent designs that were manufactured only in short length (15 to 20 mm), and most of the treated patients had short narrowings. In cases of long dissections or in some patients with diffuse disease, multiple overlapping short stents are used; however, these procedures are time consuming, From the Cardiology and *Nuclear Medicine Departments, Hadassah University Hospital. Supported by a research grant from the Dr Herbert J. Berman foundation. Submitted February 6, 1998; accepted May 28, 1998. Reprint requests: Yoseph Rozenman, MD, Cardiology Department, Hadassah University Hospital, PO Box 12000, Ein Kerem, Jerusalem, Israel 91120. Copyright © 1999 by Mosby, Inc. 0002-8703/99/$8.00 + 0 4/1/96336

expensive, and are associated with a high rate of restenosis.5-8 The introduction of new, flexible stent designs9-12 enables deployment of longer stents (rather than multiple short ones), and we have recently described the immediate and 1-month outcome of a group of patients who underwent implantation of one of these very long stents (≥30 mm).13 Most of these patients would have required at least 3 short stents if long stents had not been available. This report describes the clinical outcome of these patients at 6 months and compares the findings with those reported for patients with multiple stents.

Methods Patients Fifty-seven consecutive patients in whom a long coronary stent (≥30 mm) was implanted are included in this report. Most patients (80%) were men, and the mean age was 61 ± 11

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Table I. Summary of 6-month clinical outcome (57 patients and 58 narrowings) Death Emergency CABG Late myocardial infarction Angiography for symptoms Restenosis and revascularization Narrowing in another artery PET Imaging Negative Positive Angiography for positive PET Restenosis and revascularization No restenosis Total number of patients with an end point‡

0 1 1 18 14 4 36* 30 6 5† 3 2 21 (37%)

CABG, Coronary artery bypass grafting; PET, positron emission tomography. *1 patient refused PET and angiography despite anginal symptoms. †1 patient with minimal symptoms refused angiography despite a positive PET scan result. ‡End points are death, myocardial infarction, and target vessel revascularization (the symptomatic patient who refused PET and angiography and the minimally symptomatic patient with a positive PET are counted for the analysis as patients with an end point).

1 and 6 months after the procedure. End points for the analysis included death, acute myocardial infarction, and target vessel revascularization by either coronary artery bypass or repeat angioplasty. Patients with recurrent angina pectoris were directly referred for coronary angiography. Those who remained symptom free (or minimally symptomatic) at 6 months underwent positron emission tomographic flow studies with rubidium 82 (at rest and after dipyridamole challenge). Those who had evidence for ischemia were referred for coronary angiography. The decision as to the required therapy after angiography was left for the operator.

Statistical analysis The combined end point of death, myocardial infarction, or target vessel revascularization was used for comparison among groups. To examine the influence of narrowing length and stented segment length 2 subgroups were defined (those below and above the median value) and comparisons were made between these 2 subgroups. Standard statistical tests were used with P < .05 considered significant.

Results years. The indication for angioplasty was stable angina pectoris in 34 patients, unstable angina in 22 patients, and during direct angioplasty for acute myocardial infarction in 1 patient.

Procedure The details of the procedure have been previously published.13 in brief, 67 long stents (≥30 mm) were implanted in 58 narrowings. The following long stents were used: 34 Microstent II (Arterial Vascular Engineering Inc) 30 and 39 mm long; 16 Nir stents (Medinol Ltd, Israel & Boston Scientific) 32 mm long; 4 Flexstent (Gianturco-Roubin, Cook Corp) 40 mm long; and 13 of various length (32 to 49 mm) of the Wallstent (Medivent-Schneider). Our goal was to cover the whole length of the narrowing with a single stent, and we were able to achieve that in 42 narrowings (72%). In the rest of the narrowings additional stents had to be implanted (short or long), and a total of 85 stents were deployed (1.5 stents per narrowing). Long stents were deployed in all vessels: 26 in the right coronary artery, 17 in the left anterior descending artery, 4 in the circumflex, and 20 in saphenous vein grafts. The indication for stenting was emergency (“bailout”) in 25 narrowings (43%), suboptimal result in 19 (33%), and elective implantation in 14 (24%). Stent deployment was performed with standard techniques. High pressure (>14 atm) was used in all cases, and stent sizes were chosen to match normal vessel diameter. Aspirin administration was started in all patients before stenting and was continued indefinitely. Ticlopidine administration (250 mg twice daily) was started immediately after stenting and continued for 1 month. Heparin was continued until the morning after the procedure and low molecular weight heparin (Enoxaparin, 40 mg twice daily) was continued for 3 more days.

Data analysis Follow-up data were prospectively collected in all patients. Patients were evaluated in the outpatient clinic at

Hospital admission and 1-month follow-up As previously reported13 long stents were successfully deployed in all attempts. Only 1 patient had chest pain develop during hospitalization. He underwent repeat angiography that revealed a patent stent; the remainder of his hospitalization was uneventful. One patient had a perforation of a vein graft after insertion of the third of three 39-mm long Microstents. The perforation in the graft was repaired during emergency surgery. There were no other ischemic events during hospitalization or 1-month follow-up; thus only 1 patient reached a study end point by 1 month.

Six-month follow-up Table I summarizes the 6-month outcome. None of the patients died. One patient was free of symptoms 3 months after successful implantation of a Wallstent in a vein graft to the right coronary artery but was then admitted with an acute inferior wall myocardial infarction. He is currently free of ischemic complaints has moderate renal failure, and we elected to not subject him to the risk of repeat coronary angiography. Eighteen patients were referred for angiography before 6 months because of recurrent symptoms. Fourteen had significant restenosis (1 patient had restenosis of 2 stented long narrowings); 1 underwent coronary artery bypass and 13 underwent repeat percutaneous intervention. Those 4 symptomatic patients who did not have restenosis had significant narrowing in another vessel and were treated by coronary angioplasty. One patient had recurrent angina 2 months after angioplasty and elected to continue with medical treatment without any further evaluation. (For analysis

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Table II. Clinical and angiographic predictors of an end point

Patients/narrowings Age (y) Sex Male Female Clinical presentation Stable angina Unstable angina Myocardial infarction Stented vessel Native artery Vein graft Indication for stenting Elective Suboptimal result Bailout Narrowing length (median 35 mm) Below median Above median Stented segment length (median 39 mm) Below median Above median Stent size 2.5 and 3 mm >3 mm No. of stents Single Multiple

With end point (%)

Without end point

21 (37)/22 (38) 62 ± 10

36/36 61 ± 11

15 (33) 6 (50)

30 6

16 (47) 5 (23)

18 17 1

17 (40) 5 (33)

26 10

5 (36) 9 (47) 8 (32)

9 10 17

8 (29) 14 (47)

20 16

7 (32) 15 (42)

15 21

17 (49) 5 (22)

18 18

12 (29) 10 (63)

30 6

P value

.9 .5 .1

.1 .6

.2 .6 .07 .04

this patient was counted as a patient with an ischemic end point.) Thirty-six patients were asymptomatic or minimally symptomatic 6 months after the procedure and underwent positron emission tomographic study. Of the 6 patients with scans positive for ischemia, 5 underwent repeat coronary angiography and 1 elected to continue with medical treatment. (For analysis we counted this patient also as having an ischemic end point.) Of the 5 who underwent angiography only 3 had restenosis and were treated by angioplasty. Thus by 6 months 21 patients (37%) and 22 narrowings (38%) reached a target end point: no deaths, 1 myocardial infarction, 2 coronary artery bypasses, 16 repeat percutaneous revascularizations, and 2 with ischemia who elected to continue with medical treatment. Table II describes the influence of clinical, procedural, and angiographic variables on the rate of reaching a study end point. There was no significant effect of age, sex, the indication for angioplasty, and the indication for stenting on patient outcome. An ischemic end point was achieved in 22% of patients with stents larger than 3 mm and in 49% of those with small size stents (P = .07). Patients with multiple stents had a 63% event rate compared with only 29% of those with a single long stent (P = .04). Because the most important predictor of an ischemic event was

multiple stenting, we repeated the analysis in the subgroup of patients in whom a single stent was long enough to treat the narrowing (Table III). Event rates were twice as common in patients with small stents compared with those with stents larger than 3 mm (38% and 17%, respectively).

Event rate as a function of narrowing and stented segment length To evaluate the effect of these variables we compared the subgroups above and below the median values. Target end point was achieved more frequently in narrowings and stented segment lengths that were above the median value (Table II). However, these were very long narrowings (53 ± 21 mm narrowing length and 54 ± 21 mm stented segment length) that very frequently required more than a single long stent. Narrowings and stented segments below the median value were significantly shorter (27 ± 5 mm narrowing length and 31 ± 2 mm stented segment length, P < .001 for comparisons with values above the median) and were usually treated with a single long stent. Thus to separate between the effects of multiple stenting and actual length, we analyzed the subgroup of patients with a single stent per narrowing (Table III). Event rates for narrowings and stents above and below the median length values were identical despite a sig-

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Table III. Clinical and angiographic predictors of an end point (single stent subgroup)

Patients/narrowings Age Sex Male Female Clinical presentation Stable angina Unstable angina Stented vessel Native artery Vein graft Indication for stenting Elective Suboptimal result Bailout Narrowing length (median 30 mm) Below median Above median Stent length (median 32 mm) Below median Above median Stent size 2.5 and 3 mm >3 mm

With end point (%)

Without end point

11 (27)/12 (29) 60 ± 11

30/30 63 ± 11

10 (29) 1 (17)

25 5

9 (33) 2 (14)

18 12

10 (31) 2 (20)

22 8

4 (36) 3 (21) 5 (28)

7 11 13

6 (29) 6 (29)

15 15

6 (29) 6 (29)

15 15

9 (38) 3 (17)

15 15

P value

.5 .9 .3 .8

nificant difference in the actual length (37 ± 6 mm compared with 25 ± 4 mm narrowing length [P < .001] and 37 ± 3 mm compared with 31 ± 1 mm stent length [P < .001]).

Discussion Percutaneous therapy of long coronary narrowings is one of the current major limitations of percutaneous interventions. Long balloons are helpful to reduce complications when treating such narrowings, but the restenosis rate is unacceptably high (>50%).14,15 The initial outcome of treatment of diffuse disease (especially with calcification) can be improved with rotational atherectomy, but both the immediate complications and restenosis rate increase with lesion length.16,17 Because of the disappointing initial and long-term outcome in treating these narrowings this subset of patients is usually offered coronary artery bypass. In a previous study13 we described our initial experience with the use of long stents in patients with diffuse disease and/or long coronary dissections. The results were very promising (excellent angiographic results and short-term clinical outcome) in different subsets of patient populations: stable unstable angina and acute myocardial infarction, native arteries and vein graft lesions, bailout and elective conditions. The alternative to a long stent is multiple contiguous short stents as described by Mathew et al.8 Immediate success can be achieved in the majority of patients by using multiple short stents or by using a single, or a smaller number, of

.7

.7 .7 .2

long stents even in the setting of severe dissection and abrupt vessel closure.8,13 Comparing our results to those of Mathew et al is difficult because the studies differ in the patients included, stent implantation technique, and the adjunctive pharmacologic therapy. However, 56 (98%) of the 57 patients included in our series with long stents were free of an adverse event at hospital discharge compared with only 37 (82%) of 45 patients with multiple stents.8 Furthermore, there was no case of stent occlusion in our series whereas there were 4 (8.9%) such cases with multiple stents. Additionally, implantation of one of the new designs of long stents is usually easy to perform and is quicker and cheaper compared with an alternative of multiple short stents. The results of the 6-month follow-up are slightly disappointing, with an ischemic end point reached between 1 and 6 months in 20 (35%) of our 57 patients. Our series includes patients with extremely diffuse disease, some of whom required multiple long stents to treat the full length of the diseased segment. The use of multiple stents was associated with higher than 60% event rate. In those narrowings (<35 to 40 mm) that can be treated with a single stent the expected eventfree survival rate at 6 months is approximately 70% and it is better (approximately 80%) when stents larger than 3 mm can be deployed. In the range of narrowing length in which a single long stent can be used (20 to 40 mm) we did not find a significant difference in the outcome when relatively short narrowings and stents were compared with the longer ones. It is also interest-

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ing that when a strategy of covering the whole length of the narrowing is used and an excellent immediate result is achieved, the long-term outcome is not influenced by the indication for angioplasty (stable or unstable angina pectoris) or by the indication for stenting (elective, suboptimal result, or bailout).

Limitations The study includes consecutive patients in whom a long stent was implanted. There were no specific predefined clinical or angiographic inclusion or exclusion criteria. Also, various stent designs were used so that the group of patients was heterogeneous. However, follow-up was careful, complete, and prospectively planned so that the results represent the expected outcome of the current routine use of long stents in patients with coronary artery disease. Additional limitation is the small sample size and the limited statistical power to define subsets with different outcome. Prospective randomized studies are required to define the long-term outcome of specific subsets of patients with long stents compared with multiple short stents or alternative methods of revascularization.

Practical conclusions In patients with diffuse disease in which narrowing length is such that a single stent (usually <40 mm) can cover the full length of the narrowing, elective stenting can be planned with an acceptable long-term outcome, especially when a stent >3 mm can be deployed. Stent length should be longer than the narrowing length so that multiple stents are avoided. Compared with multiple short stents, we believe that a single very long stent is at least as effective as well as quicker and cheaper, and thus should be the preferred approach whenever possible. Multiple long stents should be avoided as a planned therapy for very diffuse disease because of the high rate of long-term adverse ischemic events. However, under emergency conditions (long dissections) long stents are extremely helpful to achieve an excellent immediate result with very few immediate complications. Again, when possible a single stent should be preferred, but when the dissection is very long multiple stents can be used.

References 1. Savage MP, Fischman DL, Schatz RA, et al. Long term angiographic and clinical outcome after implantation of a balloon expandable stent in the native coronary circulation. J Am Coll Cardiol 1994; 24:1207-12.

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2. Fischman DL, Leon MB, Baim DS, et al for the Stent Restenosis Study Investigators. 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. 3. Serruys PW, de Jaegere P, Kiemeneij F, et al for the Benestent Study Group. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489-95. 4. George BS, Voorhess WD, Roubin GS, et al. Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes. J Am Coll Cardiol 1993;22:135-43. 5. Carroza JP Jr, Kuntz RE, Levine MJ, et al. Angiographic and clinical outcome of intracoronary stenting: immediate and long-term results from a large single-center experience. J Am Coll Cardiol 1992; 20:328-37. 6. Colombo A, Maiello L, Almagor Y, et al. Coronary stenting: single institution experience with the initial 100 cases using the PalmazSchatz stent. Cathet Cardiovasc Diagn 1992;26:171-6. 7. Schatz RA, Baim DS, Leon MB, et al. Clinical experience with the Palmaz-Schatz coronary stent: initial results of a multicenter study. Circulation 1991;83:148-61. 8. Mathew V, Hasdai D, Holmes DR, et al. Clinical outcome of patients undergoing endoluminal coronary artery reconstruction with three or more stents. J Am Coll Cardiol 1997;30:676-81. 9. Ozaki Y, Keane D, Ruygrok P, de Feyter P, Stertzer S, Serruys PW. Acute clinical and angiographic results with the new AVE Micro coronary stent in bailout management. Am J Cardiol 1995;76:112-6. 10. Rozenman Y, Lotan C, Mosseri M, Nassar H, Hasin Y, Gotsman MS. Experience with the AVE Microstent in native coronary arteries. Am J Cardiol 1996;78:685-7. 11. Ozaki Y, Keane D, Ruygrok P, van der Giessen WJ, de Feyter P, Serruys PW. Six-month clinical and angiographic outcome of the new, less shortening Wallstent in native coronary arteries. Circulation 1996;93:2114-20. 12. Eeckhout E, Kappenberger L, Goy JJ. Stents for intracoronary placement: current and future directions. J Am Coll Cardiol 1996; 27:757-65. 13. Rozenman Y, Mereuta A, Mosseri M, et al. Initial experience with long coronary stents: the changing practice of coronary angioplasty. Am Heart J 1997;134:355-61. 14. Brymer J, Khaja F, Kraft P. Angioplasty of long or tandem coronary artery lesions using a new longer balloon dilatation catheter: a comparative study. Cathet Cardiovasc Diagn 1991;23:84-8. 15. Tenaglia A, Zidar J, Jackman JD Jr, et al. Treatment of long coronary artery narrowing with a long angioplasty balloon catheter. Am J Cardiol 1993;71:1274-7. 16. Warth DC, Leon MB, O’Neil W, Zacca N, Pollisar NL, Buchbinder M. Rotation a atherectomy multicenter registry: acute results and 6-month angiographic follow-up in 709 patients. J Am Coll Cardiol 1994;24:641-8. 17. Ellis S, Popma J, Buchbinder M, et al. Relation of clinical presentation, stenosis morphology, and operator technique to the procedural results of rotational atherectomy-facilitated angioplasty. Circulation 1994;89:882-92.