(Circulation. 1996;93:400-402.)
© 1996 American Heart Association, Inc.
Articles |
Dressing Up the Palmaz-Schatz Stent
From the Division of Cardiology, Department of Medicine, Rhode Island Hospital, Brown University, Providence, RI.
Correspondence to David O. Williams, MD, Division of Cardiology, Rhode Island Hospital, Providence, RI 02903.
Key Words: Editorials • angioplasty • stents • heparin • coronary disease
 |
Introduction |
|---|
 Top Introduction References |
|---|
We are approaching the 20th anniversary of the first use of coronary balloon angioplasty in humans. This nonsurgical treatment of obstructive coronary atherosclerosis has proved effective in relieving subjective and objective manifestations of myocardial ischemia, with recent clinical trials demonstrating comparability with coronary artery bypass surgery in selected patients with advanced multivessel disease (References 1 through 5 and personal observations). Despite impressive technical refinements of equipment and technique, balloon angioplasty continues to be plagued by three major limitations: (1) inability to treat certain types of coronary lesions, particularly those presenting as chronic total occlusion; (2) the potential of acutely aggravating coronary obstruction by means of coronary dissection, spasm, or thrombosis necessitating emergency coronary bypass surgery or causing myocardial infarction; and (3) recurrence of coronary narrowing 3 to 6 months after initial treatment.
New devices have been developed in response to these shortcomings. Directional atherectomy can remove a component of the obstructive atherosclerotic plaque, but clinical superiority over conventional balloon angioplasty has been questioned.6 7 8 High-speed rotational atherectomy drills plaque and allows treatment of certain coronary narrowings that cannot be treated with a balloon catheter and appears to enhance the effectiveness and safety of conventional angioplasty for patients with complex lesions.9 10 11 Efforts are ongoing to determine whether debulking lesions alone or in conjunction with balloon angioplasty will reduce the chance of lesion recurrence.12 Devices such as direct laser angioplasty, laser-heated balloon angioplasty, and extraction atherectomy have been shown to be feasible techniques, but their marginal utility has been null or minimal.
Coronary stents, percutaneously deployed metallic endovascular prostheses, have had a substantial impact on improving the immediate and late outcomes of patients treated with balloon angioplasty. The first evidence of efficacy was demonstrated by the Gianturco-Roubin stent that is based on a continuous-coil design. This stent is effective in reexpanding selected arteries in which balloon inflation results in excessive local arterial trauma and dissection and exacerbation of coronary narrowing.13 Released commercially during the Desert Storm Campaign, this stent was aptly termed the "Patriot Missile for abrupt coronary occlusion."
Although several additional coronary stents have been developed and implanted in patients, thus far only one has been shown to improve the short- and long-term results potentially achieved by balloon angioplasty alone. The Palmaz-Schatz stent, a balloon-expandable slotted tube, has been evaluated carefully in two randomized clinical trials, Benestent and STRESS.14 15 These investigations demonstrated that the use of the Palmaz-Schatz stent as a routine adjunct to balloon angioplasty on average increased angiographic success from 91% to 95%, increased the stenosis lumen by 21% to 25%, and reduced lesion recurrence at 6 months by 10%. One of the trials demonstrated that the rate of repeat angioplasty was reduced from 23% to 14%. Neither trial showed any difference in mortality, Q-wave myocardial infarction, or the need to perform emergency bypass surgery either acutely or at 6 months of follow-up. Also noteworthy is the remarkable angiographic appearance of the treated coronary arterial segment after placement of the Palmaz-Schatz stent. After stenting, the diseased arterial segment appears normal, as though the obstructive plaque had been eliminated. All of these factors have contributed to the rapid incorporation of the Palmaz-Schatz stent into daily angioplasty practice such that now in many institutions the majority of patients undergoing balloon angioplasty are treated with this device.
It is important to note that the evolution of stent development was not trouble free. The enthusiasm that followed the first reports of feasibility16 was quickly replaced by concern when early treated patient cohorts began to experience stent thrombosis.17 Particularly alarming was the recognition that stent thrombosis frequently presented as acute myocardial infarction rather than the angina pectoris that was the usual manifestation of restenosis. As a result, investigators resorted to unusually aggressive and rigorous protocols for anticoagulation and antithrombotic therapies, which reduced the incidence of stent thrombosis but introduced a new wave of complications related to impaired hemostasis. Accordingly, stent implantation was associated with rates of hemorrhage requiring blood transfusion and need for surgical vascular repair of 4.9% and 3.9%, respectively.17 The need for anticoagulation and the development of bleeding complications resulted in longer hospital stays as well as higher healthcare costs compared with patients treated with balloon angioplasty alone.18 To avoid this "stent legacy," some physicians considered stents as temporary treatments only, indicated for rescuing failed angioplasty and as bridges for elective coronary bypass surgery. It was not until 1994 when the Benestent and STRESS trials demonstrated the effectiveness of routine stent use in improving both acute and late clinical outcome that the indications for stent implantation expanded.
In an attempt to delay or eliminate the requirement for anticoagulation therapy, Serruys and colleagues19 investigated the efficacy and safety of a heparin-coated Palmaz-Schatz stent, and the results of a pilot trial are reported in this issue of Circulation. Considerable effort was directed to ensuring that sufficient heparin would bond to the stent and that the heparin would be active. The Benestent-II Pilot was designed as a sequential, four-phase, uncontrolled observational trial with about 50 patients in each phase. Patient eligibility criteria were similar to Benestent-I to place observed event rates in some perspective. The first three phases of the trial included anticoagulation with heparin and warfarin but with diminishing intensity. The final phase omitted anticoagulation after stent implantation but included oral ticlopidine 250 mg daily.
The authors reported that stent thrombosis was not observed in any patient although 2 patients did experience myocardial infarction after hospital discharge, events that could have been due to stent thrombosis. If these events are considered as end points, the stent thrombosis rate would still be low at 1.0%. The incidence of severe bleeding decreased progressively with each phase, falling from 7.9% to 0%. Hospital stay for patients receiving ticlopidine was half that for anticoagulated patients. Although not the primary focus of the trial, late clinical and angiographic follow-up was also performed. Angiographic evidence of restenosis ranged from 6% to 20% and was lowest in the ticlopidine group. By 7 months, repeat percutaneous transluminal coronary angioplasty was performed in 26 patients (13%) and bypass surgery in 8 (4%). On the basis of these findings, the authors concluded that stent thrombosis does not occur in heparin-coated stents when implanted by current techniques and that the late clinical outcome is "favorable."
Since the implications of this trial are substantial, it is appropriate to examine the validity of its conclusions. Was the patient sample size large enough to correctly determine the event rate? At first glance it would seem that a cohort of 202 patients is too small to accurately determine the true rate for stent thrombosis, which is expected to be <10%. At least two statistical methods, however, can be used to approximate the true event rate for this cohort reported. Calculation of the upper 95% confidence interval based on no observed events for the 202 patients results in a value of 1.5%.20 If the 2 patients who experienced infarction were considered as having stent thrombosis, the method of normal approximation yields a rate of 2.4%.21 Thus, for the types of patients enrolled in the Benestent-I Pilot, even if the heparin-coated Palmaz-Schatz stent does not totally prevent stent thrombosis, the incidence is likely no greater than 2% to 3%. Importantly, this rate is extremely low compared with that reported previously.14 15 22 23
A second concern is whether the investigation convincingly demonstrates that the low rate of stent thrombosis is due to the heparin coating of the stent rather than some other treatment influence. The technique of stent deployment in this pilot trial differed from that of Benestent-I and in fact was not consistent throughout the course of the trial. For example, high-pressure balloon inflation after stent deployment was used in only 43% of patients in phase 1 but in 82% of patients in phase 4. Meaningful differences were also noted in the degree of stent expansion, ie, the minimal lumen diameter after stent deployment. In Benestent-I, mean minimal lumen diameter after stent deployment was 1.44 mm and the acute luminal diameter gain was 0.78 mm. Values in the Benestent-II Pilot were considerably higher at 1.67 and 0.97 mm, respectively. The impact of deployment technique on stent thrombosis was the subject of a recent report indicating that ultrasound guidance and high-pressure balloon use result in a low incidence of stent thrombosis of non-heparin–coated stents even with reduced or absent anticoagulation.24 A randomized clinical trial comparing the use of heparin- versus non-heparin–coated stents with similar deployment methods would be required to tease out the influence of heparin coating.
Not to go unnoticed were the rates of restenosis and repeat revascularization observed in the Benestent-II Pilot. For the entire cohort, the restenosis rate was 13% and for those patients treated with ticlopidine it was only 6%. These extremely low rates of restenosis were paralleled by low rates of repeat revascularization. One wonders whether the low incidence of lesion recurrence was affected by patient selection, the technique for stent deployment, the heparin coating, or combinations of these factors. Nevertheless, the Benestent-II Pilot strongly suggests that the incidence of restenosis reported in Benestent-I and STRESS can likely be reduced further, along with the need for repeat revascularization. The potential contribution of thrombosis to restenosis and the ability of local heparin to retard this process warrant further attention.
There are several implications of the Benestent-II Pilot. First, if intense anticoagulation with associated complications is no longer an aspect of stent usage, then the indications for stenting should be expanded. For the types of patients investigated in STRESS and Benestent-I and II, stenting improves clinical outcome compared with balloon angioplasty alone. If the "dark side" of stenting has been eliminated, only the beneficial effects remain. Logic then suggests that every patient meeting the eligibility criteria of Benestent and STRESS should be treated with a heparin-coated stent and the techniques employed in the Benestent-II Pilot.
Second, do the results of the Benestent-II Pilot apply to all patients potentially suitable for stenting? It is important to note that the patients enrolled in the Benestent-II Pilot were highly selected. Their lesions were discrete, in large native arterial segments, de novo, short, and readily accessible. Multivessel and multilesion stenting were not performed in this or the previously mentioned trials. Basically, the superiority of the Palmaz-Schatz stent over balloon angioplasty was demonstrated only in patients with simple coronary disease. These patients represent a minority of patients in whom stenting is feasible. Whether stenting favorably influences the outcome of patients with more complex coronary disease compared with balloon angioplasty or other techniques is unknown. At present, it is presumptuous to extrapolate the results of these trials to such patients.
Third, can the favorable results observed with heparin coating of the Palmaz-Schatz stent be extended to other stents? A definitive answer to this question requires a head-to-head clinical comparison of one stent with another. Thus far, the results of any such trials have not been published, although several have been initiated or are planned as part of the US Food and Drug Administration regulatory approval process. Since there are considerable differences in configuration and materials among various stents, it is likely that differences in performance will become evident.
It is of interest that some of the Benestent-II Pilot investigators who now bring us more good news about stents are the same ones who initially reported stent thrombosis as a major shortcoming of this new device. This observation highlights the value of clinical investigation not only in identifying problems but also in finding solutions to important issues of cardiovascular disease.
|
Footnotes |
|---|
The opinions expressed in this editorial are not necessarily those of the editor or of the American Heart Association.
|
References |
|---|
|
TopIntroductionReferences |
|---|
1. Rodriguez A, Boullon F, Perez-Balino N, Paviotti C, Liprandi MI, Palacios IF. Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease (ERACI): in-hospital results and 1-year follow-up. J Am Coll Cardiol. 1993;22:1060-1067. [Abstract]
2. RITA Trial Participants. Coronary angioplasty versus coronary artery bypass surgery: the Randomized Intervention Treatment of Angina (RITA) trial. Lancet. 1993;341:573-580. [Medline] [Order article via Infotrieve]
3.
Hamm CW, Reimers J, Ischinger T, Rupprecht HJ, Berger
J, Bleifeld W. A randomized study of coronary
angioplasty compared with bypass surgery in patients with
symptomatic multivessel coronary disease: German
Angioplasty Bypass Surgery Investigation (GABI). N
Engl J Med. 1994;331:1037-1043.
4.
King SB, Lembo JN, Weintraub WS, Kosinski AS, Barnhart
HX, Kutner MH, Alazraki MP, Guyton RA, Zhao X. A randomized
trial comparing coronary angioplasty with coronary
bypass surgery. N Engl J Med. 1944;331:1044-1050.
5. CABRI Trial Participants. First-year results of CABRI (Coronary Angioplasty versus Bypass Revascularization Investigation). Lancet. 1995;346:1179-1184. [Medline] [Order article via Infotrieve]
6.
Topol EJ, Leya F, Pinkerton CA, Whitlow PL, Hofling B,
Simonton CA, Masden RR, Serruys PW, Leon MB, Williams DO, King SB, Mark
DB, Isner JM, Holmes DR, Ellis SG, Lee KL, Keeler GP, Berdan LG,
Hinohava T, Califf RM. A comparison of directional atherectomy
with coronary angioplasty in patients with coronary
artery disease: the CAVEAT Study Group. N Engl
J Med. 1993;329:221-227.
7.
Adelman AG, Cohen EA, Kimball BP, Bonan R, Ricci DR,
Webb JC, Laramee L, Barbeau G, Traboulsi M, Corbett BN, Schwartz L,
Logan AG. A comparison of directional atherectomy with balloon
angioplasty for lesions of the left anterior descending
coronary artery. N Engl J Med. 1993;329:228-233.
8.
Holmes DR Jr, Topol EJ, Califf RM, Berdan LG, Ley AF,
Berger PB, Whitlow PL, Safian RD, Adelman AG, Kellett MA, Talley JD
III, Shani J, Gottlieb RS, Pinkerton CA, Lee KL, Keeler GP, Ellis SG.
A multicenter, randomized trial of coronary angioplasty
versus directional atherectomy for patients with saphenous vein bypass
graft lesions. Circulation. 1995;91:1966-1974.
9. Warth DC, Leon MB, O'Neill W, Zacca N, Polissar NZ, Buchbinder M. Rotational atherectomy multicenter registry: acute results, complications and 6-month angiographic follow-up in 709 patients. J Am Coll Cardiol. 1994;24:641-648. [Abstract]
10. Burkey DC, Sharaf BL, Miele NJ, Williams DO. Superior outcome with rotational atherectomy combined with balloon angioplasty compared to balloon angioplasty alone: results of a case control study. Am J Coll Cardiol. 1995;25:96A. Abstract.
11. Vandormael M, Reifart N, Preusler W, Schwarz F, Störger H, Hofmann M, Klöpper J, Müller S, Haase J. Six months follow-up results following excimer laser angioplasty, rotational atherectomy and balloon angioplasty for complex lesions: ERBAC Study. Circulation. 1994;90(pt 2):I-213. Abstract.
12. Whitlow PL, Cowley MJ, Kunta RE, Williams DO. Study to determine Rotablator and transluminal angioplasty strategy. Circulation. 1995;92(suppl I):I-330. Abstract.
13.
Roubin GS, Cannon AD, Agrawal SK, Macander PJ, Dean LS,
Baxley WA, Breland J. Intracoronary stenting for
acute or threatened closure complicating percutaneous
transluminal coronary angioplasty.
Circulation. 1992;85:916-927.
14.
Serruys PW, deJaegere P, Kiemeneij F, Macaga 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 comparison of balloon expandable stent implantation with
balloon angioplasty in patients with coronary artery
disease. N Engl J Med. 1994;331:489-495.
15.
Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP,
Penn I, Detre K, Veltri L, Ricci D, Nobugoshi M, Cleman M, Heuser R,
Almond D, Tierstein P, Fish D, 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.
16. Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316:701-706. [Abstract]
17. Serruys PW, Strauss BH, Beatt KJ, Bertrand ME, Puel J, Rickards AF, Meier B, Goy JJ, Vogt P, Kappenberger L, Sigwart U. Angiographic follow-up after placement of a self expanding coronary artery stent. N Engl J Med. 1991;324:13-17. [Abstract]
18.
Cohen DJ, Krumholz HM, Sukin CA, Ho KKL, Siegrist RB,
Cleman M, Heuser RR, Brinker JA, Moses JW, Savage MP, Detre K, Leon MB,
Baim DS, for the Stent Restenosis Study Investigators.
In-hospital and one-year economic outcomes after
coronary stenting or balloon angioplasty: results from a
randomized clinical trial. Circulation. 1995;92:2480-2487.
19.
Serruys PW, Emanuelsson H, van der Giessen W, Lunn AC,
Kiemeney F, Macaya C, Rutsch W, Heyndrickx G, Suryapranata H, Legrand
V, Goy JJ, Materne P, Bonnier H, Morice M-C, Fajadet J, Belardi J,
Colombo A, Garcia E, Ruygrok P, deJaegere P, Morel M-A, on behalf of
the Benestent-II Study Group. Heparin-coated Palmaz-Schatz
stents in human coronary arteries: early outcome of the
Benestent-II Pilot Study. Circulation. 1996;93:412-422.
20.
Hanley JA, Lippman-Hand A. If nothing goes
wrong, is everything all right? JAMA. 1983;249:1743-1745.
21. Armitage P, Berry G, eds. Statistical Methods in Medical Research. 3rd ed. Oxford, UK: Blackwell Scientific; 1994:121.
22.
Schatz RA, Baim DS, Leon M, Ellis SG, Goldberg S,
Hirshfeld JW, Cleman MW, Cabin HS, Walker C, Stagg J, Buchbinder M,
Teirstein PS, Topol E, Savage M, Perez JA, Curry RC, Whitworth H, Sousa
JE, Tio F, Almagor Y, Ponder R, Penn IM, Leonard B, Levine SL, Fish RD,
Palmaz JC. Clinical experience with the Palmaz-Schatz
coronary stent: initial results of a multicenter study.
Circulation. 1991;83:148-161.
23. George BS, Voorhees WD, Roubin GS, Fearnot NE, Pinkerton CA, Raizner AE, King SB, Holmes DR, Topol ER, Kereiakes DJ, Hartzler GO. 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;22:135-143. [Abstract]
24.
Colombo A, Hall P, Nakamura S, Almagor Y, Maiello L,
Martini G, Gaglione A, Goldberg SL, Tobis JM.
Intracoronary stenting without anticoagulation
accomplished with intravascular ultrasound guidance.
Circulation. 1995;91:1676-1688.
This article has been cited by other articles:
 |
|
 |
|
  D. Brieger and E. Topol Local drug delivery systems and prevention of restenosis Cardiovasc Res, September 1, 1997; 35(3): 405 - 413. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||