Results of coronary stenting for unstable versus stable angina pectoris

for Unstable Results of Coronary Stmting Versus Stable Angina Pectoris Antonio Marzoechi, MD, Giancarlo Piovaccari, MD, Cinzia Marrozzini, MD, Paolo Ortolani, MD, Tullio Palmerini, MD, Angelo Branzi, MD, and Bruno Magnani, Coronary artery stenting has been shown to improve the short- and long-tetm results of coronary angioplasty in mainly stable patients with 1-vessel disease, but it is uncertain whether its use in an unstable clinical setting may be safe and useful. To evaluate the stenting efficacy in patients with unstable angina, we retrospectively examined our experience with the palmaz-Schatz balloon expandable stent in 231 consecutive patients. Patients were divided into 2 groups on the basis of symptoms at the time of stent implantation: group U (132 patients) had unstable angina, and group S (99 patients) had stable angina. After stent insertion, patients were treated with anticoagulant or combined antiplatelet therapy. Baseline characteristics of the 2 roups were comparable with the exception of age (i! igher in the unstable group) and angiogmphic characteristics of the target lesions (more unfavorable in unstable patients). In both groups, coronary stenting presented a high procedural success rate. Major in-hospital complications occurred in 9 unstable (6.8%) and in 2 stable (2%) patients (p = NS)

r

e use of the Palmaz-Schatz stent as a routine adjunct to balloon angioplasty increases the angiographic success of the procedure and the residual lumen at the stenotic site; at 6 months it lowers the lesion recurrence and the rate of repeat angioplasty. ‘,* In addition, stent implantation is a useful adjunct to coronary angioplasty in preventing or minimizing complications associated with flow-limiting coronary dissections that cannot be corrected with conventional percutaneous techniques and which were previously correctable only by surgery.3 Stent implantation has not been widely used in patients with unstable angina pectoris based on the assumption that the placement of an inherently thrombogenic stent on the thrombogenic unstable plaque might provoke a thrombotic response with abrupt occlusion of the vessel. In this study, we retrospectively examined our experience with the Palmaz-Schatz balloon expandable stent in a series of 231 consecutive patients to determine the outcome of stenting in the setting of unstable angina.

METHODS Study patients: From January 1994 to December 1995, 963 consecutive patients underwent elective, From the Institute of Cardiology, University of Bologna, Italy. Manuscript received October 28, 1996; revised manuscript received and accepted January 3 1, 1997. Address for reprints: Antonio Marzocchi, MD, lstituto di Malottie, Cardiovascolari Bologna, Azienda Ospedaliera S. Orsola-Malpighi, Via Mossarenti 9, 40138 Bologna, Italy.

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01997 by Excerpta Medico, All rights reserved.

Inc.

MD

and were mainly related to subacute stent thrombosis. In both groups, subacute stent thrombosis mostly occurred in patients treated with anticoagulant therapy (7 of 9 unstable patients, 2 of 2 stable patients). At 6-month follow-up, unstable and stable patients had a similar incidence of death (O%), Q-wave myocardial infarction (O%), and need of coronary artery bypass graft (3.2% vs 4%, p = NS), but coronary angioplasty repetition (4.8% vs 14%, p = 0.027) and target vessel revascularization (6.3% vs 17%, p = 0.019) rates were lower in the unstable group. In conclusion, stent insertion increases the short- and midterm coronary angioplasty ef fectiveness in unstable angina, making it possible to achieve outcomes quite compamble to stable angina. Compared with conventional anticoagulant regimen, combined antiplatelet thempy after placement of coronary stents seems to reduce the incidence of subacute thrombosis also in this clinical setting. 01997 by Excerpta Medica, Inc. (Am J Cardiol 1997;79:1314-1318)

semielective, or urgent coronary angioplasty at our institution. A Palmaz-Schatz endocoronary stent was implanted in 285 patients. Among these patients, 2 groups were retrospectively selected according to the presence of unstable (group U: 132 patients) or stable (group S: 99 patients) angina before the procedure. This classification of stable versus unstable angina was based on a modified Braunwald classification? Unstable angina was defined by new-onset, severe, accelerated, or chest pain at rest despite antianginal therapy (Braunwald class I, II, III).4 Patients with acute myocardial infarction, silent myocardial ischemia, postinfarction myocardial viability treated with coronary angioplasty and stent implantation, or patients receiving stents in coronary artery bypass venous grafts were excluded from this study. Stent Procedure: Coronary angioplasty was performed using the conventional technique. Nitrates, P-blocking agents, and calcium antagonists were used as clinically indicated. All patients were pretreated with aspirin (150 to 300 mg/day). Intravenous heparin (10,000 to 15,000 U) was given at the start of the procedure and supplemented as needed to achieve a target-activated clotting time of 300 seconds. Conventional rapid-exchange balloon catheters were used for angioplasty. The 7-mm (half stent), IO-mm (P104), or the articulated 15-mm (PS153) standard Palmaz-Schatz stents (Johnson & Johnson, Warren, New Jersey) were folded by hand onto the angioplasty balloon. Balloon catheters for the deployment of the stent were chosen with the 0002-9149/97/$17.00 PII SOOO2.9149(97)00131-g

loon coronary angioplasty; and (6) angioplasty of coronary obstruction. Group U Group S Stenting was planned for indications 4, 5, and 6, (n = 132) (n = 99) p Value and unplanned for reasons 1, 2, and 3. After successful stent implantation, 2 different treatments Age (yr) (mean 2 SD) 62 2 9 58 k 10 0.01 Men 103 (78) 80 (81) 0.726 were begun: (1) warfarin to achieve a therapeutic Coronary arteries narrowed international normalized ratio (3 to 3.5) plus endov>50% in diameter enous heparin until the target international normal1 105 (79) 75 (76) 0.598 ized ratio was reached (first period treatment from >l 27 (21) 24 (24) 0.598 Prior myocardial infarction 52 (39) 36 (36) 0.74 January 1994 to December 1994, 110 patients); (2) Prior coronary bypass 5 (AI 8 (8) 0.266 ticlopidine 250 mg twice a day starting immediately Braunwald class after the end of the procedure and continued for 1 I 24(18) month (second period treatment from January 1995 II 73 (55) to December 1995, 121 patients). Aspirin was mainIII 35 (27) Postinfarction unstable angina 16 (12) tained as before, combined with warfarin or ticlopidine. During hospitalization, after the sheath reValues are expressed 05 number (%I. moval, ticlopidine was combined with subcutaneous heparin 12,500 U twice a day. All patients in both treatment regimens continued aspirin therapy for at least 6 months. In group U, 62 patients (47%) and TABLE II Angiographic and Stenting Procedure Characteristics in group S, 48 patients (48%) were treated with oral Group U Group S p Value anticoagulants. Artery site n= 134 n= 105 Definitions and clinical follow-up: Procedural sucLeft anterior descending 70 (52) 54 (52) 0.924 cess was defined by correct placement of the stent, Right 34 (25) 32 (30) 0.344 Thrombolysis in Myocardial Infarction trial 3 flow, Left circumflex 30 (23) 19 (18) 0.626 and residual stenosis of 30 minutes, abnormal Q C 20 (14) A (3) 0.004 waves not present on the baseline electrocardiogram, Occlusion 7 (51 10 (9) 0.314 Prior restenosis 17 (12) 10 (9) 0.558 or an increasein the creatine kinase (CK) concentraPatients n= 132 n = 99 tion to twice the upper limit of normal, with a conSingle,stent implantation 1 17 (89) 81 (82) 0.202 comitant increase in the CK-MB isoenzyme (> 10% 1-Vessel multiple stent 14 (1 1) 13 (13) 0.701 of CK). Major puncture site bleeding was defined as implantation bleeding requiring surgery or blood transfusion. 6 (6) 0.132 Multivessel stenting 2 (1.5) Unplanned stenting 108 (82) 79 (80) 0.828 Adequate revascularization was defined as successBailout stenting 7 (5.3) 6 (61 0.967 ful dilatation of all significant lesions supplying vi0.9OA Adequate revascularization 107 (81) 80 (81) able myocardium. Clinical follow-up data were ob*According to the definition of Ellis et al.’ tained by clinical visit or by telephone contact with Values are expressed as number (%I. the patient. Statisticalanalysis: Data are expressedas mean + SD. Comparison between groups and subgroups intention of obtaining an artery-to-balloon ratio of were made using &i-square analysis. Differences 1:1 to 1:1.2. Stenting inflation pressures were 2 12 were considered significant at p <0.05. atm. If necessary,multiple stentswere used for complete coverageof the areaof dissection. Intravascular RESULTS ultrasound was not used. The arterial sheath was reIn-hospital outcome: The study group consisted of moved when the partial thromboplastin time fell be- 23 1 consecutive patients (mean .age 60 + 10 years; low 60 seconds. After manual compression of the men/women = 3.8) receiving the Palmaz-Schatz groin, done as long as necessaryfor local hemostasis, intracoronary stent. Patientsin both groups presented a pressure bandage was applied. Stents were im- with similar baseline characteristics except for age planted according to the following indications: (1) which was higher in unstable subjects (Table I). suboptimal angiographic result after conventional The angiographic and procedural data are sumcoronary angioplasty (residual stenosis ~30% with- marized in Table II. There was no significant differout delayed runoff); (2) nonocclusive dissection < 15 ence between the groups with respect to the distrimm; (3) bail-out situations (abrupt vessel closure or bution of the target vessel and data regarding the threatened closure defined as ~50% residual steno- stenting procedure. On the contrary, characteristics sis, dissection 215 mm in length, and extraluminal of the target lesions turned out to be more unfavorcontrast with persistent contrast staining after clear- able in unstable patients. Stent implantation was sucence of the dye injection); (4) restenosis after pre- cessful in 98% of group U patients and in 99% of vious angioplasty; (5) de novo lesion with coronary group S patients (Table III). Death did not occur in anatomy considered unfavorable for standard bal- any patient in either group. Myocardial infarction TABLE I Baseline

Characteristics

of the Patients

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TABLE III In-Hospital

Results

Angiographic success Death Qwave myocardial infarction Coronary bypass Subactue thrombosis Major puncture site bleeding Total major complications (death or Q-wave AMI or CABG) Values AMI

are expressed = acute

OS number

myocardiol

Group U (n = 132)

Group S (n = 99)

129 0 6 6 9 3 9

100 (99) 0 2 (2) 0

(98) (4.5) (4.5) (6.8) (2.2) (6.8)

p Value 0.827 0.5 0.083 0.167 0.744 0.167

2 PI 2 121 2 (21

(%.).

infarction;

CABG

= coronary

artery

bypass

graft

Follow-up results: The 6 unstable patients treated with coronary artery bypass graft during the in-hospital phase were excluded from follow-up and all had no symptoms. At 6 months, no death or myocardial infarction had occurred (Table IV). Coronary balloon angioplasty was repeated in.6 group U (4.8%) and 14 group S (14%) patients (p = 0.027). Four group U (3.2%) and 4 group S (4%) patients underwent elective coronary artery bypass (p = NS). Target vessel revascularization was performed in 8 unstable (6.3%) and in 17 stable (17%) patients (p = 0.019). Absence of angina pectoris at the end of follow-up was achieved in 115 group ZT(91%) and in 92 group S (93%) patients (p = NS).

surgery.

DISCUSSION Coronary stents have had a substantial impact on improving the immediate and late outcome of paTABLE IV Six-Month Follow-Up tients treated with balloon angioplasty. The first evGroup S Group U idence of efficacy was demonstrated by Roubin et (n = 126) (n = 99) p Value al3 in patients with acute or threatened closure com0 0 Death plicating percutaneous coronary angioplasty. HowQ-wave myocardial infarction ever, the indications for stent implantation expanded : (3.2) 0.988 Coronary bypass Y(4) in 1994 when the Benestent and Stress trials1*2 14 (14) 6 (4.8) 0.027 Repeat PTCA showed the effectiveness of routine stent use in im8 (6.3) 17 (17) Target vessel revascularization 0.019 11 (8.7) 7 (7.1) End follow-up angina 0.835 proving both the acute and late clinical outcome. In particular, these 2 randomized trials, including prevValues ore expressed 01 number (%). alently stable patients with 1 significant de novo corPTCA = percutaneous transluminal coronary angioplosty. onary lesion, documented an average increase in angiographic success (from 90% to 94%), a reduction with Q waves complicated failed stent implantation in residual stenosis of the target site (from 34% to in only 1 patient (1%) with stable angina (p = NS). 20%), and in lesion recurrence at 6 months (from Unsuccessful stent implantation required emergency 37% to 27%), with use of the Palmaz-Schatz stent bypass surgery in 3 group U patients (2.2%) (p = as a routine adjunct to balloon angioplasty. One of NS): 2 failed bailout stenting for long dissection and the trials demonstrated that the rate of repeat angio1 stent coronary embolization. Nine group U (6.8%) plasty was reduced from 23% to 14%.’ Neither trial and 2 group S (2%) patients had subacute thrombosis showed any difference in mortality, Q-wave myoof the stent (p = NS). In group U, 4 patients (3%) cardial infarction, or emergency bypass surgery eiwith thrombosis were successfully treated with cor- ther acutely or at 6 months of follow-up. Conventional coronary angioplasty in patients onary angioplasty and 3 (2.2%) with emergency coronary artery bypass. In both group S patients, sub- with refractory unstable angina has higher rates of acute thrombosis was successfully recanalized with mortality (up to 5.4%), myocardial infarction (up to coronary angioplasty (2%). Nevertheless, subacute 9%), and emergency surgery (up to 12%) than in thrombosis induced myocardial infarction in 6 more stable clinical conditions.6-14 The restenosis (4.5%) group U and in 1 (1%) group S patient (p = rate also is higher (range 25% to 37%)6-‘4. The NS). Subacute stent thrombosis occurred most often higher incidence of major complications in unstable in patients taking oral anticoagulants: 9 of 110 angina is probably related to the additional balloon (8.1%), warfarin treatment; 2 of 121 (1.6%), com- injury of the already ruptured unstable lesion conbined antiplatelet treatment (p = 0.044). In unstable taining thrombus.‘5-‘7 The presence of thrombus in coronary lesions has patients the subacute thrombosis rate was 11% (7 of 60) and 2.8% (2 of 69) during the anticoagulant and been identified as a risk factor for adverse outcome combined antiplatelet treatments, respectively (p = during coronary balloon angioplasty.” In this set0.109). Most of the major unstable group compli- ting, stent placement may present increased risk of cations (death, myocardial infarction, emergency stent thrombosis due to the adjunctive intrinsic coronary artery bypass) were related to stent sub- thrombogenicity of the metallic surface of the deacute thrombosis, and occurred most often in the vice. Using multiple logistic regression analysis in a group treated with anticoagulant therapy (5 [8.3%] statistical model consisting of several clinical and vs 1 [ 1.4%], p = 0.152). Total major complications angiographic factors, Nath and colleagues” reported were higher in unstable than in stable patients, but the risk of subacute stent thrombosis to be 11 times the difference did not reach statistical significance higher in patients with unstable angina. Despite high (6.8% in group U, 2% in group S, p = 0.167) inflation pressures in our unstable patients, we de(Table III). tected an increased rate of stent subacute thrombosis 1316

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(6.8%). Most of the patients with unstable angina presenting with stent thrombosis (7 of 9) were in the anticoagulant treatment group. This finding, in agreementwith other studiesmainly involving stable cases,*’ shows that also in this clinical setting, characterized by plaque disruption and intracoronary thrombosis, conventional anticoagulant therapy is less efficacious than combined antiplatelet treatment. In particular, our study showed a striking differencein stent subacutethrombosis (11% vs 2.8%) and major related complication (8.3% vs 1.4%) rates between the 2 treatments in patients with unstable angina. Notwithstanding the relatively high subacute thrombosis rate, our data show that, by allowing the achievement of a higher lumen diameter, stent implantation can improve the efficacy of coronary angioplasty in patients with unstable angina. In fact, our unstable subjects undergoing stent implantation had an overall in-hospital complication rate of 6.8%, with 4.5% Q-wave myocardial infarction, 4.5% coronary artery bypass, and 0% mortality. These percentagesare at the lower end of the spectrumof rates reported with conventional angioplasty6-14and are comparable to those reported with stenting by Malosky et al*l in the same clinical setting. Moreover, according to our data, more favorable results could be obtained with a larger administration of combined antiplatelet therapy. Thanks to the high rate of adequate revascularization (8 1%) and the probably low percentageof restenosis(target vesselrevascularization 6.3%), unstable patients had low rates of clinical events (0% death and Q-wave myoc,ardialinfarction, 3.2% need of coronary artery bypass graft, 4.8% need of repeat coronary angioplasty, absenceof angina at 6 month in 9 1% of patients), even at midterm follow-up. It is likely that, owing to the possibility of sealing intimal dissection against the vessel wall and of achieving a larger luminal diameter, coronary stenting makes it possible to enhance the safety and the short midterm effectiveness of angioplasty also in patients with complex lesions. In contrast to previous studies regarding conventional coronary angioplasty, we found small and not statistically significant differences with intracoronary stenting in immediate and midterm clinical outcome in patients with unstable versus stable clinical status.10J2-14 At midterm follow-up, unstable patients not only had a low percentageof clinical unfavorable events, but also had lower rates of coronary angioplasty repetition and target vessel revascularization than stable patients. Unlike the application of stents, no other device has shown significant advantages when compared with conventional angioplasty in unstable angina. In particular, the results of directional coronary atherectomy in a subanalysis of the Coronary Angioplasty Versus Excisional Atherectomy Trial study*’ showed that unstable patients treated with directional coronary atherectomy had a higher adverse coronary event rate in the acute phase and at followup. In contrast, unlike most interventional devices, adjunctive treatment with antiplatelet GP IIbAIIa re-

ceptor blockers (c7E3 Fab) has shown favorable results. In fact, in the Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications trial, the use of c7E3 Fab demonstrated a great potential in reducing abrupt closure during coronary balloon angioplasty23and the need for target vesselrevascularization at midterm followup% in high-risk angioplasty patients. More recently with the use of c7E3 Fab in combination with coronary angioplasty in unstable patients, the Chimeric 7E3 AntiPlateleT in Unstable angina REfractory to standard treatment trial was prematurely halted because of positive interim results.25It seemspossible that by reducing subacutethrombosis, stent implantation combined with the administration of GP IIbIIIa receptor blockers may further improve angioplasty results in unstable angina. Unfortunately, no data on this setting are currently available. 1. Serruys PW, de JaegereP, Kiemeneij F, Macaya C, Rutsch W, Heynrickx G, EmanuelssonH, Marco J, Legrand V, Mateme P, Belardi J, Sigwart U. Colombo A, Gay JJ, van den Heuvel P, D&an J, Morel M. A comparison of balloon expandablestent implantation with balloon angioplasty in patients with coronary artery disease.N Engl J Med 1994;331:489-495. 2. Fisbmau DL, Leon MB, Bairn DS, SchatzRA, SavageMP, PennI, Detre K, Velui L, Ricci D, Nobuyosbi M, Clemsn M, Heuser R, Almond D, Tierstein P, Fish D, Colombo A, Brinker J, Moses I, 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. 3. Roubin GS, Cannon AD, Agrawal SK, Macander PJ, Dean LS, Baxley WA, Breland J. Irmacoronary stenting for acute or threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation 1992;85:916927.

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