Complete or Incomplete Percutaneous CoronaryRevascularization in Patients With Unstable Angina in

Stent Era: Are Early and One-Year Results Different?

Giuseppe Mariani,1 MD, Stefano De Servi,1* MD, Antonio Dellavalle,2 MD, Sergio Repetto,3 MD,Sergio Chierchia,4 MD, Maurizio D’Urbano,1 MD, Alessandra Repetto,5 MD, and

Catherine Klersy,5 on behalf of the ROSAI Study Group

The aim of our study was to evaluate the impact of a strategy of incomplete revascular-ization by PTCA, with or without stent implantation, on clinical outcome of 208 consec-utive patients (171 men) with unstable angina and multivessel coronary artery disease.Mean age of the group was 63.8 6 10.3 years (range, 31–91). Complete and incompleterevascularization was achieved in 49 and 159 patients, respectively. A total of 226 stentswere implanted in 172 patients (1.31 6 0.65 stent per patient), equally distributed betweenthe two groups. Left ventricular ejection fraction < 40% and total chronic coronaryocclusions were significantly more frequent in patients with incomplete revascularizationthan in those with complete (P 5 0.014 and 0.001, respectively). In-hospital MACEoccurred in 10% and 7.5% of patients with complete and incomplete revascularization,respectively (P 5 NS). By multivariate analysis, multiple stent implantation (OR, 5.44; 95%CI, 1.21–24.3), presence of thrombus in the treated lesion (OR, 6.3; 95% CI, 1.53–25.9),Braunwald class III (OR, 4.74; 95% CI, 1.08–20.8), and ad hoc PTCA (OR 4.51; 95% CI,1.11–18.3) were significantly related to in-hospital outcome. At 1-year follow-up, 11.3%and 11.5% of patients with complete and incomplete revascularization, respectively, hadMACE. In all patients, diabetes (OR, 3.40; 95% CI, 1.09–10.58) and presence of thrombusin the treated lesion (OR, 3.48; 95% CI, 1.12–10.84) were significant predictors of 1-yearoutcome by multivariate analysis. These results indicate that the strategy of incompleterevascularization in unstable angina patients with multivessel coronary disease does notexpose them to a higher risk of death or other major ischemic events in comparison tothose undergoing complete revascularization. Cathet Cardiovasc Intervent 2001;54:448–453. © 2001 Wiley-Liss, Inc.

Key words: incomplete revascularization; stent; unstable angina

INTRODUCTION

Thanks to technological improvements and increasedability of interventional cardiologists, strategies of ag-gressive percutaneous revascularization have been devel-oped for the early management of critical patients withunstable angina and multivessel coronary artery disease.Nevertheless, complete revascularization may be plannedand attempted in only a minority of patients treated withpercutaneous transluminal coronary angioplasty (PTCA),mostly because of the presence of one or more chronictotal occlusions that cannot be successfully crossed over[1]. Secondly, incomplete revascularization may be atherapeutic choice of the operator who decides a priori totreat only the lesion thought to be responsible of theclinical status of the patient. Some early nonrandomized,retrospective studies evaluated the relative merits ofcomplete and incomplete percutaneous revascularizationof patients with multivessel coronary disease without

uniform conclusions about the role of an initial incom-plete revascularization on the clinical outcome [2–7].

The aim of our study was to evaluate the effect ofPTCA on in-hospital and 1-year incidence of adverse

1Unita Operativa di Cardiologia, Ospedale Civile di Legnano,Legnano, Italy2Unita Operativa di Cardiologia, Ospedale Civile S. Croce diCuneo, Cuneo, Italy3Unita di Cardiologia Interventistica, Ospedale di Circolo diVarese, Varese, Italy4Unita Operativa di Cardiologia, Ospedale S. Raffaele, Milano,Italy5Unita Operativa di Cardiologia and Direzione Scientifica, Poli-clinico S. Matteo, Pavia, Italy

*Correspondence to: Dr. Stefano De Servi, U.O. di Cardiologia,Azienda Ospedaliera “Ospedale Civile di Legnano,” Via Candiani 2,20025 Legnano, Italy. E-mail: emodinamica.legnano@calcol.it

Received 10 October 2000; Revision accepted 28 July 2001

Catheterization and Cardiovascular Interventions 54:448–453 (2001)

© 2001 Wiley-Liss, Inc.

ischemic events in a series of consecutive patients withunstable angina and multivessel coronary disease whoentered a multicenter registry in an era of free use ofstent.

MATERIALS AND METHODS

The study population consists of a subgroup of pa-tients with multivessel disease enrolled in the ROSAIregistry, which prospectively monitored consecutive un-stable angina patients who underwent both percutaneousand surgical revascularization between April 1997 andApril 1998 at 14 invasive cardiology centers in northernItaly. Inclusion criteria were new onset of angina (, 2months), recent deterioration in stable angina with symp-toms occurring during minimal effort, or early postin-farction angina. ECG changes were defined as transientor persistent ST segment depression, transient (, 30minutes) ST segment elevation of. 1 mm in at least twocontiguous leads, and isolated changes in T-wave vector.Exclusion criteria were ongoing myocardial infarctionand previous PTCA or coronary artery bypass graft sur-gery (CABG). According to the purpose of the presentstudy, only patients with multivessel disease undergoingPTCA have been selected. Informed written consent wasobtained from all patients.

Coronary arteriography was performed in multipleprojections by Judkins technique. The ejection fractionwas calculated by area-length method from ventriculo-grams performed in 30° right anterior oblique projection.PTCA procedures were performed using monorail cath-eter system with low-profile dilatation balloon. All pa-tients were pretreated with aspirin (160 mg/day at least).At the beginning of the procedure, an intravenous bolusinjection of 10,000 IU of heparin was given and anintraprocedural value of activated clotting time (ACT;Hemotec). 300 sec was recommended. The use of stentand/or elective infusion of abciximab and the choice ofhow many lesions to treat were left to the decision of thecardiologist performing the procedure. Postproceduralmedical therapy consisted of aspirin 160 mg/day indefi-nitely and ticlopidine 500 mg/day for 4 weeks.

Definitions

Refractory angina was defined as recurrent ischemicpain at rest, documented by electocardiographic changescompatible with myocardial ischemia, that occurred dur-ing treatment with at least two anginal drugs, one ofwhich had to be intravenous nitrate, plus aspirin andheparin (all drugs being started at least 2 hr previously).

Prolonged angina was defined as chest pain lastingmore than 20 min. All efforts were done in order tostabilize patients with intravenous and oral medications

before coronary angiography, which was indicated asurgent in case of failure of medical therapy.

Multivessel coronary artery disease was defined as thepresence of a significant stenosis (. 50% luminal nar-rowing) in more than one major epicardial coronaryartery.

The culprit coronary lesion was identified on the basisof electocardiographic changes, angiographic complexityof the lesion, and regional abnormalities of left ventric-ular kinesis. All lesion attempted were described accord-ing to the modified American College of Cardiology/American Heart Association classification [8]. Thepresence of intraluminal thrombus was also reported.

Ad hoc PTCA was defined as a procedure performedimmediately after coronary angiography, due to eitherclinical emergency or the operator’s or patient’s prefer-ence, or to logistic reasons.

Elective PTCA was defined as a procedure performedwithin a few days from the diagnostic study and possiblybefore discharge; in those patients ticlopidine 250 mg bidwas started at least 2 days before PTCA.

Complete revascularization (CR) was defined as suc-cessful management of all significant stenoses in majorepicardial vessels, while incomplete revascularization(IR) was defined as the residual presence of. 50%stenosis in a major segment after the procedure.

Procedural success was defined as a final residualdiameter stenosis of, 30% achieved without the occur-rence of any ischemic event during the initial hospital-ization.

Follow-Up Information

All patients were evaluated during hospital stay and bya hospital visit at 1 year after the percutaneous procedureto asses for any major adverse cardiac events (MACE),defined as death, acute nonfatal myocardial infarction,and need for new revascularization procedure. Death wasdefined as any death regardless of cause. A Q-wavemyocardial infarction was defined as new pathologicalQ-waves on the ECG in conjunction with elevation increatine-kinase greater than twice the upper limit ofnormal. A non–Q-wave myocardial infarction was de-fined by an elevation of the cardiac enzymes greater thantwice the upper limit of normal without the developmentof new pathological Q-waves. Repeat revascularizationreferred to any revascularization procedure (percutane-ous or surgical) performed during the study period.

Statistical Analysis

Continuous variables were expressed as mean andstandard deviation. Categorical variables were expressedas absolute or relative frequencies. Basal characteristicswere compared between patients with and without com-plete revascularization by means of Fisher’s exact test or

Outcome After Incomplete Revascularization 449

Mann-Whitney U-test. In order to assess the predictivevalue of a series of candidate prognostic factors both forhospital and 1-year major cardiac events, logistic modelswere fitted. At multivariate analysis, all variables show-ing aP , 0.1 were included in the model, after checkingfor the presence of colinearity, in addition to the groupindicator for incomplete revascularization. Boostrap val-idation of the model showed a fair predictive value forthe in-hospital events model (discrimination, 0.81; cali-bration, 0.63) and a weaker predictive value for the1-year events model (discrimination, 0.66; calibration,0.65). A P , 0.05 has been retained for statistical sig-nificance. Stata 6.0 (StataCorp, College Station, TX) hasbeen used for computation.

RESULTS

Patients Characteristics

Among 987 patients with unstable angina enrolled inthe ROSAI registry, 208 patients with multivessel coro-nary artery disease underwent PTCA and form the pop-ulation of the study. Mean age of the group was 63.8610.3 years (range, 31–91); there were 171 men and 41women. Thirty-six patients had diabetes (17%), 92 pa-tients had prior myocardial infarction (44%), and one-third of patients had refractory angina. PTCA was per-formed immediately after coronary angiography in 110patients.

Angiographic and Procedural Characteristics

There were 49 patients with complete and 159 patientswith incomplete revascularization (Table I). Lesions inthe left anterior descending artery were treated in 162patients, 41% of them located in the proximal segment. Atotal of 226 stents were implanted in 172 patients with amean of 1.316 0.65 stents per patient equally distributedbetween the two groups. Sixteen percent of patientsunderwent multiple stent implantation. Nine percent ofpatients had a left ventricular ejection fraction, 40%, allof them having incomplete revascularization (P 5 0.014vs. complete revascularization). Thirty-five percent ofpatients had one or more total coronary occlusions witha greater incidence in those with incomplete than in thosewith complete revascularization (41% vs. 14%;P 50.001). Other clinical and angiographic variables wereequally distributed between the two groups of patients(Table I). Abciximab was used in a limited subset ofpatients (7.3%) without difference between two groups.

Follow-Up Events

In-hospital MACE occurred in 10% of patients withCR and in 7.5% of those with IR (P 5 NS). By multi-variate analysis, multiple stent implantation (OR, 5.44;

95% CI, 1.21–24.3), presence of thrombus in the lesiontreated (OR, 6.3; 95% CI, 1.53–25.9), Braunwald classIII (OR, 4.74; 95% CI, 1.08–20.8), and ad hoc PTCA(OR, 4.51; 95% CI, 1.11–18.3) were significantly relatedto in-hospital outcome (Tables II and III).

At 1-year follow-up, 26 more MACE occurred in other22 patients (11.5%): 11.3% and 11.5% of those with CRand IR, respectively, had clinical events (P 5 NS). In allpatients, diabetes (OR, 3.40; 95% CI, 1.09–10.58) andpresence of thrombus in the lesion treated (OR, 3.48;95% CI, 1.12–10.84) were significant predictors of1-year incidence of ischemic events by multivariate anal-ysis. No relation was found between type of revascular-ization and follow-up clinical events (Tables IV and V).

DISCUSSION

The results of our study indicate that the extent ofinitial percutaneous revascularization does not seem toinfluence in-hospital and 1-year outcome of patients withunstable angina and multivessel coronary disease. Thestrategy of dilating and stenting only the lesion respon-sible of ischemic symptoms did not expose such patientsto a greater incidence of death or other major ischemicevents in comparison to those undergoing complete re-vascularization. As in previous works, total coronaryocclusion rate and poor left ventricular ejection fraction

TABLE I. Clinical and Angiographic Characteristics ofUnstable Angina Patients With Complete and IncompleteRevascularization*

Completerevascularization

(n 5 49)

Incompleterevascularization

(n 5 158) P

Age (year) 63.76 10 63.96 11 NSFemale sex 13 (26.5%) 27 (17%) NSBranwald class III 18 (37%) 82 (52%) NSRefractory angina 16 (33%) 52 (33%) NSPrior MI 18 (37%) 74 (47%) NSDiabetes 13 (26%) 23 (14.5%) NSLAD disease 37 (75%) 123 (78%) NSProximal LAD disease 19 (40%) 65 (41%) NSPatients with$ 1 total

occlusions 7 (14%) 65 (41%) 0.001Three-vessel CAD 22 (45%) 80 (51%) NSEF , 40% 0 17 (11%) 0.014Ad hoc PTCA 27 (55%) 82 (52%) NSStent implantation 41 (84%) 131 (83%) NSMultiple stents 9 (19.5%) 24 (15%) NSB2-C type lesions 26 (54%) 87 (55%) NS

*Prior MI 5 prior myocardial infarction; Ad hoc PTCA5 percutaneouscoronary angioplasty performed immediately after coronary angiography;LAD 5 left anterior descending coronary artery; CAD5 coronary arterydisease; type B2-C5 lesion as defined by American College of Cardiol-ogy/American Heart Association; EF5 left ventricular ejection fraction.

450 Mariani et al.

have been major causes of incomplete revascularization[2,3].

The relative value of incomplete vs. complete per-cutaneous revascularization has been analyzed in aseries of nonrandomized retrospective studies [2–7].In these early experiences, the mean percentage ofcomplete revascularization resulted as low as 50%,due to the presence of total coronary occlusions orinability to revascularize large areas of myocardium atrisk [7]. Annual rate of death or myocardial infarctionwas similar between patients with complete and in-complete revascularization, but in the latter groupsurvival free from ischemic events was quite low(60%–70%) because of recurrence of symptoms andneed of new revascularization procedures. Beside in-completeness of revascularization, restenosis and pro-gression of disease in coronary segments other thanthose treated have been supposed to be responsible forthe greater incidence of recurrent ischemia and repeatrevascularization. More recently, Kurbaan et al. [9]checked the role of restenosis on the incidence ofclinical events in the CABRI study. They observedthat 1-year survival was similar between patients un-dergoing PTCA without restenosis at follow-up andthose surgically treated. Nevertheless, the incidence ofangina and need for repeat revascularization washigher in the PTCA group than in the CABG patients,the higher frequency of residual disease after PTCAbeing the major contributor to worse morbidity.

It has been suggested that incomplete anatomical butcomplete functional revascularization may result in out-comes similar to those of complete anatomic revascular-ization [5,6]. The BARI trial allowed for an unbiasedprospective evaluation of the outcome of patients withintended incomplete revascularization randomly as-signed to PTCA or CABG, as well as a nonrandomizedcomparison of outcome between patients with completeand incomplete revascularization [10]. The analysis ofthese data supports the hypothesis that experiencedPTCA operators may determine a priori which clinicallyimportant lesions should or should not be attempted forrevascularization of nondiabetic patients with multives-sel disease, without compromising 5-year survival andwith a borderline increase of likelihood to repeat revas-cularization for recurrent angina.

All the above quoted studies were conducted in anera in which new devices were not yet approved forclinical use or their use was discouraged in some trials.Subsequently, widespread use of stents made it possi-ble to obtain better acute results and to reduce bothrestenosis rate and the need for repeat revasculariza-tion during long-term follow-up [11–13]. Mathew etal. [14] managed 428 lesions in 175 symptomaticpatients with a mean of 1.36 0.8 stents per vessel.The angiographic success rate was 100%; completerevascularization was achieved in 100 patients(57.1%). The Kaplan-Meier probability of survivalfreedom from death, myocardial infarction at 12months was 96.6%, and the likelihood to repeat revas-cularization was 18.3%, which is comparable to thatobserved in other unselected series of multivesselstenting [15]; it is higher than with single-vessel stent-ing [16] but lower than that reported in randomizedrevascularization trial of multivessel coronary diseasetreated with conventional balloon angioplasty [17].We recently published the results of 1-year clinicalfollow-up of 377 patients with multivessel coronaryartery disease prospectively enrolled in a multicenterregistry that collected 939 patients undergoing suc-cessful PTCA and stenting [18]. Only 15% of mul-

TABLE III. Variables Considered in Multivariate LogisticRegression Analysis for In-Hospital Outcome

OR 95% CI P

Age 0.9 0.93–1.05 0.85Refractory angina 0.80 0.15–4.09 0.79Braunwald class III B, C 4.74 1.08–20.8 0.039Ad hoc PTCA 4.51 1.11–18.3 0.035Multiple stents 5.44 1.21–24.3 0.027Thrombus in the culprit plaque 6.30 1.53–25.9 0.011Stent length. 15 mm 4.88 0.79–29.9 0.08Multivessel disease 6.07 2.02–11.3 0.001

TABLE II. In-Hospital Major Adverse Cardiac Events

Total

Completerevascularization

(n 5 49)

Incompleterevascularization

(n 5 158) P

Patients with events 17 5 (10%) 12 (7.5%) NSSubacute occlusion 8 (3.8%) 1 (2%) 7 (0.4%) NSUrgent CABG 2 (0.95%) 0 2 (1.2%) NSUrgent re-PTCA 6 (2.8%) 1 (2%) 5 (3.1%) NSDeath 2 (0.95%) 0 2 (1.2%) NSAcute MI 9 (4.3%) 4 (8.1%) 5 (3.1%) NSBleeding complications 3 (1.4%) 1 (2%) 2 (1.2%) NS

Outcome After Incomplete Revascularization 451

tivessel disease patients had complete revasculariza-tion. The best 1-year outcome was observed in 229patients with one vessel treated and one stent im-planted versus those with single- or multivessel dis-ease treated with multiple stents (14.4%, 23.9%, and23.2% event rates, respectively). Finally, it is interest-ing to note that the presence of thrombus in the culpritlesion was a significant predictor of both early and1-year adverse coronary events. It seems thereforelikely that morphologic characteristics of unstableplaques are more important for determining outcomethan the extent of coronary artery disease.

Even with the limitations of a nonrandomized study,this study reflects the decision-making process in dailypractice regarding revascularization strategies for un-stable angina patients treated in interventional cardi-ology centers of northern Italy. The choice of incom-plete revascularization in unstable patients withmultivessel disease does not seem to expose them to ahigher risk of death or other major ischemic events incomparison to those undergoing complete revascular-ization, not only in the acute setting but also at 1-yearfollow-up.

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TABLE V. Variables Considered in Multivariate LogisticRegression Analysis for 1-Year Outcome

OR 95% CI P

Male sex 0.43 0.13–1.34 0.14Diabetes 3.40 1.09–10.58 0.035LAD 3.01 0.58–15.51 0.187Thrombus in the culprit plaque 3.48 1.12–10.84 0.031Braunwald class III 0.59 0.20–1.67 0.3Refractory angina 1.89 0.57–6.24 0.2

TABLE IV. Major Adverse Cardiac Events at 1-Year Follow-Up (26 Events)

Completerevascularization

(n 5 44)

Incompleterevascularization

(n 5 147) P

Patients with events 22 (11.5%) 5 (11.3%) 17(11.5%) NSDeath 2 (1%) 0 2 NSNonfatal MI 2 (1%) 0 2 NSCABG 3 (1.5%) 1 2 NSRe-PTCA 19(9.9%) 5 14 NSRehospitalization 27 (14%) 6 (13.6%) 21 (14%) NS

452 Mariani et al.

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