University of Groningen

Towards a tailored approach in Percutaneous Coronary InterventionsWijpkema, Jasper Sjoerd

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Citation for published version (APA):Wijpkema, J. S. (2006). Towards a tailored approach in Percutaneous Coronary Interventions: the role ofnew diagnosic and treatment modalities. s.n.

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Section 3Adjuvant pharmalogical treatment and PCI

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Jasper S. WijpkemaGillian A.J. JessurunAd J. van BovenDik I.K. VersteegRaymond W. HautvastRené A. Tio

Catheter Cardiovasc Interv. 2003 Nov;60:339-43.

Chapter 7Clinical impact of abciximab on long-term outcome after complex coronary angioplasty

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Abstract

Glycoprotein iib/iiia receptor antagonists, such as abciximab, are used to reduce major adverse

cardiac events (mace) in patients undergoing percutaneous transluminal coronary angioplasty

(ptca). The goal of this study was to evaluate the administration of abciximab in relation to

lesion complexity and peri-procedural complications. A total of 357 patients, with 435 de novo

lesions were included in this study. Lesions were divided into simple (type a and type b1) and

complex (type b2 and type c) lesions, according to the American College of Cardiology/American

Heart Association (acc/aha) Task Force lesion complexity system. Abciximab was given to

unstable complex lesions and simple lesions with a peri-procedural unstable complicated course.

The overall incidence of mace during the 9-months follow-up period was 17.0%. Patients

treated with abciximab had a higher lesion complexity (p<0.001), dissections (p=0.014), stents

(p<0.001) and vessels involved (p<0.001). in addition, the abciximab group was characterised

by a higher angina nyha class (p=0.005), lower timi-flow prior to stenting (p=0.01) and a

longer total inflation time (p=0.006). Despite these clinical differences, the occurrence of mace

within the abciximab group was slightly less than in the group without abciximab (16.2%

and 17.3% respectively). Lesion complexity was directly related to mace in the group which

dit not receive abciximab (simple and stable complex lesions; p=0.04). On the other hand, in

subjects treated with abciximab, lesion complexity was not related to a higher incidence of

mace (p=0.76). The use of abciximab equalizes the difference in outcome between simple and

complex lesions. Therefore, abciximab should be advocated especially in unstable and complex

percutaneous coronary interventions.

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Introduction

In 1986 the American College of Cardiology/American Heart Association (acc/aha) Task Force

lesion complexity system was developed to give insight in the suitability of lesions for coronary

angioplasty. 1 In this system, which was modified in 1990, type a or b1 lesions were thought

to have higher success rates and lower procedural risk than type b2 and c lesions (bifurca-

tion, ostial, calcified, large filling defect, chronic total occlusion and degenerated vein graft).

This has also been shown in other studies on this subject. 2 While new techniques and devices

were developed, the importance of this system diminished with regard to the primary success

rate and peri-procedural complications such as death, myocardial infarction, dissection or

thrombosis. 3 In recent studies it was shown that the modified acc/aha lesion morphology

scheme had significant prognostic value. In addition it should be mentioned that the classifica-

tion influences the entire 1-year clinical course.

The clinical implementation of concomitant advanced pharmacological treatment strategies has

further improved the short and long-term efficacy of percutaneous revascularisation procedures.

In the early nineties Glycoproteïn (gp) iib/iiia-antagonists were introduced. It has been shown

that gpiib/iiia receptor blockers, such as abciximab in combination with aspirin, heparin and

ticlopidine, enhance the inhibiting effect on platelet and endothelium activation. The synergistic

effect of these anti-thrombotic drugs has reduced short and long-term complications after per-

cutaneous coronary revascularisation. 4-11 However, gpiib/iiia receptor blockers are expensive

and it remains debatable whether its administration to all patients undergoing percutaneous

coronary intervention is mandatory. Therefore, it is interesting to investigate the clinical impact

from the perspective of daily practice and to assess the role of key factors on long term outcome

such as lesion complexity, patient characteristics and peri-procedural complications.

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Methods

This was a prospective study in patients with successful coronary stent delivery for de-novo

lesions. In the period from January 1999 to November 2000, a total of 2,500 patients under-

went angioplasty, amongst these 417 elective angioplasties of a de novo lesion treated with

one or more stents. Of these patients, 357 gave informed consent for clinical follow-up at the

University Medical Centre Groningen, the Netherlands. Successful stent delivery was defined

as the presence of a stable angiographic result, timi 3 flow after stent delivery and a residual

stenosis of less than 20%. Exclusion criteria were restenotic lesions and co-morbidity that could

hamper adequate follow-up, such as serious disease or malignancy and alcohol or drug abuse.

The study was approved by the institutional review board.

Baseline Angiography and Stent Delivery

Angioplasties were performed by femoral or, in some cases, by radial artery approach.

Two orthogonal projections were taken in each coronary angiogram and analysed by experi-

enced angiographers. The modified acc/aha grading system was used to classify the lesions into

type a, b1, b2 or c lesions. The type of stents used were ave (Medtronic wire hybrid, welded gfx

ii), Multilink (Guidant tubular corrugated ring, ml Tristar or Tetra) and nir (Boston Scientific

welded modified slotted tube, Nir Primo) stents. The scheduled treatment strategy and course of

the procedure was not influenced by participation in the study.

Peri-procedural treatment

All patients received aspirin (500 mg 1 day before; 100 mg/day after stenting) and clopidogrel

(300 mg 1 day before; 75mg/day during 28 days after). Heparin was administered as boluses

of 5,000 iu intravenously to achieve an activated clotting time of 200 seconds, and abciximab

as a bolus of 0.25 mg per kilogram of body weight, followed by 12-hour infusion of 0.125

microgram per kilogram per minute.

Before the procedure, lesion complexity was assessed. The decision to give abciximab was based

on the type of lesion (b2, c), the presence of peri-procedural complications, instability of the

lesion and the final result of the angioplasty (for instance visible thrombus). Unstable lesions

were defined as those simple or complex lesions which showed progressive post-dilatation mor-

phological and functional deterioration, such as thrombus formation, dissection and worsened

timi flow. Based on these criteria abciximab administration was strictly protocolised. However,

the final decision to give Abciximab was left to the discretion of the operator.

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Follow Up

All patients were followed for clinical events during a period of 9-12 months. In addition a

subgroup of patients gave consent at inclusion for a control angiography after 6-9 months

follow-up. Clinical endpoints were death, myocardial infarction, target vessel revascularisation

(tvr; either ptca or cabg of the treated vessel), cerebrovascular events, and major bleeding

(requiring transfusion).

During the follow-up angiography the same two orthogonal projections were taken as in the

baseline angiography. Quantitative coronary angiography (qca) was performed by a previously

described and validated automatic contour detection technique 12 (cms, Medis Co., Nuenen,

the Netherlands and Quantcor qca, pmi-Siemens, Maastricht, The Netherlands). Off-line qca

was performed by an indepen¬dent analyst, not aware of the clinical condition of the patient, to

measure the diameter stenosis of the treated segment. Lesions were considered restenotic if the

target lesion had a 50%, or more, stenosis.

In the cases in which the patient died within 6 months of the first procedure, the cause of death

was determined if possible. All sudden deaths with unknown causes were considered to be

cardiac deaths.

Statistical Analysis

Descriptive statistics are reported as mean ± standard deviation (sd) and percentages. The Chi-

square test was used to compare the groups with the different types of stenosis for cathegorial

variables. The independent samples t-test (2-sided) was used to compare the groups for continu-

ous data. A p-value < 0.05 was considered statistically significant.

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Results

A total of 357 patients scheduled for elective angioplasty were included in this study. The baseline

characteristics of the patients are shown in Table 1. No differences regarding risk factors were

present between patients treated with or without abciximab. All patients were followed for a

period of 12 months for the occurrence of a major adverse cardiac events (mace = Target vessel

revascularisation (tvr), myocardial infarction, and death). A total of 435 lesions were treated:

220 simple and 215 complex lesions. Abciximab was administered in 79 patients. In these 79

patients 99 lesions were treated, the others received standard medication. The differences in

baseline lesion variables between the two groups are shown in Table 2. There were more com-

plex lesions, dissections, extensive coronary artery disease, severe angina pectoris complaints,

stents used and a lower timi-flow before ptca in the abciximab group. There was no significant

difference in inflation pressure and diameter, but the duration of the inflation was longer in the

abciximab group. With multivariate analysis, no difference regarding risk factors were found,

except for the presence of Diabetes Mellitus. Especially in diabetic patients, abciximab reduced

mace from 20.0% to 11.8%.

The overall incidence of mace was 17.0 % (2.8% death and 14.2% tvr). In the abciximab

group the incidence of mace was 16.2% (3.0% death, 13.2% tvr) and in the group without

abciximab mace was found in 17.3% (2.7% death, 14.6% tvr). Only 94 patients agreed with

repeated angiography. The overall angiographic restenosis rate was 18.1%, requiring tvr in

8.5% of the patients. No difference in mace between patients treated with abciximab group

(20.2%: 3.0% death, 17.2% tvr) and without abciximab (19.3%: 2.7% death, 16.6% tvr)

was found. Restenosis rates were 17.2% and 16.4% respectively.

Focusing on all lesions, there were 13.4% mace (2.4% death, 11.0% tvr) in simple lesions

versus 20.4% (3.1% death, 17.3% tvr) in complex lesions (p=0.056). Lesion complexity was

associated with mace, only if patients were not treated with abciximab. In patients treated with

abciximab the outcome of complex lesions was comparable to simple lesions. The negative

difference such as found in the untreated group disappeared (Figure 1).

Table 1. Patient Characteristics (n=357)

Age (yrs.) ± SD 62.16 ± 11.26

Sex (% female) 22.4

Hypertension (%) 38.4

Hypercholesterolaemia (%) 65.8

Diabetes (%) 14.0

Smoker (%) 21.6

Positive family history (%) 31.7

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Figure 1. mace in different lesion types, with and without abciximab

Table 2. Differences in lesion variables of both the groups with and without abciximab.

No Abciximab Abciximab p-value

Complex Lesions (%) 44.64 79.79 <0.001

Dissection (%) 24.11 37.37 0.014

Number of stents (mean) 1.62 2.13 <0.001

Vesseldisease (mean) 1.65 1.97 <0.001

Angina pectoris-class (mean) 3.09 3.3 0.005

TIMI-flow before stenting (mean) 2.68 2.41 0.01

TIMI-flow after stenting (mean) 2.98 2.96 0.244

Maximal diameter (mm) 3.151 3.211 0.355

Maximal pressure used (atm) 12.15 12.01 0.67

Duration of inflation (sec) 85.47 114.4 0.006

Legend Figure 1: The incidence of Major Adverse Cardiac Events (MACE) in relation to lesion complexity (simple = type A or B1 lesion; complex = type B2 or C lesion), with or without abcximab treatment.

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Discussion

The beneficial effect of abciximab in the prevention of cardiac events after coronary interventions

has been widely shown in many studies 4-11 In the first large trial (epic)4 high risk patients were

randomised between abciximab and placebo infusion after balloon angioplasty or atherectomy.

Abciximab infusion reduced the thirty-day cardiac event rate. These data were further extrapo-

lated to low-risk patients (epilog)5, stented subjects (epistent, eraser)6;7, and acs/mi subjects

(rapport, isar-2, admiral, cadillac). 8-11 In all these trials a favourable short-term effect of

abciximab was found. In addition, a recent meta-analysis described a long-term beneficial effect

on survival. 13 While in our study high-risk lesions appeared to benefit, low risk lesions did not

appear to benefit. Nevertheless, considering the previously mentioned studies, one could argue

that standard abciximab-treatment should be administrated to all pci patients. However, since

abciximab is expensive, it would be desirable to identify patients who would benefit most, or

have a higher risk for the occurrence of events after coronary intervention. This study showed

that lesion complexity as a risk parameter could play an important role in determining whether

a patient benefits from abciximab.

The acc/aha classification system has originally been set-up to predict the primary success rates

of balloon angioplasty. However, currently available techniques have equalised the primary

success rates of coronary interventions in simple and complex lesions. It is yet unclear, whether

the classification system has any prognostic value on the long-term outcome in patients with

coronary stent implantations. On this subject, Kastrati et al. found, that patients with complex

(type b2 or c) lesions have a significant higher risk for developing restenosis and adverse events

than patients with simple (type a or b1) lesions. 14 Therefore it is conceivable, that good clinical

practice should be more ardent in the treatment of complex lesions with abciximab. In this study

abciximab was given more frequently to patients with complex lesions and severe underlying

coronary artery disease. In contrast to the study of Kastrati et al., which was performed in the

era before abciximab, we did not find any difference in cardiac events between simple and com-

plex lesion morphology in the total population. Although the study population was relatively

small, this observation may suggest that the daily pattern of abciximab administration such as

described in this high volume interventional cardiology centre harbours beneficial effects on the

clinical performance and overall outcome.

Study limitations

This was a study in a small number of patients, and the use of abciximab was not randomly

assigned. However, abciximab administration was routinely given under pre-defined circum-

stances, as described in the methods. The study set-up can not rule out any bias in abciximab

administration. Nevertheless, this report represents true daily clinical practice of abciximab.

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Clinical implications

In specific subjects, it is good clinical practice to focus treatment strategy on the long-term

outcome. This could defer eventual major cardiac surgery to a later stage. This is an evidence-

based strategy for modern interventional cardiologist. 15 Therefore, the combined strategy of

percutaneous coronary intervention with abciximab may add value to the clinical outcome of

complex symptomatic coronary artery disease. This facilitates individual tailoring of a cost-ef-

fective revascularisation strategy for subjects in current cardiological practice.

Abciximab is more frequently used in complex percutaneous coronary revascularizations, and

eliminates the differences in outcome following the treatment of simple and complex lesion mor-

phology. No beneficial effect appeared to be present in patients with simple lesions. Therefore,

the use of abciximab in daily clinical practice should be advocated especially in unstable and

complex coronary lesions.

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Reference List

Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King SB, Loop FD, Peterson KL, Reeves TJ, Williams DO, Winters WLJ. Guidelines for percutaneous transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation 1988;78:486-502.

Ellis SG, Guetta V, Miller D, Whitlow PL, Topol EJ. Relation between lesion characteristics and risk with percutaneous intervention in the stent and glycoprotein IIb/IIIa era: An analysis of results from 10,907 lesions and proposal for new classification scheme. Circulation 1999;100:1971-1976.

Ellis SG, Vandormael MG, Cowley MJ, DiSciascio G, Deligonul U, Topol EJ, Bulle TM. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Multivessel Angioplasty Prognosis Study Group. Circulation 1990;82:1193-1202.

AnonymousUse of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation. N.Engl.J Med 1994;330:956-961.

AnonymousPlatelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. The EPILOG Investigators. N.Engl.J Med 1997;336:1689-1696.

AnonymousAcute platelet inhibition with abciximab does not reduce in-stent restenosis (ERASER study). The ERASER Investigators. Circulation 1999;100:799-806.

AnonymousRandomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. The EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet 1998;352:87-92.

Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N.Engl.J Med 2002;346:957-966.

Brener SJ, Barr LA, Burchenal JE, Katz S, George BS, Jones AA, Cohen ED, Gainey PC, White HJ, Cheek HB, Moses JW, Moliterno DJ, Effron MB, Topol EJ. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Circulation 1998;98:734-741.

Neumann FJ, Kastrati A, Schmitt C, Blasini R, Hadamitzky M, Mehilli J, Gawaz M, Schleef M, Seyfarth M, Dirschinger J, Schomig A. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction. J Am Coll.Cardiol.2000;35:915-921.

Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S, Villain P, Boulenc JM, Morice MC, Maillard L, Pansieri M, Choussat R, Pinton P. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N.Engl.J Med 2001;344:1895-1903.

Reiber JH, van der Zwet PM, Koning G, von Land CD, van Meurs B, Gerbrands JJ, Buis B, van Voorthuisen AE. Accuracy and precision of quantitative digital coronary arteriography: observer-, short-, and medium-term variabilities. Cathet Cardiovasc Diagn 1993;28:187-198.

Anderson KM, Califf RM, Stone GW, Neumann FJ, Montalescot G, Miller DP, Ferguson JJ, Willerson JT, Weisman HF, Topol EJ. Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention. J Am Coll.Cardiol.2001;37:2059-2065.

Kastrati A, Schomig A, Elezi S, Dirschinger J, Mehilli J, Schuhlen H, Blasini R, Neumann FJ. Prognostic value of the modified american college of Cardiology/American heart association stenosis morphology classification for long-term angiographic and clinical outcome after coronary stent placement. Circulation 1999;100:1285-1290.

Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJ, Schonberger JP, Buller N, Bonser R, van den Brand MJ, van HL, Morel MA, van HB. Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease. N.Engl.J Med 2001;344:1117-1124.

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