The Year in Interventional Cardiology 2002

THE YEAR IN INTERVENTIONAL CARDIOLOGY 2002

THE YEAR IN INTERVENTIONAL CARDIOLOGY 2002 Edited by

HD WHITE, PJ DE FEIJTER, B MEIER, A COLOMBO, AP BANNING, R SCHRÄDER

CLINICAL PUBLISHING SERVICES OXFORD

Clinical Publishing Services Ltd Oxford Centre for Innovation Mill Street, Oxford OX2 OJX, UK Tel: +44 1865 811116 Fax: +44 1865 251550 Web: www.clinicalpublishing.co.uk Distributed by: Plymbridge Distributors Ltd Estover Road Plymouth PL6 7PY, UK Tel: +44 1752 202300 Fax: +44 1752 202333 E mail: [email protected] © Clinical Publishing Services Ltd 2002 First published 2002 This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.” All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Clinical Publishing Services Ltd A catalogue record for this book is available from the British Library ISBN 0-203-01188-0 Master e-book ISBN

ISBN 0 9537339 7 1 (Print Edition) The publisher makes no representation, express or implied, that the dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publisher do not accept any liability for any errors in the text or for the misuse or misapplication of material in this work Commissioning Editor: Jonathan Gregory Project Manager: Rosemary Osmond

Contents

Contributors

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Part I Pharmacological management of acute coronary syndromes Harvey D White 1.

Risk stratification in acute coronary syndromes L Kristin Newby

2.

Use of glycoprotein IIb/IIIa inhibitors before percutaneous coronary intervention Neal S Kleiman

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3.

Use of antithrombin therapy in patients undergoing percutaneous coronary intervention Derek P Chew

30

4.

Drug management post-percutaneous coronary intervention Mark W I Webster

39

4

Part II Percutaneous coronary intervention in acute coronary syndromes Pim J de Feijter 5.

Percutaneous coronary intervention in ST-segment elevation myocardial infarction Felix Zijlstra

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6.

Early invasive versus early conservative strategy in non-ST elevation acute coronary syndromes Benno Rensing

57

7.

Percutaneous coronary intervention after thrombolytic therapy Frits Bär and George Moschos

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Part III Stents Bernhard Meier 8.

Stent versus angioplasty: indication for stents in stable angina Roby Rakhit and Bernhard Meier

9.

Stent design and coatings Stephan Windecker

102

Carotid and renal artery stenting Nicola Corvaja and Carlo Di Mario

119

10.

91

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Part IV Restenosis Antonio Colombo 11.

Pathophysiology, pharmacology and patient factors in restenosis David P Faxon

140

12.

Management of in-stent restenosis Antonio Colombo and Konstantinos Toutouzas

150

13.

Vascular brachytherapy for restenosis Ron Waksman

170

Part V Cardiac imaging outside the cardiac catheter lab Adrian P Banning 14.

Nuclear cardiology and stress echocardiography Andrew D Kelion

191

15.

3D echocardiography Harald Becher and Dana Dawson

206

16.

Magnetic resonance imaging in coronary artery disease Stefan Neubauer

220

17.

Coronary artery imaging using electron beam CT and multislice CT John McGuire

235

Part VI Contrast agents in interventional cardiology 18.

Recent trial results Rainer Schräder

257

List of abbreviations

261

Index of papers reviewed

267

General index

277

Contributors

ADRIAN BANNING, MD, MRCP, FESC, John Radcliffe Hospital, Oxford, UK. FRITS BÄR, MD, Department of Cardiology, University Hospital Maastricht, Maastricht, The Netherlands. HARALD BECHER, MD, PhD, John Radcliffe Hospital, Cardiac Clinical Centre, Oxford, UK. DEREK CHEW, MB, BS, FRACP, Harvard School of Public Health, Boston, Massachusetts, USA. ANTONIO COLOMBO, MD, EMO Centro Cuore Columbus, Milan, Italy. NICOLA CORVAJA, MD, Centro Cuore Columbus, Milan, Italy. DANA DAWSON, University of Oxford, Cardiovascular Department, John Radcliffe Hospital, Oxford, UK. CARLO DI MARIO, MD, FACC, FESC, Centro Cuore Columbus, Milan, Italy. DAVID FAXON, MD, Cardiology, University of Chicago, Chicago, USA. PIM DE FEIJTER, Erasmus MC, Thoraxcenter, Rotterdam, The Netherlands. ANDREW KELION, DM, MRCP, Department of Cardiology, Harefield Hospital, Harefield, Middlesex, UK. NEAL KLEIMAN, MD, FACC, The Baylor College of Medicine and The Methodist Hospital, Houston, Texas, USA. JOHN McGUIRE, MBBS, FRANZCR, Queensland Diagnostic Imaging, Holy Spirit Northside Hospital, Chermside, Queensland, Australia. BERNHARD MEIER, MD, Swiss Cardiovascular Center, Bern, Switzerland. GEORGE MOSCHOS, MD, Department of Cardiology, University Hospital Maastricht, Maastricht, The Netherlands. STEFAN NEUBAUER, MD, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. KRISTIN NEWBY, MD, Duke Clinical Research Institute, Durham, North Carolina, USA. ROBY RAKHIT, MD, MRCP, Swiss Cardiovascular Center, Bern, Switzerland. BENNO RENSING, MD, Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands. RAINER SCHRÄDER, FSCAI, Medizinische Klinik III-CCB, Frankfurt am Main, Germany. KONSTANTINOS TOUTOUZAS, MD, EMO Centro Cuore Columbus, Milan, Italy. RON WAKSMAN, MD Washington Hospital Center, Washington, DC, USA.

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MARK WEBSTER, MB, ChB, FRACP, FAHA, Green Lane Hospital, Auckland, New Zealand. HARVEY WHITE, DSc, FRACP, FACC, FESC, FAHA, Director of Coronary Care and Cardiovascular Research, Green Lane Hospital, Auckland, New Zealand. STEPHAN WINDECKER, MD, Swiss Cardiovascular Center, University Hospital, Bern, Switzerland. FELIX ZIJLSTRA, MD, PhD, Department of Cardiology, Isala Klinieken, Hospital De Weezenlanden, Zwolle, The Netherlands.

Part I Pharmacological management of acute coronary syndromes

Pharmacological management of acute coronary syndromes

Introduction Worldwide there are increasing numbers of patients presenting with coronary artery disease. These patients require investigation and may require anti-ischaemic, antiplatelet and antithrombotic treatment, revascularization, and secondary preventative measures. When patients present with a non-ST elevation acute coronary syndrome, it is important that they are risk-stratified so that newer therapies can be appropriately targeted. Kristin Newby stresses the importance of the clinical history and examination as well as the baseline electrocardiogram, and reviews the now considerable information available about troponins, showing their value in risk stratification, their correlation with the pathophysiology of complex ulcerated plaques with distal platelet emboli causing myocyte necrosis, and their value in identifying the patients most likely to benefit from low molecular weight heparins, glycoprotein IIb/IIIa inhibitors or revascularization. IIb/IIIa inhibitors have been clearly shown to reduce the rate of periprocedural myocardial infarction (MI) in patients undergoing percutaneous coronary intervention (PCI) and, in a number of trials, pretreatment with IIb/IIIa inhibitors prior to PCI or coronary artery bypass grafting has resulted in a significant reduction in MI. Neal Kleiman reviews several studies concerning the use of IIb/IIIa inhibitors with PCI, including a meta-analysis of eight abciximab trials evaluating the effects of these agents on long-term mortality, the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, the Do Tirofiban and ReoPro Give similar Efficacy (TARGET) trial, the Treat Angina with aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18 (TACTICS-TIMI 18) trial, and a registry study of abciximab readministration. In the ESPRIT trial, the small semi-synthetic molecule, eptifibatide, reduced the composite 30-day end-point of death/MI/ target vessel revascularization. In the TARGET trial, which directly compared two IIb/IIIa antagonists (abciximab and tirofiban), abciximab was shown to be superior to tirofiban in the dosing regimens used. In the registry study of abciximab readministration, profound thrombocytopenia occurred in 2.4% of patients (i.e. a rate approximately four times that seen with first-time administration) and was often a delayed reaction. In the TACTICS-TIMI 18 trial, ‘upstream’ administration of tirofiban combined with an invasive strategy significantly reduced the composite six-month end-point of death/MI/rehospitalization, although mortality alone was not significantly reduced. There is substantial clinical trial evidence supporting the use of antiplatelet therapy in patients undergoing PCI, but clinical trial information on the use of thrombin inhibitors is only just emerging. Derek Chew reviews the pooled analysis from large-scale clinical trials supporting previous clinical guidelines that have

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advocated higher levels of anticoagulation in patients undergoing PCI when heparin alone is used without an adjunctive IIb/IIIa inhibitor. He also reviews studies of low molecular weight heparins which have demonstrated the feasibility of using these agents during PCI without the need for monitoring, and a reanalysis of the data on bivalirudin indicating that this direct thrombin inhibitor may reduce ischaemic and bleeding outcomes more effectively than heparin alone. The evidence supporting the use of low molecular weight heparin and bivalirudin in patients undergoing PCI is still limited, but the studies reviewed herald the next step in the development of optimal antithrombin therapy for patients undergoing PCI. After PCI and stenting, clopidogrel has replaced ticlopidine because of its better safety profile. Mark Webster reviews these data and the Clopidogrel in Unstable Angina to Prevent Recurrent Events (PCICURE) trial, which reported better outcomes when clopidogrel was used prior to PCI and for nine months afterwards. He also reviews the value of traditional myocardial protective therapies such as β-blockers in reducing the incidence of periprocedural MI.

1 Risk stratification in acute coronary syndromes

Introduction The acute coronary syndromes represent a spectrum of coronary artery disease presentations ranging from acute ST elevation myocardial infarction (MI) to unstable angina. Although they share a common pathophysiology of plaque rupture, platelet activation and thrombosis, they are characterized by varying degrees of thrombotic occlusion of the epicardial coronary arteries and distal embolization with small vessel occlusion. Not only does the risk of subsequent cardiac events vary across this spectrum of patients, but also the appropriateness of available treatment strategies and the magnitude of benefit derived from them vary within this group. A number of tools are available to the clinician to identify and risk stratify patients presenting with acute coronary syndromes. The critical first step is the initial history and physical examination. The importance of baseline demographic and clinical information obtained from this first assessment of the acute coronary syndrome patient has been demonstrated previously by several investigators |1,2|. In particular, the age, Killip class, heart rate, and markers of previous or extensive coronary artery disease are key prognostic indicators in most of these analyses. The baseline electrocardiogram (ECG) is the first objective risk stratification tool available to most acute coronary syndrome patients. Not only does it provide the basis for segregating patients into those who are eligible for reperfusion therapy (i.e. those with ST elevation or bundle branch block) and those who are ineligible, but it also provides important short- and long-term prognostic information. Patients who have both ST elevation and ST depression have the highest 30-day death/MI and 6-month mortality risks, followed by those with either one or the other; patients presenting with only T wave inversion have the lowest risk |3|. Importantly, the risk stratification information provided by the baseline ECG remains significant after adjustment for demographic and clinical baseline characteristics. An important question in the assessment of patients with non-ST elevation acute coronary syndromes has been whether the magnitude of ST depression, as opposed to simply its presence or absence, provides further prognostic information. The importance of both baseline and serial measures of markers of myocardial necrosis (particularly creatine kinase [CK]-MB and the troponins) in risk stratification of both ST elevation MI and non-ST elevation acute coronary syndrome patients has been firmly established |4–7|. Furthermore, the magnitude of marker elevation is roughly linearly correlated with the extent of subsequent risk of cardiac events |5–8|.

© Clinical Publishing Services Ltd

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Beyond prognostic significance, the benefit of glycoprotein IIb/IIIa inhibitors and low molecular weight heparins may be particularly prominent in the presence of troponin elevation |9–11|. However, despite the prognostic importance of the troponins and their utility in defining patients who may benefit most from specific therapies, it is recognized that detection of troponins in the serum reflects the presence of myocardial damage. The ultimate goals of marker testing should be to identify high-risk patients early and treat them before necrosis has occurred, and to identify which troponin-negative patients may also be at high risk of subsequent events. Ongoing development of tests for markers of ‘ischaemia’, and evaluation of novel markers such as B-type natriuretic peptide (BNP), C-reactive protein and other markers of inflammation, may ultimately yield tests to fill this current void. The following articles published over the past year were selected to highlight recent developments in each of these areas, and may point the way to prognostic evaluation of the acute coronary syndrome patient in the years to come. Prognostic value of ST segment depression in acute coronary syndromes: insights from PARAGON-A applied to GUSTO-IIb. P Kaul, Y Fu, W-C Chang, et al. J Am Coll Cardiol 2001; 38:64–71. BACKGROUND. The vast majority of acute coronary syndrome patients do not present with ST elevation on their ECG. Those with ST depression have previously been shown to be at higher risk of subsequent cardiac events than patients with T wave inversion, non-specific ECG changes, or normal ECGs. Although at somewhat lower immediate risk of cardiac events, patients with ST depression on their initial ECG have a similar 30-day risk to that of patients presenting with ST elevation |3|. However, little information has been available to define the relationship of the magnitude of ST depression to the extent of subsequent cardiac risk. Using systematic core laboratory interpretation of baseline ECGs from 7889 patients randomized into two large clinical trials (the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network [PARAGON]-A trial and the Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO]-IIb trial), Kaul et al. investigated the relationship between various degrees of ST depression and outcomes in non-ST elevation acute coronary syndrome patients. From this work, they developed a model to define the importance of quantitative ST-segment evaluation in the presence of other clinical predictors of risk. INTERPRETATION. As shown in Fig. 1.1, increased levels of ST depression on the initial ECG were associated with increasingly poor event-free survival in both acute coronary syndromes cohorts. The majority of the risk differential was manifest within the first 30 days after the event. In multivariate modelling, ST depression was the strongest

predictor of the occurrence of one-year mortality, accounting for 35% of the model’s predictive power. Patients with ≥ 2 mm of ST depression were nearly six times as likely to die within one year compared with patients without ST depression (odds ratio [OR] 5.7; 95% confidence interval [CI] 2.8–11.6). Fig. 1.2 shows the strength of ST depression as a predictor of one-year mortality relative to other clinical predictors of risk.

Comment As this study highlights, important information for risk stratification of patients with acute coronary syndromes is provided by information obtained not only from the initial history and physical examination, but also from the baseline ECG. Because these data may be available much earlier than results of cardiac marker testing, quantification of the magnitude of ST depression appears to be a simple and useful tool for

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Fig 1.1 Survival curves corresponding to the categories of no ST depression, 1 mm ST depression and ≥ 2 mm ST depression in the PARAGON-A study |12| (a) and the GUSTO-IIb study |13| (b). Log-rank tests were used to compare the survival curves. All curves were statistically significantly different at P50% or 70% resolution of ST elevation was less frequent in troponin T-positive patients. INTERPRETATION. Troponin-positivity at baseline in patients with ST elevation MI identifies a population of patients with worse short- and long-term outcomes. The underlying pathophysiology associated

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with this relationship of troponin-positivity with outcome seems to be related to a decreased ability to establish TIMI-3 flow and, when TIMI-3 flow is established, a reduced likelihood of establishing adequate tissue-level perfusion.

Comment This paper highlights the fact that, as in the non-ST elevation acute coronary syndromes, an important component of troponin-positivity at baseline and poorer prognosis may be related to microvascular obstruction. An understanding of the pathophysiological mechanisms underlying the poorer prognosis of troponin-positive ST elevation acute MI patients should help to guide the development of Table 1.1 Patient outcomes cTnT-positive (n=64)

cTnT-negative (n=76)

30 Days Death 10 (15.6) 3 (3.9) Cardiac death 8 (12.5) 3 (3.9) Non-fatal reinfarction — 1 (1.3) Target vessel revascularization CABG 5 (7.7) 2 (2.6) PCI 1 (1.6) 4 (5.2) Combined end-point 13 (20.3) 9 (11.8) Long-term Death 12 (18.8) 3 (3.9) Cardiac death 9 (14) 3 (3.9) Non-fatal reinfarction 1 (1.6) 5 (6.5) Target vessel revascularization CABG 9 (14) 3 (3.9) PCI 3 (5) 10 (13.2) Combined end-point 22 (34) 18 (23.7) Values given as absolute counts with relative frequencies in parentheses. Modified from Giannitsis et al. (2001).

OR (95% CI)

P

4.5 (1.1–17.2) 3.5 (0.9–13.7) —

0.02 0.06 0.4

3.1 (0.6–16.7) 0.3 (0.03–2.6) 1.9 (0.7–4.8)

0.2 0.2 0.2

5.6 (1.5–20.9) 3.9 (1.03–15.4) 0.2 (0.03–1.9)

0.005 0.03 0.2

3.9 (1.03–15.4) 0.3 (0.09–1.2) 1.7 (0.8–3.5)

0.03 0.09 0.2

treatment strategies aimed at addressing the deficiencies. However, it must be emphasized that only randomized clinical trials designed to assess the impact of such treatment strategies on clinical outcomes will determine whether targeting a specific pathophysiological mechanism is beneficial in practice. Benefit of glycoprotein llb/llla inhibition in patients with acute coronary syndromes and troponin Tpositive status: the PARAGON-B troponin T substudy. L K Newby, E M Ohman, R H Christenson, et al. Circulation 2001; 103: 2891–6. BACKGROUND. Although previous retrospective assessments had suggested a relationship between troponin status and treatment benefit from IIb/IIIa inhibitors in patients with non-ST elevation acute coronary syndromes |9,10|, the PARAGON-B investigators sought to prospectively quantify this

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relationship. In this study, 1160 patients had troponin T measured at the time of randomization into the main PARAGON-B study. This was a randomized comparison of the effect of the IIb/IIIa

inhibitor, lamifiban, plus heparin with standard heparin therapy for treatment of non-ST elevation acute coronary syndromes. The relationship of troponin status (positive or negative) with clinical outcomes at 30-days and the interaction of troponin status with treatment assignment were assessed. In addition, a meta-analysis of this interaction was performed. As expected and consistent with numerous previous studies, troponin-positive status was associated with worse 30-day outcomes than troponin-negative status. Furthermore, in this prospective assessment, troponin T-positive patients who were treated with lamifiban had significant reductions in the 30-day end-points of death/MI/recurrent ischaemia and death/MI compared with patients who received lamifiban-placebo (Table 1.2). No treatment benefit was observed in patients who were troponin Tnegative. A meta-analysis combining these results with those of previously published evaluations of treatment effect by troponin status in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) study (testing the benefit of abciximab in patients with acute coronary syndromes in whom coronary lesions had been identified and PCI was performed) and the Platelet Receptor Inhibition in Ischaemic Syndrome Management (PRISM) study (evaluating tirofiban for management of patients with acute coronary syndromes) confirmed the consistency and significance of this interaction across all IIb/ IIIa inhibitors |9,10|. Fig. 1.3 demonstrates this relationship. INTERPRETATION. Among patients with acute coronary syndromes, troponin-positive status identifies a high-risk subgroup of patients who derive particular benefit from treatment with intravenous IIb/IIIa inhibitors. It is believed that this association of treatment benefit with troponin-positive status is related to the pathophysiological observations of more complex coronary lesions associated with a greater thrombus burden in troponin-positive patients |15–17|.

Comment This study and those that preceded it have collectively identified troponin status as an important consideration in the decision to use a IIb/IIIa inhibitor for treatment Table 1.2 Clinical outcomes at 30 days by baseline troponin T status and treatment assignment

Death/reinfarction/severe recurrent ischaemia Death/reinfarction Death Reinfarction Severe recurrent ischaemia

Troponin T-positive

Troponin T-negative

Lamifiban (n=227)

Placebo (n=237)

Lamifiban (n=344)

Placebo (n=349)

11.0% 11.0% 3.1% 9.3% 0.4%

19.4% 19.0% 5.1% 17.3% 0.4%

10.8% 9.6% 1.2% 9.3% 1.5%

11.2% 10.3% 2.0% 9.7% 0.9%

Source: Newby et al. (2001).

of non-ST elevation acute coronary syndrome patients. However, such a relationship may ultimately prove too simplistic on the individual patient level. As observed in PRISM and suggested by Antman, the relationship of enhanced treatment benefit with troponin-positive status may be ‘U-shaped’, with a less

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Fig. 1.3 Odds ratios with 95% confidence intervals for death/MI in troponin-negative and troponin-positive patients and for the interaction of troponin status with treatment effect in the PRISM |9|, CAPTURE |10| and PARAGON-B trials, and for these trials combined. The values to the left of 1.0 indicate a benefit of IIb/IIIa inhibition. Source: Newby et al. (2001).

marked benefit at very high or minimally elevated levels (Figs. 1.4 and 1.5) |9,18|. Only further prospective study will definitively resolve this issue. Relationship between interleukin-6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or non-invasive strategy. E Lindmark, E Diderholm, L Wallentin, A Siegbahn. JAMA 2001; 286: 2107–13. BACKGROUND. The role of inflammation in the genesis of atherosclerosis and acute coronary syndromes is increasingly recognized, and markers of inflammatory activity (including C-reactive protein and its inducer, interleukin-6 [IL-6]) have been associated with prognosis both in apparently healthy individuals and in patients with acute coronary syndromes |19–23|. Lindmark et al. performed a prospective substudy of the

Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC-II) study to evaluate the relationship between IL-6 elevation and prognosis in unstable coronary artery disease. Furthermore, they investigated whether, analogous to the situation with troponins and IIb/IIIa inhibitors, elevation of this marker would identify a group for which an early invasive treatment strategy or prolonged treatment with low molecular weight heparin would be particularly beneficial. The design of the FRISC-II study is shown in Fig. 1.6. After five days of standard open-label treatment with either unfractionated heparin or dalteparin, patients were randomized to receive either dalteparin or placebo subcutaneously twice daily for 90 days. Patients who had no contraindications to early coronary angiography were also randomized to early invasive care or a non-invasive strategy. Blood samples for IL-6, troponin T and C-reactive protein were obtained at baseline from all patients. Among medically-treated patients in the randomized invasive versus non-invasive comparison, those with elevated IL-6 levels (≥ 5 ng/ml) had a one-year mortality rate 3.5 times that of patients without elevated

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Fig. 1.4 Adjusted hazard ratios (95% CI) for treatment with tirofiban by troponin I quartiles and troponin T quintiles. The benefit of treatment was defined as a decrease in death/MI at 30-day follow-up. Hazard ratios lower than 1.0 show a benefit for treatment with tirofiban compared with heparin. Source: Heeschen et al. (1999) |9|. IL-6 levels (7.9% versus 2.3%, P