This is the current release of the guideline.

Coronary artery disease (CAD) including:

• Acute coronary syndromes (ACS) without ST-segment elevation (unstable angina [UA] or non-ST-segment elevation myocardial infarction [NSTEMI])
• Acute coronary syndrome with ST-segment elevation (ST-segment elevation myocardial infarction [STEMI])

Assessment of Therapeutic Effectiveness
Evaluation
Management
Treatment

Cardiology
Family Practice
Internal Medicine
Thoracic Surgery

Physicians

To give practically oriented recommendations on when to perform percutaneous coronary intervention (PCI) on the basis of currently available published data derived from randomized and nonrandomized clinical studies

Patients with coronary artery disease (CAD)

Percutaneous Coronary Intervention (PCI)

1. Primary PCI (within 12 hours of symptom onset)
2. Rescue PCI (when thrombolysis fails)
3. Emergency (multivessel) PCI (in cardiogenic shock)
4. Routine post-thrombolysis coronary angiography and PCI
5. Ischaemia-guided PCI after successful thrombolysis

Adjunctive Medications

1. Nitroglycerin (NTG)
2. Adenosine
3. Verapamil
4. Nitroprusside
5. Acetylsalicylic acid (ASA)
6. Ticlopidine and clopidogrel
7. Unfractionated heparin (UFH)
8. Low-molecular-weight heparins (LMWHs)
9. Glycoprotein (GP) IIb/IIIa inhibitors
10. Direct thrombin inhibitors

Adjunctive Devices for PCI

1. Intracoronary brachytherapy for in-stent restenosis
2. Cutting balloon
3. Rotablation
4. Directional coronary atherectomy
5. Embolic protection devices
6. Adjunctive diagnostic technology

Drug-Eluting Stents (DES)

1. Cypher stent (Sirolimus)
2. Taxus stent (Paclitaxel)

• Rates of procedural complications including death, myocardial infarction, stroke, and need for re-intervention
• Survival and event-free survival rates
• Success rates of percutaneous coronary intervention (PCI) as defined by procedural and clinical criteria (i.e., relief of signs and symptoms, rate of re-stenosis)

Searches of Electronic Databases

A literature review was performed using Medline (PubMed) for peer-reviewed published literature. The use of abstracts was avoided. According to the European Society of Cardiology (ESC) recommendations for task force creation and report production, clinical trials presented at a major cardiology meeting were included for decision-making on the condition that the authors provided a draft of the final document to be submitted for publication.

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Levels of Evidence

1. Data derived from multiple randomized clinical trials or meta-analyses
2. Data derived from a single randomized clinical trial or large non-randomized studies
3. Consensus of opinion of the experts and/or small studies, retrospective studies, registries

Review of Published Meta-Analyses
Systematic Review with Evidence Tables

Not stated

Expert Consensus

Consensus could be achieved for all recommendations on the basis of evidence. To verify the applicability of the recommendations to a specific area, the expert panel emphasized the importance of the primary endpoint for the randomized trials, giving high priority to the importance of significantly improving patients' outcome as the primary endpoint investigated in an adequately powered sample size.

Classes of Recommendations

Class I: Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective

Class II: Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment

Class IIa: Weight of evidence/opinion is in favour of usefulness/efficacy.

Class IIb: Usefulness/efficacy is less well established by evidence/opinion.

The guideline developers reviewed published cost analyses.

Peer Review

Not stated

The levels of evidence (A-C) and classes of recommendations (I, II, IIa, and IIb) are defined at the end of the "Major Recommendations" field.

Indications for Percutaneous Coronary Interventions (PCI)

Indications for PCI in Stable Coronary Artery Disease (CAD)

Recommendations for PCI indications in stable CAD

Assuming that the lesions considered most significant are technically suited for dilation and stenting, the levels of recommendation refer to the use of stainless steel stents.

^a The benefit was limited to symptom improvement and exercise capacity.

^b The Asymptomatic Cardiac Ischemia Pilot (ACIP) study is not a pure trial of PCI vs. medical treatment as half of the revascularization patients were treated with bypass graft surgery. Drug-eluting stents are discussed subsequently.

Summary

PCI can be considered a valuable initial mode of revascularization in all patients with stable CAD and objective large ischaemia in the presence of almost every lesion subset, with only one exception: CTO that cannot be crossed. In early studies, there was a small survival advantage with coronary artery bypass graft (CABG) surgery compared with PCI without stenting. The addition of stents and newer adjunctive medications improved the outcome for PCI. The decision to recommend PCI or CABG surgery will be guided by technical improvements in cardiology or surgery, local expertise, and patients' preference. However, until proved otherwise, PCI should be used only with reservation in diabetics with multi-vessel disease and in patients with unprotected LM stenosis. The use of drug-eluting stents might change this situation.

Indications for PCI in Acute Coronary Syndromes (ACSs) without ST-Segment Elevation

Characteristics of patients with NSTE-ACS at high acute, thrombotic risk for rapid progression to myocardial infarction or death that should undergo coronary angiography within 48 hours:

1. Recurrent resting pain
2. Dynamic ST-segment changes: ST- segment depression >0.1 mV or transient (<30 min) ST-segment elevation >0.1/ mV
3. Elevated Troponin-I, Troponin-T, or CK-MB levels
4. Haemodynamic instability within the observation period
5. Major arrhythmias (ventricular tachycardia, ventricular fibrillation)
6. Early post-infarction unstable angina
7. Diabetes mellitus

Recommendations of PCI indications in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) (unstable angina [UA] or non ST-elevation myocardial infarction [NSTEMI])

Summary

Patients presenting with NSTE-ACS (UA or NSTEMI) have to be first stratified for their risk of acute thrombotic complications. A clear benefit from early angiography (<48h) and, when needed, PCI or CABG surgery has been reported only in the high-risk groups. Deferral of intervention does not improve the outcome. Routine stenting is recommended on the basis of the predictability of the result and its immediate safety.

Indications for PCI in ACS with ST-Segment Elevation (STE-ACS)

Recommendations for PCI in STE-ACS (STEMI)

Summary

Primary PCI should be the treatment of choice in patients presenting with STEMI in a hospital with PCI facility and an experienced team. Patients with contraindications to thrombolysis should be immediately transferred for primary PCI, because this might be their only chance for quickly opening the coronary artery. In cardiogenic shock, emergency PCI for complete revascularization may be life-saving and should be considered at an early stage. Compared with thrombolysis, randomized trials that transferred the patients for primary PCI to a "heart attack centre" observed a better clinical outcome, despite transport times leading to a significantly longer delay between randomization and start of the treatment. The superiority of primary PCI over thrombolysis seems to be especially clinically relevant for the time interval between 3 and 12 hours after onset of chest pain or other symptoms on the basis of its superior preservation of myocardium. Furthermore, with increasing time to presentation, major adverse cardiac event (MACE) rates increase after thrombolysis, but appear to remain relatively stable after primary PCI.

Within the first 3 hours after onset of chest pain or other symptoms, both reperfusion strategies seem equally effective in reducing infarct size and mortality. Therefore, thrombolysis is still a viable alternative to primary PCI, if it can be delivered within 3 hours after onset of chest pain or other symptoms. Primary PCI compared with thrombolysis significantly reduced stroke. Overall, we prefer primary PCI over thrombolysis in the first 3 hours of chest pain to prevent stoke and, in patients presenting 3-12 hours after the onset of chest pain, to salvage myocardium and also prevent stroke. At the moment, there is no evidence to recommend facilitated PCI.

Rescue PCI is recommended if thrombolysis failed within 45 to 60 minutes after starting the administration. After successful thrombolysis, the use of routine coronary angiography within 24 hours and PCI, if applicable, is recommended even in asymptomatic patients without demonstrable ischaemia to improve outcomes. If a PCI centre is not available within 24 hours, patients who have received successful thrombolysis with evidence of spontaneous or inducible ischaemia before discharge should be referred to coronary angiography and revascularized accordingly--independent of maximal medical therapy.

Adjunctive Medications for PCI

A routine pre-treatment with an intracoronary bolus of nitroglycerin (NTG) is recommended to unmask vasospasm, to assess the true vessel size, and to reduce the risk of vasospastic reactions during the procedure (Recommendation for NTG: I C). The bolus may be repeated during and at the end of the procedure, depending on the blood pressure. In the rare case of spasm resistant to NTG, verapamil is a useful alternative.

In the setting of "no/slow reflow" (see section 4.5, "Embolic protection devices," in the original guideline document), many reports investigated the intracoronary application of verapamil and adenosine in various dosages. The direct nitric oxide donor nitroprusside (NPN) seems also to be effective and safe treatment of reduced blood flow or no-reflow associated with PCI. In addition, an intra-aortic balloon pump (IABP) might be helpful. The combination of adenosine and nitroprusside provided an improvement in coronary flow that was better than the improvement with intracoronary adenosine alone. (Recommendations for adenosine, verapamil, and NPN for no/slow reflow: IIa C).

Acetylsalicylic Acid (ASA)

ASA in Stable CAD

ASA continues to play an important role in reducing ischaemic complications related to PCI. If patients are not chronically pre-treated or when there is doubt about medication compliance, a loading dose of 500 mg orally should be given more than 3 hours prior or at least 300 mg intravenously directly prior to the procedure. Only in patients with known allergy against ASA should it be omitted. As pointed out in the European Society of Cardiology consensus document, for chronic use, there is no need for doses higher than 100 mg daily. (Recommendation for ASA in PCI for stable CAD: I B).

ASA in NSTE-ACS

ASA is universally recommended as standard therapy in NSTE-ACS with and without PCI. (Recommendation for ASA in PCI for NSTE-ACS: I C).

ASA in STE-ACS (STEMI)

Despite the limitations and side effects of ASA, it should be given to all patients with STEMI (if clinically justifiable) as soon as possible after the diagnosis is established. (Recommendation for ASA in PCI for STEMI: I B).

Ticlopidine and Clopidogrel

Ticlopidine and clopidogrel are potent antiplatelet compounds. According to three randomized, controlled studies and several registries and meta-analyses, clopidogrel seems to be at least as effective as ticlopidine. Compared with ticlopidine, clopidogrel has fewer side-effects and is better tolerated.

Recommendations for clopidogrel as adjunctive medication for PCI

Summary

The "double" antiplatelet therapy with ASA and clopidogrel is standard for the pre-treatment of patients with stable CAD undergoing PCI--with or without planned stent implantation. After implantation of a bare metal stent, clopidogrel must be continued for 3 to 4 weeks and ASA lifelong. In patients presenting with NSTE-ACS, ASA and, if clinically justifiable, immediate administration of clopidogrel, is the basic standard antiplatelet regimen. After the acute phase, the continuation of 100 mg/day ASA + clopidogrel 75 mg/day over 9 to 12 months is beneficial. ASA should be given intravenously to all patients with STEMI as soon as possible after the diagnosis is established, if clinically justifiable. With the concept of primary PCI and primary-stenting in STEMI, clopidogrel will be additionally administered in these patients. After brachytherapy, clopidogrel should be administered in addition to ASA for 12 months and after drug-eluting stents for 6 to 12 months to avoid late vessel thrombosis.

Unfractionated Heparin (UFH)

UFH for PCI in stable CAD

UFH is given as an intravenous bolus either under activated clotting time (ACT) guidance or in a weight-adjusted manner. Because of marked variability in UFH bio-availability, ACT- guided dosing is advocated, especially for prolonged procedures when additional bolus (-es) may be required. The therapeutic response to UFH in general is difficult to predict. There is evidence that its benefit is linked to an effective dose, although low doses (5000 IU or lower) have been used in routine procedures. Continued heparinization after completion of the procedure, either preceding or following arterial sheath removal is not recommended.

UFH for PCI in NSTE-ACS

Adding UFH as a standard regimen is usually recommended on the basis of a meta-analysis of six smaller randomized trials showing a 7.9% rate of death/myocardial infarction in patients with unstable angina treated with ASA plus heparin compared with 10.3% in those treated with ASA alone. Discontinuation of UFH in patients with unstable angina carries the inherent risk of a rebound effect.

UFH for PCI in STE-ACS (STEMI)

UFH is the standard therapy in patients with STEMI especially for those undergoing primary PCI. (Recommendation for unfractionated heparin for all PCI procedures: I C)

Low-Molecular Weight Heparins (LMWHs)

LMWHs for PCI in stable CAD

The data on LMWHs as sole anticoagulant during PCI in stable CAD patients are limited. To be on the safe side, it is suggested that UFH should be added in patients arriving on pre-treatment with LMWHs, according to the interval of the last LMWH dose.

LMWHs for PCI in NSTE-ACS

Switching from UFH to LMWH and vice versa should generally be avoided. If LMWH has been administered prior to PCI, the administration of additional anticoagulant therapy depends on the timing of the last dose of LMWH.

Combining the results of several studies, UFH should be preferred in high-risk NSTE-ACS patients with planned invasive strategy. Furthermore, although enoxaparin can be administered before PCI in NSTE-ACS, the Task Force recommends UFH because of its easier reversibility by the administration of protamine. There is no firm evidence that enoxaparin can be used safely in the cathlab, but this possibility is currently being explored.

If an invasive strategy is, for some reason, not applicable in a high-risk NSTE-ACS patient, enoxaparin could be preferred for reducing ischaemic complications. (Recommendation for LMWHs as a replacement for UFH in high-risk NSTE-ACS, if invasive strategy is not applicable: I C)

LMWHs for PCI in STE-ACS (STEMI)

Unless more data from pivotal studies are provided, there is no evidence to support the preference of LMWHs over UFH for PCI in STEMI.

Summary

UFH is given as an intravenous bolus under activated clotting time (ACT) guidance. Because of their pharmacologic advantages, LMWHs are considered to be more predictable anticoagulants, not requiring laboratory monitoring. However, the data on LMWHs as sole anticoagulant during PCI in stable CAD patients is limited. UFH is to be preferred in high-risk NSTE-ACS patients with planned invasive strategy and in lower risk patients with planned conservative strategy. If in high-risk NSTE-ACS patients, an invasive strategy is not applicable for some reason, enoxaparin may be preferred, taking into account an increase in minor bleeding. In patients with STEMI undergoing primary PCI, UFH is the standard therapy.

Glycoprotein IIb/IIIa Inhibitors

See table below under "Direct Thrombin Inhibitors."

Direct Thrombin Inhibitors

The table below contains recommendations pertaining to both glycoprotein inhibitors and direct thrombin inhibitors.

Recommendations for glycoprotein (GP) IIb/IIIa inhibitors and bivalirudin as adjunctive medications for PCI

Summary

Given the overall low risk of PCI in stable CAD patients, the potential of GP IIb/IIIa inhibitors to increase the risk of bleeding complications, and the considerable cost of their use, they are not a part of standard periprocedural medication. The use of GP IIb/IIIa inhibitors for PCI in stable angina should be considered on an elective basis: whenever there is a higher than average risk of acute thrombotic complications in stable CAD (complex interventions, unstable lesions, as bail-out medication in case of threatening/actual vessel closure, visible thrombus, or no/slow-reflow phenomenon), GP IIb/IIIa inhibitors are helpful.

In NSTE-ACS, GP IIb/IIIa inhibitors should be added only in high-risk patients, in whom an invasive strategy is planned. For "upstream" management (i.e., initiating therapy when the patient first presents to the hospital and catheterization is not planned or available within 2.5 hours), tirofiban and eptifibatide show benefit. If cardiac catheterization is likely to be performed within 2.5 hours, GP IIb/IIIa inhibitors could possibly be postponed and abciximab or eptifibatide initiated in the catheterization laboratory. If, for some reason, the delay between diagnostic catheterization and planned PCI is up to 24 hours, abciximab can also be administered.

In patients with STEMI, the GP IIb/IIIa inhibitors tirofiban and eptifibatide are less well investigated. In STEMI, stenting plus abciximab seems to be a more evidence-based reperfusion strategy. Bivalirudin is suggested today as a replacement for UFH (or LMWHs) because of significantly less bleeding compared with UFH alone or UFH + GP IIb/IIIa inhibitors. Bivalirudin is unanimously recommended for PCI as a replacement for UFH (and LMWHs) in patients with HIT.

Adjunctive Devices for PCI

Recommendations for adjunctive PCI devices

Summary

Intracoronary brachytherapy proved to be the only evidence-based non-surgical treatment of in-stent restenosis. To avoid late vessel thrombosis, a prolonged intake of clopidogrel for 1 year after radiation therapy is necessary.

Rotablation is recommended for fibrotic or heavily calcified lesions that can be wired but not crossed by a balloon or adequately dilated before planned stenting. One must know how to manage the complications inherent to rotablation.

PCI of saphenous vein grafts (SVGs) or primary PCI in ACS with a high thrombotic load is at elevated risk for coronary embolization. Two distal protection devices (GuardWire and FilterWire EX) have proved their safety and efficacy as an adjunctive device for PCI of SVG lesions.

Whether balloon occlusion and aspiration systems of filter-based catheters will be preferred in other clinical settings such as primary PCI for STEMI will require more randomized trials with a clinical primary endpoint. At present, no definite recommendations can be given regarding the use of embolic protection devices in the setting of STEMI.

Adjunctive Diagnostic Technology

Refer to the original guideline document for the discussion on adjunctive diagnostic technology including intravascular ultrasound (IVUS) and fractional flow reserve.

Drug-Eluting Stents (DES)

Indications for DES

Recommendations for the use of DES in de novo lesions of native coronary arteries

There are only three positive controlled, randomized, adequately powered trials with a primary clinical endpoint at an appropriate time interval. Main clinical inclusions criteria for SIRIUS, TAXUS-IV, and TAXUS-VI were similar: stable or unstable angina or documented ischaemia. The stenoses had to be in native vessels >50 <100%. In SIRIUS, reference diameter and lesion length for inclusion were 2.5 to 3.5 mm and 15 to 30 mm, respectively. The reference diameter in TAXUS-IV and TAXUS-VI was 2.5 to 3.75 mm. In TAXUS-IV, the lesion length was 10 to 28 mm and in TAXUS-VI 18 to 40 mm. The main common exclusion criteria were acute MI or status post MI with elevated creatine kinase (CK)/creatine kinase-MB (CK-MB), bifurcational or ostial lesions, unprotected left main, visible thrombus, severe tortuosity, and/or calcification.

Summary

Only two DES have shown significantly positively effects in prospective, randomized studies with clinical primary endpoints at an appropriate time: the Cypher stent (Sirolimus) and the Taxus stent (Paclitaxel). Evidence-based recommendations for the use of DES must focus on the enrollment criteria of SIRIUS, TAXUS-IV, and TAXUS-VI. In these patients, target vessel revascularization (TVR) rates were single-digit numbers. Subgroup analyses regarding smaller vessels and patients with diabetes are encouraging. Although registry data for in-stent restenosis as well as for other lesions with high risk for in-stent restenosis (bifurcational or ostial lesions, chronic total occlusions, multi-vessel disease, bypass stenosis, and unprotected left main stenoses) is promising, randomized trials must be conducted for achieving higher levels of evidence in these special subsets of patients. At present, we consider the prolonged (at least 6 months) administration of clopidogrel (in addition to ASA) as mandatory to avoid late stent thrombosis. Therefore, in patients undergoing or who soon will be undergoing urgent major extracardiac surgery, DES should not be implanted. In these patients, bare stents are probably the safer choice. Physicians and patients must be made aware that clopidogrel should not be discontinued too early, even for minor procedures like dental care.

Definitions:

Levels of Evidence

1. Data derived from multiple randomized clinical trials or meta-analyses
2. Data derived from a single randomized clinical trial or large non-randomized studies
3. Consensus of opinion of the experts and/or small studies, retrospective studies, registries

Classes of Recommendations

Class I: Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective

Class II: Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment

Class IIa: Weight of evidence/opinion is in favour of usefulness/efficacy.

Class IIb: Usefulness/efficacy is less well established by evidence/opinion.

Algorithms are provided in the original guideline document for the management of:

• Patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS)
• Patients with ST-segment elevation myocardial infarction (STEMI) who present within 12 hours after the onset of symptoms

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations" field).

Appropriate use of percutaneous coronary intervention (PCI) in the treatment of patients with coronary artery disease (CAD)

• Ischaemic complications of percutaneous coronary intervention (PCI)
• Adverse effects of adjunctive medications for PCI (i.e., bleeding associated with glycoprotein IIb/IIIa inhibitors, unfractionated heparin, low-molecular-weight heparins, and bivalirudin)

Absolute contraindications to thrombolysis are the following conditions: aortic dissection, status post haemorrhagic stroke, recent major trauma/surgery, gastrointestinal (GI) bleeding within the last month or a known bleeding disorder.

An implementation strategy was not provided.

Living with Illness

Effectiveness
Timeliness

Not applicable: The guideline was not adapted from another source.

2005 Apr

European Society of Cardiology - Medical Specialty Society

European Society of Cardiology

Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology

Task Force Members: Sigmund Silber (Chairperson) (Germany); Per Albertsson (Sweden); Francisco F. Avilés (Spain); Paolo G. Camici (UK); Antonio Colombo (Italy); Christian Hamm (Germany); Erik Jørgensen (Denmark); Jean Marco (France); Jan-Erik Nordrehaug (Norway); Witold Ruzyllo (Poland); Philip Urban (Switerland); Gregg W. Stone (USA); William Wijns (Belgium)

European Society of Cardiology (ESC) Committee for Practice Guidelines Members: Silvia G. Priori (Chairperson) (Italy); Maria Angeles Alonso Garcia (Spain); Jean-Jacques Blanc (France); Andrzej Budaj (Poland); Martin Cowie (UK); Veronica Dean (France); Jaap Deckers (The Netherlands); Enrique Fernandez Burgos (Spain); John Lekakis (Greece); Bertil Lindahl (Sweden); Gianfranco Mazzotta (Italy); Keith McGregor (France); João Morais (Portugal); Ali Oto (Turkey); Otto A. Smiseth (Norway)

The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the European Society of Cardiology (ESC).

This is the current release of the guideline.

None available

This NGC summary was completed by ECRI on September 26, 2005. This summary was updated by ECRI Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection. This summary was updated by ECRI Institute on July 12, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Troponin-1 Immunoassay. This summary was updated by ECRI Institute on March 14, 2008 following the updated FDA advisory on heparin sodium injection. This summary was updated by ECRI Institute on December 26, 2008 following the FDA advisory on Innohep (tinzaparin).

This summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.