2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention
A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, Writing on Behalf of the 2005 Writing Committee
- 1. Introduction
- 2. Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
- 3. Facilitated PCI
- 4. Rescue PCI
- 5. PCI After Fibrinolysis or for Patients Not Undergoing Primary Reperfusion
- 6. Ancillary Therapy for Patients Undergoing PCI for STEMI
- 7. Antiplatelet Therapy
- 8. Bare-Metal and Drug-Eluting Stents
- 9. Secondary Prevention
- Figures & Tables
- Supplemental Materials
- Info & Metrics
1.1. Evidence Review…264
1.2. Organization of Committee and Relationships With Industry…264
1.3. Review and Approval…264
2. Patients With Unstable Angina/ Non–ST-Elevation Myocardial Infarction…264
2.1.1. Comparison of Early Invasive and Initial Conservative Strategies for UA/NSTEMI…269
2.1.2. Selection for Coronary Angiography…271
2.1.3. Chronic Kidney Disease…272
3. Facilitated PCI…273
4. Rescue PCI…275
5. PCI After Fibrinolysis or for Patients Not Undergoing Primary Reperfusion…277
6. Ancillary Therapy for Patients Undergoing PCI for STEMI…278
7. Antiplatelet Therapy…278
8. Bare-Metal and Drug-Eluting Stents…281
8.1. Selection of a Bare-Metal or Drug-Eluting Stent…281
9. Secondary Prevention…283
A primary challenge in the development of clinical practice guidelines is keeping pace with the stream of new data upon which recommendations are based. In an effort to respond more quickly to new evidence, the American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines has created a new “focused update” process to revise the existing guideline recommendations that are affected by evolving data or opinion. Before the initiation of this focused approach, periodic updates and revisions of existing guidelines required up to 3 years to complete. Now, however, new evidence will be reviewed in an ongoing fashion to more efficiently respond to important science and treatment trends that could have a major impact on patient outcomes and quality of care. Evidence will be reviewed at least twice a year, and updates will be initiated on an as needed basis as quickly as possible while maintaining the rigorous methodology that the ACC and AHA have developed during their more than 20 years of partnership.
These updated guideline recommendations reflect a consensus of expert opinion following a thorough review primarily of late-breaking clinical trials identified through a broad-based vetting process as important to the relevant patient population and of other new data deemed to have an impact on patient care (see Section 1.1 for details regarding this focused update). It is important to note that this focused update is not intended to represent an update based on a full literature review from the date of the previous guideline publication. Specific criteria/considerations for inclusion of new data include:
Publication in a peer-reviewed journal
Large, randomized, placebo-controlled trial(s)
Nonrandomized data deemed important on the basis of results that impact current safety and efficacy assumptions
Strengths/weakness of research methodology and findings
Likelihood of additional studies influencing current findings
Impact on current performance measure(s) and/or likelihood of the need to develop new performance measure(s)
Requests and requirements for review and update from the practice community, key stakeholders, regulatory agencies, and other sources free of relationships with industry or other potential bias
Number of previous trials showing consistent results
Need for consistency with other new guidelines or guideline revisions
In analyzing the data and developing updated recommendations and supporting text, the focused update writing group used evidence-based methodologies developed by the ACC/AHA Task Force on Practice Guidelines, which are described elsewhere.1,2
The schema for class of recommendation and level of evidence is summarized in Table 1, which also illustrates how the grading system provides estimates of the size of the treatment effect and the certainty of the treatment effect. Note that a recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in guidelines do not lend themselves to clinical trials. Although randomized trials may not be available, there may be a very clear clinical consensus that a particular test or therapy is useful and effective. Both the class of recommendation and level of evidence listed in the focused updates are based on consideration of the evidence reviewed in previous iterations of the guidelines as well as the focused update. Of note, the implications of older studies that have informed recommendations but have not been repeated in contemporary settings are carefully considered.
The ACC/AHA practice guidelines address patient populations (and health care providers) residing in North America. As such, drugs that are not currently available in North America are discussed in the text without a specific class of recommendation. For studies performed in large numbers of subjects outside of North America, each writing committee reviews the potential impact of different practice patterns and patient populations on the treatment effect and on the relevance to the ACC/AHA target population to determine whether the findings should form the basis of a specific recommendation.
The ACC/AHA practice guidelines are intended to assist health care providers in clinical decision making by describing a range of generally acceptable approaches for the diagnosis, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. The ultimate judgment regarding care of a particular patient must be made by the health care provider and patient in light of all the circumstances presented by that patient. Thus, there are circumstances in which deviations from these guidelines may be appropriate. Clinical decision making should consider the quality and availability of expertise in the area where care is provided. These guidelines may be used as the basis for regulatory or payer decisions, but the ultimate goal is quality of care and serving the patient’s best interests.
Prescribed courses of treatment in accordance with these recommendations are only effective if they are followed by the patient. Because lack of patient adherence may adversely affect treatment outcomes, health care providers should make every effort to engage the patient in active participation with prescribed treatment.
The ACC/AHA Task Force on Practice Guidelines makes every effort to avoid any actual, potential, or perceived conflict of interest arising from industry relationships or personal interests of a writing committee member. All writing committee members and peer reviewers were required to provide disclosure statements of all such relationships pertaining to the trials and other evidence under consideration (see Appendixes 1 and 2). Final recommendations were balloted to all writing committee members. Writing committee members with significant (greater than $10 000) relevant relationships with industry (RWI) were required to recuse themselves from voting on that recommendation. Writing committee members who did not participate are not listed as authors of this focused update.
With the exception of the recommendations presented in this statement, the full guidelines remain current. Only the recommendations from the affected section(s) of the full guidelines are included in this focused update. For easy reference, all recommendations from any section of guidelines impacted by a change are presented with a notation as to whether they remain current, are new, or have been modified. When evidence impacts recommendations in more than 1 set of guidelines, those guidelines are updated concurrently.
The recommendations in this focused update will be considered current until they are superseded by another focused update or the full-text guidelines are revised. This focused update is published in the January 15, 2008, issue of the Journal of the American College of Cardiology, the January 15, 2008, issue of Circulation, and e-published in Catheterization and Cardiovascular Interventions as an update to the full-text guidelines and is posted on the ACC (www.acc.org), AHA (my.americanheart.org), and Society for Angiography and Interventions (SCAI) (www.scai.org) Web sites. Copies of the focused update are available from all organizations.
Sidney C. Smith, Jr., MD, FACC, FAHA
Chair, ACC/AHA Task Force on Practice Guidelines
Alice K. Jacobs, MD, FACC, FAHA
Vice-Chair, ACC/AHA Task Force on Practice Guidelines
1.1. Evidence Review
Selected late-breaking clinical trials presented at the 2005 and 2006 annual scientific meetings of the ACC, AHA, and European Society of Cardiology, as well as selected other data, were reviewed by the standing guideline writing committee along with the parent Task Force and other experts to identify those trials and other key data that might impact guideline recommendations. On the basis of the criteria/considerations noted above, recent trial data and other clinical information were considered important enough to prompt a focused update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention.3–13
To provide clinicians with a comprehensive set of data, whenever possible, the exact event rates in various treatment arms of clinical trials are presented to permit calculation of the absolute risk difference (ARD) and number needed to treat (NNT) or harm (NNH); the relative treatment effects are described either as odds ratio (OR), relative risk (RR), or hazard ratio (HR), depending on the format in the original publication.
Consult the full-text version or executive summary of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention for policy on clinical areas not covered by the focused update.13a Individual recommendations updated in this focused update will be incorporated into future revisions and/or updates of the full-text guidelines.
1.2. Organization of Committee and Relationships With Industry
For this focused update, all members of the 2005 PCI writing committee were invited to participate; those who agreed (referred to as the 2007 focused update writing group) were required to disclose all RWI relevant to the data under consideration.2 Focused update writing group members who had no significant relevant RWI wrote the first draft of the focused update; the draft was then reviewed and revised by the full writing group. Each recommendation required a confidential vote by the writing group members before external review of the document. Any writing committee member with a significant (greater than $10 000) RWI relevant to the recommendation was recused from voting on that recommendation.
1.3. Review and Approval
This document was reviewed by 2 outside reviewers nominated by each cosponsoring organization (ACC, AHA, and SCAI) and 24 individual content reviewers. All reviewer RWI information was collected and distributed to the writing committee and is published in this document (see Appendix 2 for details).
This document was approved for publication by the governing bodies of the American College of Cardiology Foundation, AHA, and SCAI.
2. Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
This 2007 PCI Focused Update section regarding patients with unstable angina (UA)/non–ST-elevation myocardial infarction (NSTEMI) is based on recommendations from the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction,14 which emphasize the importance of assessing risk of cardiovascular events as a guide to therapeutic decision making and the need for interventional therapy (see Table 2⇓⇓).
A number of risk-assessment tools have been developed to assist in assessing risk of death and ischemic events in patients with UA/NSTEMI, thereby providing a basis for therapeutic decision making. It should be recognized that the predictive ability of these commonly used risk assessment scores for risk of nonfatal coronary heart disease (CHD) is only moderate.
The Thrombolysis in Myocardial Infarction (TIMI) risk score15 is a simple tool composed of 7 (1-point) risk indicators rated on presentation (Table 4). The composite end points (all-cause mortality, new or recurrent myocardial infarction [MI], or severe recurrent ischemia prompting urgent revascularization within 14 days) increase as the TIMI risk score increases. The TIMI risk score has been validated internally within the TIMI IIB trial and 2 separate cohorts of patients from the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non–Q-Wave Myocardial Infarction) trial.16 The model remained a significant predictor of events and appeared relatively insensitive to missing information, such as knowledge of previously documented coronary stenosis of 50% or greater. The model’s predictive ability remained intact, with a cutoff of 65 years of age. The TIMI risk score was recently studied in an unselected emergency department population with chest pain syndrome; its performance was similar to that in the acute coronary syndrome (ACS) population from which it was derived and validated.17 The TIMI risk calculator is available at www.timi.org. The TIMI risk index, a modification of the TIMI risk score that uses the variables age, systolic blood pressure, and heart rate, has not only been shown to predict short-term mortality in ST-elevation myocardial infarction (STEMI) but also has been useful in prediction of 30-day and 1-year mortality rates across the spectrum of patients with ACS, including UA/NSTEMI.18
The PURSUIT (Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial risk model,19 based on patients enrolled in the PURSUIT trial, is another useful tool to guide the clinical decision-making process when the patient is admitted to the hospital. In the PURSUIT risk model, critical clinical features associated with an increased 30-day incidence of death and the composite of death or myocardial (re)infarction were (in order of strength) age, heart rate, systolic blood pressure, ST-segment depression, signs of heart failure (HF), and cardiac enzymes.19
The GRACE (Global Registry of Acute Coronary Events) study risk model, which predicts in-hospital mortality (and death or MI), can be useful to clinicians to guide treatment type and intensity.20,21 The GRACE risk tool was developed on the basis of 11 389 patients in GRACE and validated in subsequent GRACE and GUSTO (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) IIb cohorts and predicts in-hospital death in patients with STEMI, NSTEMI, or UA (C statistic=0.83). The 8 variables used in the GRACE risk model are older age (OR 1.7 per 10 years), Killip class (OR 2.0 per class), systolic blood pressure (OR 1.4 per 20 mm Hg decrease), ST-segment deviation (OR 2.4), cardiac arrest during presentation (OR 4.3), serum creatinine level (OR 1.2 per 1 mg per dL increase), positive initial cardiac markers (OR 1.6), and heart rate (OR 1.3 per 30-bpm increase). The sum of scores is applied to a reference nonogram to determine the corresponding all-cause mortality from hospital discharge to 6 months. The GRACE clinical application tool can be downloaded to a handheld PDA (personal digital assistant) to be used at the bedside and is available at www.outcomes-umassmed.org/grace (Figure 1).21 An analysis comparing the 3 risk scores (TIMI, GRACE, and PURSUIT) concluded that all 3 demonstrated good predictive accuracy for death and MI at 1 year, thus identifying patients who might be likely to benefit from aggressive therapy, including early myocardial revascularization.22
The electrocardiogram (ECG) provides unique and important diagnostic and prognostic information (see also Section 2.1 below). Accordingly, ECG changes have been incorporated into quantitative decision aids for the triage of patients who present with chest discomfort.23 Although ST elevation carries the highest early risk of death, ST depression on the presenting ECG portends the highest risk of death at 6 months, with the degree of ST-segment depression showing a strong relationship to outcome.24
The recommendations in the ACC/AHA 2007 UA/NSTEMI Guidelines14 recognize recent data from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, which showed that in patients with ACS who were undergoing invasive treatment, bivalirudin alone was associated with rates of ischemia similar to those treated with glycoprotein (GP) IIb/IIIa inhibitors plus heparin and significantly less bleeding.25
The ACC/AHA 2007 UA/NSTEMI Guidelines cite a progressively greater benefit from newer, more aggressive therapies such as low-molecular-weight heparin (LMWH),16,26 platelet GP IIb/IIIa inhibition,27 and an invasive strategy28 with increasing risk score.
The ECG lies at the center of the decision pathway for the evaluation and management of patients with acute ischemic discomfort (Table 5). The diagnosis of MI is confirmed with serial cardiac biomarkers in more than 90% of patients who present with ST-segment elevation greater than or equal to 1 mm (0.1 mV) in at least 2 contiguous leads, and such patients should be considered candidates for acute reperfusion therapy. Patients who present with ST-segment depression are initially considered to have either UA or NSTEMI; the distinction between the 2 diagnoses is ultimately based on the detection of markers of myocardial necrosis in the blood.29–31
Up to 25% of patients with NSTEMI and elevated CK-MB go on to develop Q-wave MI during their hospital stay, whereas the remaining 75% have non–Q-wave MI. Acute fibrinolytic therapy is contraindicated for ACS patients without ST-segment elevation, except for those with electrocardiographic true posterior MI manifested as ST-segment depression in 2 contiguous anterior precordial leads and/or isolated ST-segment elevation in posterior chest lead.32–34 Inverted T waves may also indicate UA/NSTEMI. In patients suspected of having ACS on clinical grounds, marked (greater than or equal to 2 mm [0.2 mV]) symmetrical precordial T-wave inversion strongly suggests acute ischemia, particularly that associated with a critical stenosis of the left anterior descending coronary artery (LAD).35 Patients with this ECG finding often exhibit hypokinesis of the anterior wall and are at high risk if given medical treatment alone.36 Revascularization will often reverse both the T-wave inversion and wall-motion disorder.37 Nonspecific ST-segment and T-wave changes, usually defined as ST-segment deviation less than 0.5 mm (0.05 mV) or T-wave inversion less than or equal to 2 mm (0.2 mV), are less diagnostically helpful than the foregoing findings. Established Q waves greater than or equal to 0.04 second are also less helpful in the diagnosis of UA, although by suggesting prior MI, they do indicate a high likelihood of significant coronary artery disease (CAD). Isolated Q waves in lead III may be a normal finding, especially in the absence of repolarization abnormalities in any of the inferior leads. A completely normal ECG in a patient with chest pain does not exclude the possibility of ACS, because 1% to 6% of such patients eventually are proven to have had an MI (by definition, NSTEMI), and at least 4% will be found to have UA.38–40
In addition to the presence or absence of ST-segment deviation or T-wave inversion patterns noted earlier, there is evidence that the magnitude of the ECG abnormality provides important prognostic information. Thus, Lloyd-Jones et al.41 reported that the diagnosis of acute non–Q-wave MI was 3 to 4 times more likely in patients with ischemic discomfort who had at least 3 ECG leads that showed ST-segment depression and maximal ST depression of greater than or equal to 0.2 mV. Investigators from the TIMI III Registry42 reported that the 1-year incidence of death or new MI in patients with at least 0.5 mm (0.05 mV) of ST-segment deviation was 16.3% compared with 6.8% for patients with isolated T-wave changes and 8.2% for patients with no ECG changes.
Cardiogenic shock can occur in the setting of both STEMI and NSTEMI, and there is high mortality and morbidity in each. The SHOCK (SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK) study43 found that approximately 20% of all cardiogenic shock complicating MI was associated with NSTEMI. The GUSTO-II44 and PURSUIT45 trials found that cardiogenic shock occurs in up to 5% of patients with NSTEMI and that mortality rates are greater than 60%. Thus, hypotension and evidence of organ hypoperfusion can occur and constitute a medical emergency in NSTEMI.
2.1.1. Comparison of Early Invasive and Initial Conservative Strategies for UA/NSTEMI
Prior meta-analyses concluded that routine invasive therapy (the “invasive” or “early” strategy triages patients to undergo an invasive diagnostic evaluation without first getting a noninvasive stress test or without failing medical treatment [i.e., an initial conservative diagnostic strategy or sometimes now known as the “selective invasive strategy”]14) is better than an initial conservative or selectively invasive approach (the “initial conservative strategy” [also referred to as “selective invasive management”] calls for proceeding with an invasive evaluation only for those patients who fail medical therapy [refractory angina or angina at rest or with minimal activity despite rigorous medical therapy] or in whom objective evidence of ischemia [dynamic ECG changes, high-risk stress test] is identified14). Mehta et al47 concluded that the routine invasive strategy resulted in an 18% relative reduction in death or MI, including a significant reduction in MI alone. The routine invasive arm was associated with higher in-hospital mortality (1.8% versus 1.1%), but this disadvantage was more than compensated for by a significant reduction in mortality between discharge and the end of follow-up (3.8% versus 4.9%). In those analyses, the invasive strategy was associated with less angina and fewer rehospitalizations than the conservative pathway. Patients undergoing routine invasive treatment also had improved quality of life.
In contrast to these findings, other studies, most recently ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes), have favorably highlighted a strategy of selective invasive therapy.48 In ICTUS, 1200 high-risk ACS patients without ST-segment elevation were randomized to receive routine invasive versus selective invasive management and followed up for 1 year with respect to the combined incidence of death, MI, and ischemic rehospitalization. All patients were treated with optimal medical therapy that included aspirin, clopidogrel, LMWH, and lipid-lowering therapy; abciximab was given to those undergoing revascularization. At the end of 1 year, there was no significant difference in the composite end point between groups. This study suggests that a selective invasive strategy could be reasonable for ACS patients. A possible explanation for the lack of benefit of the invasive approach in this trial (and other trials)49 could be related to the relatively high rate of revascularization actually performed in patients treated in the selective invasive arm (47%), thereby reducing observed differences between treatment strategies,22 and to the lower event rate (lower-risk population) than in other studies. Results were unchanged during longer-term follow-up.50,51 Nevertheless, ICTUS required troponin positivity for entry. Thus, troponin alone might no longer be an adequate criterion for strategy selection, especially with increasingly sensitive troponin assays. The degree of troponin elevation and other high-risk clinical factors taken together should be considered in selecting a treatment strategy. The ICTUS trial was relatively underpowered for hard end points, and it used a controversial definition for post procedural MI (i.e., even minimal asymptomatic CK-MB elevation).48,50,51
Additionally, 1-year follow-up may be inadequate to fully realize the long-term impact and benefit of the routine invasive strategy. In the RITA-3 trial (Third Randomized Intervention Trial of Angina), 5-year but not 1-year event rates favored the early invasive arm (see Figure 2 and text below).52 In ICTUS, however, results were maintained during a 3-year follow-up.53
Thus, the 2007 UA/NSTEMI Guidelines14 recommend that in initially stabilized UA/NSTEMI patients, an initial conservative (selective invasive) strategy may be considered as an alternative treatment option. The writing committee also believes that additional comparative trials of the selective invasive with the routine initial invasive strategies are indicated, using aggressive contemporary medical therapies in both arms, including routine dual antiplatelet therapy (DAT) in medically treated patients as well as aggressive lipid lowering and other updated secondary prevention measures.
Nevertheless, a meta-analysis of contemporary randomized trials in NSTEMI, including ICTUS, currently support long-term mortality and morbidity benefits of an early invasive compared with an initial conservative strategy.54 Nonfatal MI at 2 years (7.6% vs. 9.1%, respectively; RR 0.83 [95% CI 0.72 to 0.96]; p = 0.012) and hospitalization (at 13 months; RR = 0.69 [95% CI 0.65 to 0.74]; p less than 0.0001) also were reduced by an early invasive strategy (Figure 3). A separate review of contemporary randomized trials in the stent era using the Cochrane Database arrived at similar conclusions.55 Details of selected contemporary trials of invasive versus conservative strategies may be found in the ACC/AHA 2007 UA/NSTEMI Guidelines.14
Thus, the FRISC-II (Fragmin and Fast Revascularisation during InStability in Coronary artery disease)56 and TACTICS (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy)-TIMI 1828 trials showed a benefit in patients assigned to invasive strategy. In contrast to earlier trials, a large majority of patients undergoing percutaneous coronary intervention (PCI) in these 2 trials received coronary stenting as opposed to balloon angioplasty alone. Also, there was a differential rate of thienopyridine use between the 2 arms; only stented patients were treated. In FRISC-II, the invasive strategy involved treatment with LMWH, aspirin, nitrates, and beta blockers for an average of 6 days in the hospital before coronary angiography, an approach that would be difficult to adopt in US hospitals. In TACTICS-TIMI 18, treatment included the GP IIb/IIIa antagonist tirofiban, which was administered for an average of 22 hours before coronary angiography. The routine use of the GP IIb/IIIa inhibitor in this trial may have eliminated the excess risk of early (within 7 days) MI in the invasive arm, a risk that was observed in FRISC-II and other trials in which there was no routine “upstream” use of a GP IIb/IIIa blocker. Therefore, an invasive strategy is associated with a better outcome in UA/NSTEMI patients at high risk as defined in Table 3 and as demonstrated in TACTICS-TIMI 18 when a GP IIb/IIIa inhibitor is used.28 Although the benefit of intravenous GP IIb/IIIa inhibitors is established for UA/NSTEMI patients undergoing PCI, the optimal time to start these drugs before the procedure has not been established. In the PURSUIT trial,45 in patients with UA/NSTEMI who were admitted to community hospitals, the administration of eptifibatide was associated with a reduced need for transfer to tertiary referral centers and improved outcomes.57
The RITA-3 trial52 compared early and conservative therapy in 1810 moderate-risk patients with ACS. Patients with positive cardiac biomarkers (CK-MB greater than 2 times the upper limit of normal at randomization) were excluded from randomization, as were those with new Q waves, MI within 1 month, PCI within 1 year, and any prior coronary artery bypass graft (CABG). The combined end point of death, nonfatal MI, and refractory angina was reduced from 14.5% to 9.6% by early invasive treatment. The benefit was driven primarily by a reduction in refractory angina. There was a late divergence of the curves, with reduced 5-year death and MI in the early invasive arm (Figure 2).
In the VINO trial (Value of first day angiography/ angioplasty In evolving Non-ST segment elevation myocardial infarction: Open multicenter randomized trial),58 131 patients with NSTEMI were randomized to cardiac catheterization on the day of admission versus conservative therapy. Despite the fact that 40% of the conservatively treated patients crossed over to revascularization by the 6-month follow-up, there was a significant reduction in death or reinfarction for patients assigned to early angiography and revascularization (6% versus 22%).
The ISAR-COOL (Intracoronary Stenting with Antithrombotic Regimen Cooling-off) trial59 randomized 410 intermediate- to high-risk patients to very early angiography and revascularization versus a delayed invasive strategy. All patients were treated with intensive medical therapy that included aspirin, heparin, clopidogrel (600-mg loading dose), and the intravenous GP IIb/IIIa receptor inhibitor tirofiban. In the very early arm, patients underwent cardiac catheterization at a mean time of 2.4 hours versus 86 hours in the delayed invasive arm. The very early invasive strategy was associated with significantly better outcome at 30 days, as measured by reduction in death and large MI (5.9% versus 11.6%). More importantly, the benefit seen was attributable to a reduction in events before cardiac catheterization, which raises the possibility that there is a hazard associated with a “cooling-down” period.
2.1.2. Selection for Coronary Angiography
In contrast to the noninvasive tests, coronary angiography provides detailed structural information to allow assessment of prognosis and provide direction for appropriate management. When combined with left ventricular (LV) angiography, it also allows an assessment of global and regional LV function. Indications for coronary angiography are interwoven with indications for possible therapeutic plans, such as PCI or CABG.
Coronary angiography is usually indicated in patients with UA/NSTEMI who either have recurrent symptoms or ischemia despite adequate medical therapy or are at high risk as categorized by clinical findings (HF, serious ventricular arrhythmias) or noninvasive test findings (significant LV dysfunction: ejection fraction less than 0.35, large anterior or multiple perfusion defects) (Tables 6, 7, and 8⇓⇓). Patients with UA/NSTEMI who have had previous PCI or CABG also should generally be considered for early coronary angiography unless prior coronary angiography data indicate that further revascularization is not likely to be possible. The placement of an intra-aortic balloon pump (IABP) may allow coronary angiography and revascularization in those with hemodynamic instability. Patients with suspected Prinzmetal’s variant angina also are candidates for coronary angiography.
In all cases, the general indications for coronary angiography and revascularization are tempered by individual patient characteristics and preferences. Patient and physician judgments regarding risks and benefits are particularly important for patients who might not be candidates for coronary revascularization, such as very frail older adults and those with serious comorbid conditions (i.e., severe hepatic, pulmonary, or renal failure or active or inoperable cancer).
2.1.3. Chronic Kidney Disease
The following recommendations have been added to the PCI Focused Update in accordance with new recommendations appearing in the 2007 UA/NSTEMI Guidelines14 (Table 9). Supporting text from that guidelines statement is presented in the following paragraphs.
Chronic kidney disease (CKD) is not only a coronary risk equivalent for ascertainment of coronary risk but also a risk factor for the development and progression of cardiovascular disease (CVD).63 CKD constitutes a risk factor for adverse outcomes after MI,64 including NSTEMI and other coronary patient subsets. In the highly validated GRACE risk score, serum creatinine is 1 of 8 independent predictors of death.20,65 In 1 recent study, even early CKD constituted a significant risk factor for cardiovascular events and death.64,66 CKD also predicts an increase in recurrent cardiovascular events.67 Cardiovascular death is 10 to 30 times higher in dialysis patients than in the general population. The underrepresentation of patients with renal disease in randomized controlled trials of CVD is a concern.68 Current opinion and most of the limited evidence available suggest that when appropriately monitored, cardiovascular medications and interventional strategies can be applied safely in those with renal impairment and provide therapeutic benefit.64 However, not all recent evidence is consistent with this premise: atorvastatin did not significantly reduce the primary end point of cardiovascular death, nonfatal MI, or stroke in a prospective randomized trial of patients with diabetes and end-stage CKD who were undergoing hemodialysis.69 The preference for primary PCI has also been questioned.70
Particularly in the setting of ACS, bleeding complications are higher in this patient subgroup because of platelet dysfunction and dosing errors; benefits of fibrinolytic therapy, antiplatelet agents, and anticoagulants can be negated or outweighed by bleeding complications; and renin-angiotensin-aldosterone inhibitors can impose a greater risk because of the complications of hyperkalemia and worsening renal function in the patient with CKD. Angiography carries an increased risk of contrast-induced nephropathy; the usual benefits of PCI can be lessened or abolished; and PCI in patients with CKD is associated with a higher rate of early and late complications of bleeding, restenosis, and death.68 Thus, identification of CKD is important in that it represents an ACS subgroup with a far more adverse prognosis but for whom interventions have less certain benefit.
Coronary arteriography is a frequent component of the care of ACS patients. As such, contrast-induced nephropathy can constitute a serious complication of diagnostic and interventional procedures. In patients with CKD or CKD and diabetes, isosmolar contrast material lessens the rise in creatinine and is associated with lower rates of contrast-induced nephropathy than low-osmolar contrast media. This has been documented in a randomized clinical trial (RECOVER [Renal Toxicity Evaluation and Comparison Between Visipaque (Iodixanol) and Hexabrix (Ioxaglate) in Patients With Renal Insufficiency Undergoing Coronary Angiography]) comparing iodixanol with ioxaglate71 and in a meta-analysis of 2727 patients from 16 randomized clinical trials.72
Identification of patients with CKD as recommended in the AHA Science Advisory on Detection of CKD in patients with or at increased risk of CVD should guide the use of isosmolar contrast agents.63 The advisory, which was developed in collaboration with the National Kidney Foundation, recommends that all patients with CVD be screened for evidence of kidney disease by estimating glomerular filtration rate, testing for microalbuminuria, and measuring the albumin-to-creatinine ratio. A glomerular filtration rate of less than 60 ml per min per 1.73 square meters of body surface should be regarded as abnormal. Furthermore, the albumin-to-creatinine ratio should be used to screen for the presence of kidney damage in adult patients with CVD, with values greater than 30 mg of albumin per 1 g of creatinine considered abnormal.
A diagnosis of renal dysfunction is critical to proper medical therapy for UA/NSTEMI. Many cardiovascular drugs used in patients with UA/NSTEMI are renally cleared; their doses should be adjusted for estimated creatinine clearance [see also Section 3 of the 2007 UA/NSTEMI Guidelines14]. In a large community-based registry study, 42% of patients with UA/NSTEMI received excessive initial dosing of at least 1 antiplatelet or antithrombin agent (unfractionated heparin [UFH], LMWH, or GP IIb/IIIa inhibitor).73 Renal insufficiency was an independent predictor of excessive dosing. Dosing errors predicted an increased risk of major bleeding. Clinical studies and labeling that defines adjustments for several of these drugs have been based on the Cockcroft-Gault formula for estimating creatinine clearance, which is not identical to the Modification of Diet and Renal Disease (MDRD) formula. Use of the Cockcroft-Gault formula to generate dose adjustments is recommended. The impact of renal dysfunction on biomarkers of necrosis (i.e., troponin) is discussed in Section 126.96.36.199.1 of the 2007 UA/NSTEMI Guidelines.14
To increase the meager evidence base and to optimize care for this growing high-risk population, the recognition of CKD patients with or at risk of CVD and the inclusion and reporting of renal disease in large CVD trials must be increased in the future.
3. Facilitated PCI
Facilitated PCI refers to a strategy of planned immediate PCI after administration of an initial pharmacological regimen intended to improve coronary patency before the procedure. These regimens have included high-dose heparin, platelet GP IIb/IIIa inhibitors, full-dose or reduced-dose fibrinolytic therapy, and the combination of a GP IIb/IIIa inhibitor with a reduced-dose fibrinolytic agent (e.g., fibrinolytic dose typically reduced 50%). Facilitated PCI should be differentiated from primary PCI without fibrinolytic therapy, from primary PCI with a GP IIb/IIIa inhibitor started at the time of PCI, from early or delayed PCI after successful fibrinolytic therapy, and from rescue PCI after unsuccessful fibrinolytic therapy. Potential advantages of facilitated PCI include earlier time to reperfusion, smaller infarct size, improved patient stability, lower infarct artery thrombus burden, greater procedural success rates, higher TIMI flow rates, and improved survival rates. Potential risks include increased bleeding complications, especially in older patients; potential limitations include added cost.
Despite the potential advantages, clinical trials of facilitated PCI have not demonstrated any benefit in reducing infarct size or improving outcomes. The largest of these was the ASSENT-4 (Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention) PCI trial,5 in which 1667 patients were randomized to full-dose tenecteplase and PCI versus primary PCI. The trial was terminated prematurely because of a higher in-hospital mortality rate in the facilitated PCI group (6% vs. 3%, p = 0.01). The primary end point, a composite of death, shock, and congestive heart failure within 90 days, was significantly higher with facilitated PCI than with primary PCI (18.6% vs. 13.4%; p = 0.0045), and there was a trend toward higher 90-day mortality (6.7% vs. 4.9%; p = 0.14). Defenders of the facilitated PCI strategy point out that the absence of an infusion of heparin after bolus administration and of a loading dose of clopidogrel, plus prohibition of GP IIb/IIIa inhibitors except in bail-out situations, made adjunctive antithrombotic therapy suboptimal for the facilitated PCI group. Moreover, the median treatment delay between tenecteplase and PCI was only 104 minutes, and mortality rates with facilitated PCI were higher in PCI centers. Whether earlier (pre-hospital) administration of fibrinolytic therapy, better antithrombotic therapy, longer delays to PCI, or selective use of PCI as a rescue strategy would make the facilitated PCI strategy beneficial is unclear and requires further study. On the basis of these data, however, facilitated PCI offered no clinical benefit.
Keeley and coworkers performed a quantitative review of 17 trials that compared facilitated PCI and primary PCI74 (Figure 4). Included were 9 trials with GP IIb/IIIa inhibitors alone (n = 1148), 6 trials with fibrinolytic therapy (including ASSENT-4 PCI) (n = 2953), and 2 trials with a fibrinolytic agent plus a GP IIb/IIIa inhibitor (n = 399). Facilitated PCI with fibrinolytic therapy had significantly higher rates of mortality, nonfatal reinfarction, urgent target vessel revascularization, total and hemorrhagic stroke, and major bleeding compared with primary PCI. There were no differences in efficacy or safety when facilitated PCI with a GP IIb/IIIa inhibitor was compared with primary PCI.
A planned reperfusion strategy using full-dose fibrinolytic therapy followed by immediate PCI may be harmful (Table 10). Nevertheless, selective use of the facilitated strategy with regimens other than full-dose fibrinolytic therapy in high-risk subgroups of patients (large MI or hemodynamic or electrical instability) with low bleeding risk who present to hospitals without PCI capability might be performed when transfer delays for primary PCI are anticipated. Although the quantitative analysis showed no advantage for pretreatment with a GP IIb/IIIa inhibitor, neither did it document any major disadvantage. The use of GP IIb/IIIa inhibitors, particularly abciximab, during primary PCI is well established. Further trials of reduced-dose fibrinolytic therapy, with or without GP IIb/IIIa inhibitors, are in progress and may yield different efficacy and/or safety results. For further clarification, please see Section 188.8.131.52.2.1 of the 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction.75
Pharmacological reperfusion with full-dose fibrinolysis is not uniformly successful in restoring antegrade flow in the infarct artery. In such situations, a strategy of prompt coronary angiography with intent to perform PCI is frequently contemplated. In certain patients, such as those with cardiogenic shock (especially in those less than 75 years of age), severe congestive heart failure/pulmonary edema, or hemodynamically compromising ventricular arrhythmias (regardless of age), a strategy of coronary angiography with intent to perform PCI is a useful approach regardless of the time since initiation of fibrinolytic therapy, provided further invasive management is not considered futile or unsuitable given the clinical circumstances (Table 11). Further discussion of the management of such patients may be found in Section 5.4.4 (which has been updated in this document) of the 2005 PCI Guideline Update.13a
4. Rescue PCI
In other patients who do not exhibit the clinical instability noted above, PCI may also be reasonable if there is clinical suspicion of failure of fibrinolysis. This is referred to as rescue PCI. Critical to the success of rescue PCI is the initial clinical identification of patients who are suspected of having failed reperfusion with full-dose fibrinolysis. Because the presence or absence of ischemic discomfort may be unreliable for identifying failed reperfusion, clinicians should search for evidence of inadequate ST-segment resolution on the 12-lead ECG. Operationally, the 12-lead ECG should be scrutinized after adequate time has elapsed before making the judgment that fibrinolytic therapy has not been effective. Although earlier periods have been used in some studies, the writing committee felt that 90 minutes after initiation of fibrinolysis provided the best time for evaluating the need for rescue PCI: hence, if there is less than 50% ST resolution in the lead showing the greatest degree of ST-segment elevation at presentation, fibrinolytic therapy has likely failed to produce reperfusion.
The 2005 PCI Guideline Update13a recommendations for rescue PCI were based on observational data and 2 small randomized clinical trials (n = 179) from the early 1990s.94,95 More recently, MERLIN (Middlesbrough Early Revascularization to Limit Infarction) (n = 307) and REACT (Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis) (n = 427) and 3 meta-analyses have refocused attention on rescue PCI.96–100 This subject has been studied with fewer than 1000 patients enrolled in randomized trials.
In the period between trials studying rescue PCI, there was a transition between angiographic and electrocardiographic diagnosis to detect failed reperfusion. Importantly, in the earlier studies, rescue PCI was performed in infarct arteries with TIMI 0/1 flow, often after a protocol-mandated 90-minute angiogram. In MERLIN and REACT, however, patients were randomized if they had less than 50% ST-segment elevation resolution at 60 or 90 minutes, respectively. Many patients had patent infarct arteries at angiography; only 54% of patients in MERLIN and 74% of patients in REACT (which required less than TIMI grade 3 flow for PCI) actually underwent PCI. From a procedural standpoint, stents have replaced balloon angioplasty, antiplatelet therapy has improved with the addition of a thienopyridine agent and often a GP IIb/IIIa receptor antagonist, and procedural success rates are higher.
Despite these historical differences, recent data support the initial observation that rescue PCI decreases adverse clinical events compared with medical therapy. In the Wijeysundera meta-analysis100) (Figure 5, there was a trend toward reduced mortality rates with rescue PCI from 10.4% to 7.3% (RR 0.69 [95% CI 0.46 to 1.05]; p = 0.09), reduced reinfarction rates from 10.7% to 6.1% (RR 0.58 [95% CI 0.35 to 0.97]; p = 0.04), and reduced HF rates from 17.8% to 12.7% (RR 0.73 [95% CI 0.54 to 1.00]; p = 0.05). These event rates suggest that high-risk patients were selected for enrollment, so these data do not define the role of rescue PCI in lower-risk patients. Also, the benefits of rescue PCI need to be balanced against the risk. There was an excess occurrence of stroke in 2 trials (10 events versus 2 events), but the majority were thromboembolic rather than hemorrhagic, and the sample size was small, so more data are required to define this risk. There was also an increase of 13% in absolute risk of bleeding, suggesting that adjustments in antithrombotic medication dosing are needed to improve safety. It should be noted that the majority of patients who underwent rescue PCI received streptokinase as fibrinolytic therapy.
Given the association between bleeding events and subsequent ischemic events,103 it might be reasonable to select moderate- and high-risk patients for PCI after fibrinolysis and to treat low-risk patients with medical therapy. As noted above, patients with cardiogenic shock, severe HF, or hemodynamically compromising ventricular arrhythmias are excellent candidates. An electrocardiographic estimate of potential infarct size in patients with persistent ST-segment elevation (less than 50% resolution at 90 minutes after initiation of fibrinolytic therapy in the lead showing the worst initial elevation) and ongoing ischemic pain is useful in selecting other patients for rescue PCI. Anterior MI or inferior MI with right ventricular involvement or precordial ST-segment depression usually predicts increased risk.104 Conversely, patients with symptom resolution, improving ST-segment elevation (less than 50% resolution), or inferior MI localized to 3 ECG leads probably should not be referred for angiography. Likewise, it is doubtful that PCI of a branch artery (diagonal or obtuse marginal branch) will change prognosis in the absence of the high-risk criteria noted above.
5. PCI After Fibrinolysis or for Patients Not Undergoing Primary Reperfusion
The open artery hypothesis suggests that late patency of an infarct artery is associated with improved LV function, increased electrical stability, and provision of collateral vessels to other coronary beds for protection against future events (see Table 12). The OAT (Occluded Artery Trial)12 tested the hypothesis that routine PCI for total occlusion 3 to 28 days after MI would reduce the composite of death, reinfarction, or Class IV heart failure. Stable patients (n = 2166) with an occluded infarct artery after MI (about 20% of whom received fibrinolytic therapy for the index event) were randomized to optimal medical therapy and PCI with stenting or optimal medical therapy alone. The qualifying period of 3 to 28 days was based on calendar days; thus, the minimal time from symptom onset to angiography was just over 24 hours. Inclusion criteria included total occlusion of the infarct-related artery with TIMI grade 0 or 1 antegrade flow and LV ejection fraction (LVEF) less than 50% or proximal occlusion of a major epicardial artery with a large risk region. Exclusion criteria included NYHA Class III or IV heart failure, serum creatinine greater than 2.5 mg per dL, left main or 3-vessel disease, clinical instability, or severe inducible ischemia on stress testing if the infarct zone was not akinetic or dyskinetic. The 4-year cumulative end point was 17.2% in the PCI group and 15.6% in the medical therapy group (HR 1.16 [95% CI 0.92 to 1.45] p = 0.2). Reinfarction rates tended to be higher in the PCI group, which may have attenuated any benefit in LV remodeling. There was no interaction between treatment effect and any subgroup variable.
Preclinical studies have suggested that late opening of an occluded infarct artery may reduce adverse LV remodeling and preserve LV volumes. However, 5 previous clinical studies in 363 patients have demonstrated inconsistent improvement in LVEF or LV end-systolic and end-diastolic volumes after PCI. The largest of these, the DECOPI (DEsobstruction COronaire en Post-Infarctus) trial, found a higher LVEF at 6 months with PCI.105 TOSCA-2 (Total Occlusion Study of Canada)13 enrolled 381 stable patients in a mechanistic ancillary study of OAT and had the same eligibility criteria.12 The PCI procedure success rate was 92% and the complication rate was 3%, although 9% had periprocedural MI as measured by biomarkers. At 1 year, patency rates (n = 332) were higher with PCI (83% vs. 25%; p less than 0.0001), but each group (n = 286) had equivalent improvement in LVEF (4.2% vs. 3.5%; p = 0.47). There was modest benefit of PCI on preventing LV dilation over 1 year in a multivariate model, but only 42% had paired volume determinations, so it is unclear whether this finding extends to the whole cohort. The potential benefit of PCI in attenuating remodeling may have been decreased by periprocedural MI and the high rate of use of beta blockers and ACE inhibitors. There was no significant interaction between treatment effect and time, infarct artery, or infarct size.
6. Ancillary Therapy for Patients Undergoing PCI for STEMI
The 2007 STEMI Guidelines Focused Update106 includes a new section on the use of anticoagulant therapy for patients undergoing PCI to establish reperfusion for STEMI. The recommendations associated with PCI are summarized in Table 13.
Full discussion of the background and basis of these recommendations may be found in the 2007 STEMI Guidelines Focused Update. When moving to PCI after fibrinolytic therapy, those patients who received upstream UFH or enoxaparin can continue to receive those anticoagulants in a seamless fashion (i.e., without crossover to another agent) under the dosing regimens listed in the recommendations.106,107 On the basis of reports of catheter thrombosis with fondaparinux alone during primary PCI in OASIS-6 (Organization for Assessment of Strategies for Ischemic Syndromes)7 and the experience with fondaparinux in the OASIS-5 trial,108 the STEMI focused update writing group recommended that fondaparinux should not be used as the sole anticoagulant during PCI but should be coupled with an additional agent that has anti-IIa activity to ameliorate the risk of catheter complications. Although bivalirudin or UFH are potential options for supplemental anticoagulation with fondaparinux, the available experience, albeit limited, is largely with UFH. The only available data from the CREATE (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment) trial that bear on this point are with UFH.109
Given the complexities of the characteristics of the individual agents and their actions on the coagulation cascade, clinicians are cautioned about extrapolating any of the observations with agents discussed in this update to other anticoagulant regimens. In particular, as noted by the Food and Drug Administration (FDA), the LMWHs are sufficiently distinct that they should be evaluated individually rather than considered as a class of interchangeable agents.110
7. Antiplatelet Therapy
The 2005 PCI Guideline Update13a recommended aspirin antiplatelet therapy of 325 mg, which was based primarily on results from the TAXUS IV and SIRIUS trials.111–128 Since that time, experience has been gained with doses of aspirin ranging from 75 mg to 325 mg (see Table 14 for further information and Table 15 for a list of the trials). No significant trials have been reported comparing lower-dose aspirin (75 mg to 100 mg) with higher-dose aspirin (162 mg to 325 mg) in subacute or late stent thrombosis with the incidence of bleeding as the initial course of therapy after placement of drug-eluting stents (DES). Two major trials129,130 involving patients not undergoing placement of DES report an increase in risk of bleeding on higher-dose aspirin. No conclusive data are available regarding higher-dose aspirin and subacute stent thrombosis among patients who are considered aspirin resistant.
Continued treatment with the combination of aspirin and clopidogrel after PCI appears to reduce rates of cardiovascular ischemic events.130,131 On the basis of randomized clinical trial protocols, aspirin 162 mg to 325 mg daily should be given for at least 1 month after implantation of a bare-metal stent (BMS), 3 months after implantation of a sirolimus-eluting stent (SES), and 6 months after implantation of a paclitaxel-eluting stent (PES), after which daily long-term use of aspirin should be continued indefinitely at a dose of 75 mg to 162 mg. In patients for whom there is concern about bleeding, the opinion of the writing group is that lower doses of aspirin—75 mg to 162 mg—can be used.
Likewise, clopidogrel 75 mg daily should be given for a minimum of 1 month after implantation of a BMS [minimum 2 weeks for patients at significant increased risk of bleeding132] and for 12 months after implantation of a SES or PES and ideally in all patients post PCI who are not at high risk of bleeding. Under urgent circumstances that prevent the use of clopidogrel for 1 year, the duration studied for FDA approvals was 3 months for an SES and 6 months for a PES. The optimal duration of clopidogrel therapy after 1 year has not been established and should depend on the judgment of the risk–benefit ratio for the individual patient. Predictors of late stent thrombosis have included stenting of small vessels, multiple lesions, long stents, overlapping stents, ostial or bifurcation lesions, prior brachytherapy, suboptimal stent result, low ejection fraction, advanced age, diabetes mellitus, renal failure, ACS, and premature discontinuation of antiplatelet agents.133,134 Patients should be counseled on the need for and risks of DAT before placement of intracoronary stents, especially a DES, and alternative therapies to pursue if they are unwilling or unable to comply with the recommended duration of DAT. To reduce the incidence of bleeding complications associated with DAT, lower-dose aspirin (75 mg to 162 mg daily) is reasonable for long-term therapy.135,136 Given the importance of a 1-year course of DAT, it is recommended that elective surgery be postponed for 1 year, and among those patients for whom surgery cannot be deferred, aspirin therapy should be considered during the perioperative period in high-risk patients with DES.133
Several investigations have explored various loading doses of clopidogrel before or during PCI. Consistent findings are that compared with a 300-mg loading dose, doses of either 600 or 900 mg achieve greater degrees of platelet inhibition with less variability among patients.137 Fewer patients may demonstrate “resistance” or nonresponsiveness to clopidogrel following the 600-mg dose. There appears to be no significant additive value of the 900-mg dose over the 600-mg dose.137
The 600-mg dose appears to achieve maximum inhibition more rapidly than the 300-mg dose.138 Superior clinical outcomes at 30 days, primarily reduction in evidence of MI, have been reported after the 600-mg dose given 2 hours before the procedure, although this salutary effect was not confirmed in 1 investigation.139 No excess hazard has been reported with the 600-mg compared with the 300-mg dose for patients treated with fibrinolytic therapy; however, loading doses greater than 300 mg have not been studied.140 Larger trials will more fully evaluate higher doses of clopidogrel on clinical events, as well as further evaluate safety (e.g., bleeding). The OASIS-7 trial is comparing 600-mg with 300-mg loading doses of clopidogrel and will provide further evidence about the optimal treatment strategy.
There is agreement that the loading dose should be administered before PCI. What is unclear is the precise time when the loading dose must be given to achieve a desirable therapeutic effect. Evidence from the CREDO (Clopidogrel for the Reduction of Events During Observation) trial suggests that with a 300-mg dose, 6 hours is the minimum time.131 With the 600-mg dose, 2 hours may be sufficient (141), although maximal platelet inhibition may not be achieved until 3 to 4 hours.142
Long-term clopidogrel therapy alone may not achieve adequate inhibition for PCI. Patients on long-term therapy with clopidogrel experience significant additional incremental inhibition of platelet aggregation when given a loading dose.143 In patients treated with fibrinolytic therapy, however, loading doses of greater than 300 mg have not been studied.144
8. Bare-Metal and Drug-Eluting Stents
8.1. Selection of a Bare-Metal or Drug-Eluting Stent
Observational studies indicate that physicians routinely implant stents when performing coronary interventions. Two types of stents are available: BMS and DES. Drug-eluting stents have become increasingly popular as standard therapy. In 2005, a sampling of 140 US hospitals indicated that 94% of patients treated with a stent received at least 1 DES.145 More recently, however, because of concerns about stent thrombosis and the mandate that each DES-treated patient take prolonged DAT, the proportion of DES use has declined to 60% to 70%.
The results of the clinical trials that led to FDA approval of the DES provide support for its use in suitable patients. Extended follow-up of the initial investigated patient cohorts to 4 years confirms the sustained benefit of DES in decreasing the need for repeat revascularization but without differences in death or MI.146–148 Randomized clinical trials in selected clinical subsets such as BMS in-stent restenosis, total occlusions, diabetes mellitus, and small-diameter arteries have also demonstrated the value of DES and have prompted physicians to extend the application of DES beyond the narrow patient populations included in the initial approval trials.122,126,149–154 The duration of follow-up of these “off-label” studies and the small number of patients enrolled, however, limit the detection of subtle differences in important end points such as stent thrombosis, death, or MI.
It is important to recognize certain differences between the BMS and DES when selecting a stent for an individual patient or lesion. First, in general, a DES may be more difficult to implant than a BMS. The DES has a polymer coating that stiffens the stent and makes it less conformable. Accordingly, one reason for using a BMS is that it can be used in patients in whom a DES cannot be implanted successfully. Second, the DES is substantially more expensive than the BMS. When financial resources are limited, use of the DES may be rationed, with implantation only in those patients at greatest risk for restenosis.
A third but very important difference relates to the inhibition of endothelial coverage of the DES and the need for extended DAT (Table 16). After introduction of the BMS, it was associated with a disturbingly high incidence of stent thrombosis.141 Stent thrombosis often presented as MI or even death and usually occurred in the first 30 days after implantation. Changes in technique such as high inflation pressure and intravascular ultrasound (IVUS)-guided deployment and use of concomitant combined aspirin and thienopyridine therapy substantially reduced the incidence of stent thrombosis to a clinically acceptable level.155 Importantly, the requisite duration of DAT was only 4 weeks, and some advocated only 2 weeks. The importance of DAT in preventing stent thrombosis was further strengthened by the outcome of patients for whom DAT was discontinued prematurely because of the need for those patients to undergo surgical procedures. These patients experienced a disturbingly high incidence of stent thrombosis.156 The critical role of DAT in preventing stent thrombosis was also noted among patients with BMS who had received brachytherapy for in-stent restenosis. Presumably these patients were less likely to develop subsequent neointimal coverage of the endoluminal stent surface and were accordingly then more susceptible to stent thrombosis.
In the initial randomized trials that compared the DES with BMS, DAT was administered for 30 days to 6 months. The most recent guidelines update describes a minimum duration of 3 months of DAT for an SES and 6 months for a PES. On the basis of results from other trials that suggest a sustained benefit of DAT, these guidelines further state that ideally DAT should be extended to 12 months. Although these recommendations were to some extent arbitrary, subsequent studies have confirmed that premature discontinuation of DAT, that is, at a time less than “minimal duration” (3 months for the SES and 6 months for the PES) was highly associated with stent thrombosis.157
The tight relationship between DAT and stent thrombosis for patients treated with DES warrants emphasis and has implications for selecting the type of stent deployed at the time of PCI. For example, the clinician should not select a DES for a patient who does not have access to DAT for financial reasons or who is unlikely to be compliant in taking DAT. One study revealed that 14% of patients had stopped DAT 1 month after implantation of the DES.158 Also, implantation of a BMS may be more appropriate in a patient with a known increased risk of bleeding. In situations such as these, the consequences of developing restenosis are considered less untoward than those of stent thrombosis or significant bleeding.
Furthermore, prescribed premature discontinuation of DAT in patients treated with a DES should not be done casually. For example, routine dental procedures should not justify cessation of DAT even though it is anticipated DAT will be subsequently resumed.133 Consideration should be given to delay scheduling of elective procedures that normally warrant discontinuation of antiplatelet agents. The benefit of DES in reducing the need for target vessel revascularization (TVR) also should be taken into account. Some registries have shown 1-digit TVR rates with the BMS, and the absolute reduction in these events using the DES depends on patient and lesion characteristics.
There are also concerns related to the appropriate duration of DAT. More recently, the occurrence of late (up to 1 year) or very late (beyond 1 year) stent thrombosis among DES-treated patients has been described.159 One database analysis suggests that extended use of DAT may have value in preventing late stent thrombosis, whereas others disagree.160
Outcomes of patients in the initial FDA-approval trials to 4 years provides reassurance that, at least for those types of patients, despite a small excess of stent thrombosis, there appears to be no increase in death or MI when comparing DES-treated groups with BMS-treated groups. As noted, protocol-recommended DAT in these patients was not more than 6 months, although extended DAT was not prohibited. (These results are observed despite a significant excess occurrence of stent thrombosis among patients who received a paclitaxel stent.) Some have postulated that the substantial additional revascularization procedures experienced by BMS patients were associated with a small but significant excess rate of death and MI that offset any deaths or MIs that may have occurred in the DES group related to stent thrombosis.
Less data are available regarding the outcomes of patients who receive a DES for an “off-label” indication. Such patients have characteristics of their coronary disease, for example, a lesion in an artery less than 2.5 mm in diameter, very long lesions, bifurcation lesions, or a clinical syndrome such as acute MI, that were excluded in the FDA-approval trials. Reports from large observational studies indicate that “off-label” patients may experience higher rates of repeat revascularization and death and MI at 1 year than DES patients with “on-label” features. Importantly, a similar relationship is observed for patients treated with a BMS. In addition, there appears to be a significant association between “off-label” use and stent thrombosis. Accordingly, the appropriate selection for DAT among “off-label” DES patients may be different than for “on-label” patients.
At this point in time, 12 months of DAT is recommended for all patients who receive a DES120 (see Section 6.2.1) unless there is a high risk of bleeding. The benefits and indications for treatment with DAT beyond 1 year in patients with DES are the subject of ongoing studies. Low-dose aspirin should be continued indefinitely. For patients with clinical features associated with stent thrombosis, such as renal insufficiency, diabetes, or procedural characteristics such as multiple stents or treatment of a bifurcation lesion, extended DAT beyond 1 year may be reasonable. The risk of stent thrombosis needs to be balanced with other medical conditions and nonmedical factors that might affect the risk-benefit ratio of DAT versus other therapies. Finally, certain DES-treated patients have already discontinued DAT 1 year after stent implantation. No information yet supports restarting DAT in these patients.
9. Secondary Prevention
Table 17⇓⇓⇓⇓ presents revised recommendations based on the 2006 AHA/ACC Secondary Prevention Guidelines for Patients with Coronary and Other Atherosclerotic Vascular Diseases.11 This table replaces Table 26 from the 2005 PCI Guideline Update.13a Classes of recommendation and a corresponding level of evidence have been added for all recommendations. There is a new recommendation for annual influenza vaccination, and the section on antiplatelet agents/anticoagulants has been modified slightly to reflect the recent evidence on aspirin dosage in patients who have undergone PCI with stent placement. Other changes since publication of the 2006 ACC/AHA Secondary Prevention Guidelines include the addition of recommended daily physical activity and a Class IIa recommendation for lowered low-density lipoprotein cholesterol.76–92
American College of Cardiology Foundation
John C. Lewin, MD, Chief Executive Officer
Charlene May, Director, Clinical Policy and Documents
Lisa Bradfield, Associate Director, Practice Guidelines
Kristen N. Fobbs, MS, Senior Specialist, Practice Guidelines
Mark D. Stewart, MPH, Associate Director, Evidence- Based Medicine
Sue Keller, BSN, MPH, Senior Specialist, Evidence- Based Medicine
Erin A. Barrett, Senior Specialist, Clinical Policy and Documents
American Heart Association
M. Cass Wheeler, Chief Executive Officer
Rose Marie Robertson, MD, FACC, FAHA, Chief Science Officer
Judy Bezanson, DSN, CNS, RN, Science and Medicine Advisor
↵*Chair of 2005 Writing Committee.
↵†Recused from voting on Section 7: Antiplatelet Therapy.
↵‡Society for Cardiovascular Angiography and Interventions Representative.
↵§Recused from voting on Section 8: Bare-Metal and Drug-Eluting Stents.
↵∥Former Task Force member during this writing effort.
This document is a limited update to the 2005 guideline update and is based on a review of certain evidence, not a full literature review.
This document was approved by the American College of Cardiology Board of Trustees in October 2007, by the American Heart Association Science Advisory and Coordinating Committee in October 2007, and by the Society for Cardiovascular Angiography and Interventions Board of Trustees in November 2007.
The American College of Cardiology Foundation, American Heart Association, and Society for Cardiovascular Angiography and Interventions request that this document be cited as follows: King SB III, Smith SC Jr, Hirshfeld JW Jr, Jacobs AK, Morrison DA, Williams DO. 2007 focused update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: (2007 Writing Group to Review New Evidence and Update the 2005 ACC/AHA/SCAI Guideline Update for Percutaneous Coronary Intervention). Circulation. 2008;117:261–295.
This article has been copublished in the Journal of the American College of Cardiology and e-published in Catheterization and Cardiovascular Interventions.
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Gibbons RJ, Smith S, Antman E. American College of Cardiology/American Heart Association clinical practice guidelines: Part I: where do they come from? Circulation. 107: 2003; 2979–86.
Antman, EM. Manual for ACC/AHA Guideline Writing Committees: Methodologies and Policies from the ACC/AHA Task Force on Practice Guidelines. 2006. Available at: http://www.acc.org/qualityandscience/clinical/manual/pdfs/Methodology.pdf. Accessed September 24, 2007.
Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT–PCI): randomised trial. Lancet. 367: 2006; 569–78.
Bennett JS, Daugherty A, Herrington D, Greenland P, Roberts H, Taubert KA. The use of nonsteroidal anti-inflammatory drugs (NSAIDs): a science advisory from the American Heart Association. Circulation. 111: 2005; 1713–6.
Dzavik V, Buller CE, Lamas GA, et al. Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function: the Total Occlusion Study of Canada (TOSCA)–trial. Circulation. 114: 2006; 2449–57.
Smith SC Jr., Feldman TE, Hirshfeld JW Jr., et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol. 47: 2006; e1–121.
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction). J Am Coll Cardiol. 50: 2007; e1–e157.
Boersma E, Pieper KS, Steyerberg EW, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation. 101: 2000; 2557–67.
Savonitto S, Cohen MG, Politi A, et al. Extent of ST-segment depression and cardiac events in non–ST-segment elevation acute coronary syndromes. Eur Heart J. 26: 2005; 2106–13.
Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non–Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) IIB trial. Circulation. 100: 1999; 1593–601.
Morrow DA, Antman EM, Snapinn SM, McCabe CH, Theroux P, Braunwald E. An integrated clinical approach to predicting the benefit of tirofiban in non-ST elevation acute coronary syndromes. Application of the TIMI Risk Score for UA/NSTEMI in PRISM-PLUS. Eur Heart J. 23: 2002; 223–9.
Wu AH, Apple FS, Gibler WB, Jesse RL, Warshaw MM, Valdes R Jr. National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem. 45: 1999; 1104–21.
Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation. 97: 1998; 1195–206.
Adams JE III, Abendschein DR, Jaffe AS. Biochemical markers of myocardial injury. Is MB creatine kinase the choice for the 1990s? Circulation. 88: 1993; 750–63.
Renkin J, Wijns W, Ladha Z, Col J. Reversal of segmental hypokinesis by coronary angioplasty in patients with unstable angina, persistent T wave inversion, and left anterior descending coronary artery stenosis. Additional evidence for myocardial stunning in humans. Circulation. 82: 1990; 913–21.
Rouan GW, Lee TH, Cook EF, Brand DA, Weisberg MC, Goldman L. Clinical characteristics and outcome of acute myocardial infarction in patients with initially normal or nonspecific electrocardiograms (a report from the Multicenter Chest Pain Study). Am J Cardiol. 64: 1989; 1087–92.
Cannon CP, McCabe CH, Stone PH, et al. The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia. J Am Coll Cardiol. 30: 1997; 133–40.
Holmes DR Jr., Berger PB, Hochman JS, et al. Cardiogenic shock in patients with acute ischemic syndromes with and without ST-segment elevation. Circulation. 100: 1999; 2067–73.
Braunwald E, Mark DB, Jones RH, et al. Unstable Angina: Diagnosis and Management. 1994;3-1-AHCPR Publication No 94-0602:1-154.
Cannon CP. Revascularisation for everyone? Eur Heart J. 25: 2004; 1471–2.
Hirsch A, Windhausen F, Tijssen JG, Verheugt FW, Cornel JH, de Winter RJ. Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study. Lancet. 369: 2007; 827–35.
Spacek R, Widimsky P, Straka Z, et al. Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The VINO Study. Eur Heart J. 23: 2002; 230–8.
Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). J Am Coll Cardiol. 41: 2003; 159–68.
Cheitlin MD, Alpert JS, Armstrong WF, et al. ACC/AHA guidelines for the clinical application of echocardiography: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography). Developed in collaboration with the American Society of Echocardiography. Circulation. 95: 1997; 1686–744.
Brosius FC III, Hostetter TH, Kelepouris E, et al. Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease: a science advisory from the American Heart Association Kidney and Cardiovascular Disease Council;the Councils on High Blood Pressure Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention;and the Quality of Care and Outcomes Research Interdisciplinary Working Group: developed in collaboration with the National Kidney Foundation. Circulation. 114: 2006; 1083–7.
Jo SH, Youn TJ, Koo BK, et al. Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial. J Am Coll Cardiol. 48: 2006; 924–30.
Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol. 44: 2004; E1–E211.
van’t Hof AW, Ernst N, de Boer MJ, et al. Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial. Eur Heart J. 25: 2004; 837–46.
Lee DP, Herity NA, Hiatt BL, et al. Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial. Circulation. 107: 2003; 1497–501.
Mesquita Gabriel H, Oliveira J, Canas da Silva P, et al. Early administration of abciximab bolus in the emergency room improves microperfusion after primary percutaneous coronary intervention, as assessed by TIMI frame count: results of the ERAMI trial (abstr). Eur Heart J. 24: 2003; 543.
Arntz HR, Schroeder J, Pels K, Schwimmbeck P, Witzenbichler B, Schultheiss H. Prehospital versus periprocedural administration of abciximab in STEMI: early and late results from the randomised REOMOBILE study (abstr). Eur Heart J. 24: 2003; 268.
Gyongyosi M, Domanovits H, Benzer W, et al. Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion—results of the Austrian multi-centre randomized ReoPro-BRIDGING Study. Eur Heart J. 25: 2004; 2125–33.
Zeymer U, Zahn R, Schiele R, et al. Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTAMI) pilot trial. Eur Heart J. 26: 2005; 1971–7.
van de Werf F, Janssens L, Brzostek T, et al. Short-term effects of early intravenous treatment with a beta-adrenergic blocking agent or a specific bradycardiac agent in patients with acute myocardial infarction receiving thrombolytic therapy. J Am Coll Cardiol. 22: 1993; 407–16.
O’Neill WW, Weintraub R, Grines CL, et al. A prospective, placebo-controlled, randomized trial of intravenous streptokinase and angioplasty versus lone angioplasty therapy of acute myocardial infarction. Circulation. 86: 1992; 1710–7.
Widimsky P, Groch L, Zelizko M, Aschermann M, Bednar F, Suryapranata H. Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study. Eur Heart J. 21: 2000; 823–31.
Vermeer F, Oude Ophuis AJM, vd Berg EJ, et al. Prospective randomised comparison between thrombolysis, rescue PTCA, and primary PTCA in patients with extensive myocardial infarction admitted to a hospital without PTCA facilities: a safety and feasibility study. Heart. 82: 1999; 426–31.
Fernandez-Aviles F, Alonso J, Castor-Beiras A, et al. Primary versus facilitated percutaneous coronary intervention (tenecteplase plus stenting) in patients with ST-elevated myocardial infarction: the final results of the GRACIA–2 randomized trial (abstr). Eur Heart J. 25: 2004; 33.
Facilitated percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: results from the prematurely terminated ADdressing the Value of facilitated ANgioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction (ADVANCE MI) trial. Am Heart J. 150: 2005; 116–22.
Deleted in proof.
Ellis SG, da Silva ER, Heyndrickx G, et al. Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction. Circulation. 90: 1994; 2280–4.
Sutton AG, Campbell PG, Graham R, et al. A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-segment elevation myocardial infarction: the Middlesbrough Early Revascularization to Limit INfarction (MERLIN) trial. J Am Coll Cardiol. 44: 2004; 287–96.
Deleted in proof.
Steg PG, Thuaire C, Himbert D, et al. DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre trial of occluded artery angioplasty after acute myocardial infarction. Eur Heart J. 25: 2004; 2187–94.
Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction. Circulation. 117: 2008; XXX–XXX.
Gibson CM, Murphy SA, Montalescot G, et al. Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial. J Am Coll Cardiol. 49: 2007; 2238–46.
Grube E, Silber S, Hauptmann KE, et al. TAXUS I: six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation. 107: 2003; 38–42.
Colombo A, Drzewiecki J, Banning A, et al. Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions. Circulation. 108: 2003; 788–94.
Tanabe K, Serruys PW, Grube E, et al. TAXUS III trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation. 107: 2003; 559–64.
Lansky AJ, Costa RA, Mintz GS, et al. Non-polymer-based paclitaxel-coated coronary stents for the treatment of patients with de novo coronary lesions: angiographic follow-up of the DELIVER clinical trial. Circulation. 109: 2004; 1948–54.
Gershlick A, De Scheerder I, Chevalier B, et al. Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial. Circulation. 109: 2004; 487–93.
Holmes DR Jr., Leon MB, Moses JW, et al. Analysis of 1-year clinical outcomes in the SIRIUS trial: a randomized trial of a sirolimus-eluting stent versus a standard stent in patients at high risk for coronary restenosis. Circulation. 109: 2004; 634–40.
Stone GW, Ellis SG, Cox DA, et al. One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial. Circulation. 109: 2004; 1942–7.
Dawkins KD, Grube E, Guagliumi G, et al. Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice. Circulation. 112: 2005; 3306–13.
Topol EJ, Easton D, Harrington RA, et al. Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease. Circulation. 108: 2003; 399–406.
Berger PB, Mahaffey KW, Meier SJ, et al. Safety and efficacy of only 2 weeks of ticlopidine therapy in patients at increased risk of coronary stent thrombosis: results from the Antiplatelet Therapy alone versus Lovenox plus Antiplatelet therapy in patients at increased risk of Stent Thrombosis (ATLAST) trial. Am Heart J. 143: 2002; 841–6.
Grines CL, Bonow RO, Casey DE Jr., et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol. 49: 2007; 734–9.
Luscher TF, Steffel J, Eberli FR, et al. Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. Circulation. 115: 2007; 1051–8.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 324: 2002; 71–86.
von Beckerath N, Taubert D, Pogatsa-Murray G, Schomig E, Kastrati A, Schomig A. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) trial. Circulation. 112: 2005; 2946–50.
Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, Tantry US. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study. Circulation. 111: 2005; 1153–9.
Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation. 111: 2005; 2099–106.
Hochholzer W, Trenk D, Frundi D, et al. Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention. Circulation. 111: 2005; 2560–4.
Bates ER, Lau WC, Bleske BE. Loading, pretreatment, and interindividual variability issues with clopidogrel dosing. Circulation. 111: 2005; 2557–9.
Kastrati A, von Beckerath N, Joost A, Pogatsa-Murray G, Gorchakova O, Schomig A. Loading with 600 mg clopidogrel in patients with coronary artery disease with and without chronic clopidogrel therapy. Circulation. 110: 2004; 1916–9.
Williams DO, Abbott JD, Kip KE. Outcomes of 6906 patients undergoing percutaneous coronary intervention in the era of drug-eluting stents: report of the DEScover Registry. Circulation. 114: 2006; 2154–62.
Chieffo A, Morici N, Maisano F, et al. Percutaneous treatment with drug-eluting stent implantation versus bypass surgery for unprotected left main stenosis: a single-center experience. Circulation. 113: 2006; 2542–7.
Sabate M, Jimenez-Quevedo P, Angiolillo DJ, et al. Randomized comparison of sirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients: the diabetes and sirolimus-eluting stent (DIABETES) trial. Circulation. 112: 2005; 2175–83.
Neumann FJ, Desmet W, Grube E, et al. Effectiveness and safety of sirolimus-eluting stents in the treatment of restenosis after coronary stent placement. Circulation. 111: 2005; 2107–11.
Suttorp MJ, Laarman GJ, Rahel BM, et al. Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II): a randomized comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions. Circulation. 114: 2006; 921–8.
Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation. 113: 2006; 2803–9.
- 1. Introduction
- 2. Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
- 3. Facilitated PCI
- 4. Rescue PCI
- 5. PCI After Fibrinolysis or for Patients Not Undergoing Primary Reperfusion
- 6. Ancillary Therapy for Patients Undergoing PCI for STEMI
- 7. Antiplatelet Therapy
- 8. Bare-Metal and Drug-Eluting Stents
- 9. Secondary Prevention
- Figures & Tables
- Supplemental Materials
- Info & Metrics