Author + information
- Received August 26, 2015
- Revision received November 5, 2015
- Accepted November 6, 2015
- Published online January 19, 2016.
- Kevin R. Bainey, MD, MSc and
- Paul W. Armstrong, MD∗ ( )()
- Canadian VIGOUR Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
- ↵∗Reprint requests and correspondence:
Dr. Paul W. Armstrong, Division of Cardiology, 2-132 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
ST-segment elevation myocardial infarction (STEMI) remains a significant global public health concern. Practice guidelines in both the United States and Europe have been major contributors to providing evidence-based care. Rapid advances in contemporary therapies mandate regular and timely updates to guideline recommendations. In the fall of 2012, the European Society of Cardiology published their latest guidelines for the management of STEMI. In 2013 (∼3 months later), the American College of Cardiology Foundation and the American Heart Association jointly published their most recent STEMI guideline statements. In this review, we compare the transatlantic guidelines, highlighting differences in their recommendations and the interpretation of evidence addressing STEMI care.
- acute coronary syndrome
- fibrinolytic therapy
- ischemic time
- percutaneous coronary intervention
- standard of care
Cardiovascular medicine has witnessed remarkable advances in the care of patients with acute coronary syndromes (ACS). This is no more dramatically evident than in the management of myocardial infarction (MI) and is well captured by the evolution of care guidelines first articulated for MI by the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) in 1990 (1) and by the European Society of Cardiology (ESC) in 1996 (2). Subsequently, specific guidelines aimed at ST-segment elevation myocardial infarction (STEMI) emerged on both sides of the Atlantic, along with regular updates that culminated in recent major revisions occurring within 3 months of each other (3,4). Our purpose here is to highlight particular areas where differences exist in either emphasis or interpretation and how they influence the recommendations that follow. In undertaking this review, we are conscious that the target audience for the ACCF/AHA guidelines is more homogeneous than the more eclectic audience for the ESC, which spans a greater diversity of social, economic, and political jurisdictions. In context, we also appreciate that this is a rapidly evolving field, where these recommendations may change on the basis of new evidence forthcoming since their publication (5,6).
Some initial general observations are in order. The 2012 ESC cites 346 references in their 2012 document, whereas the ACCF/AHA cite 656 references (almost double) in their full-text 2013 version. Although both documents use the traditional 3 classes of recommendations and levels of evidence (LOEs), the ACCF/AHA have, for the first time, subdivided the Class III category into those assigned as having no benefit versus those with the potential for harm. Unlike the ESC, the ACCF/AHA guidelines also specifically integrate the classes of recommendation and levels of evidence in an attempt to gauge both the magnitude of expected benefit and the certainty with which it can be anticipated.
As seen in Figure 1, the Europeans provide a larger number of official guideline recommendations (ESC 164 vs. ACCF/AHA 122). Although both sets of guidelines share common themes, as evident in the central panel of Figure 1, there are unique characteristics for each, as noted in the margins (3,4). When these recommendations are categorized according to their respective LOE (Figure 2), the majority from both sets of guidelines are Class I. However, the minority of these Class I recommendations are supported by LOE A (ACCF/AHA 19% vs. ESC 25%). Although this represents a modest improvement over the 10.7% fraction of LOE: A supporting the Class I STEMI recommendations in the 2004 ACCF/AHA STEMI guidelines (7), it also highlights that further evidence is required in areas of clinical need (8).
Both guideline committees endorse the ESC/ACCF/AHA Universal Definition of Myocardial Infarction for the diagnosis of STEMI (9,10). However, given the timing of publication (i.e., after the ESC guidelines), the ACCF/AHA understandably uses a more contemporary definition (i.e., the Third Universal Definition of Myocardial Infarction ). Hence, the ACCF/AHA guidelines include new ST-segment elevation at the J-point in at least 2 contiguous leads ≥2 mm (0.2 mV) in men, ≥1.5 mm (0.15 mV) in women in leads V2 to V3, and/or of ≥1 mm (0.1 mV) in other contiguous chest leads or the limb leads. The ESC defines the STEMI electrocardiogram (ECG) as J-point elevation in 2 contiguous leads with ≥0.25 mV (0.25 mm) in men below the age of 40 years, ≥0.2 mV (0.3 mm) in men over the age of 40 years, or ≥0.15 mV (0.15 mm) in women in leads V2 to V3, and/or ≥0.1 mV (0.1 mm) in other leads. The Europeans also strongly advocate the use of right precordial leads (V3R and V4R) for inferior MI to identify right ventricular involvement and posterior chest leads (V7 to V9 ≥0.05 mV) in patients with suspected posterior (inferobasal) MI (Class IIa, LOE: C).
Interestingly, due to its infrequent occurrence, the ACCF/AHA guidelines have eliminated new left bundle branch block (LBBB) from the diagnosis of STEMI and opine that LBBB “should not be considered diagnostic of acute MI in isolation” (4). However, the ESC still considers atypical electrocardiogram presentations in STEMI, such as LBBB and ventricular paced rhythm, to be worthy potential prospects.
Emergency Supportive Care
Table 1 outlines the recommendations for acute supportive care in patients with STEMI. Although both guidelines advocate compassionate therapies, the ESC provides official recommendations (Class, LOE), whereas the ACCF/AHA guidelines offer advisory statements about these therapies without recommendations.
The ACCF/AHA guidelines suggest morphine as the choice of analgesic agent (opioid) for STEMI to help alleviate anxiety, reduce the work of breathing (particularly in patients with acute pulmonary edema), and help reduce ventricular loading conditions. The ESC is less specific on the choice of analgesic agent, but recommends the general use of intravenous opioids to help relieve pain (Class I, LOE: C).
Inhaled oxygen is promoted by both organizations; however, the ACCF/AHA guidelines are cautious and suggest supplemental oxygen only for arterial saturations <90% due to the 3-fold increased risk of death suggested by a Cochrane review of the data (11) and an observed increase in coronary vascular resistance with oxygen in acute MI (12). The ESC strongly recommends that supplemental oxygen be administered for hypoxia with saturations <95%, breathlessness, or acute heart failure (Class I, LOC: C).
Immediate therapy with aspirin has become standard, given the commensurate benefits observed in the ISIS-2 (Second International Study of Infarct Survival) study (13). In keeping with the oral administration in this trial, the ACCF/AHA guidelines endorse oral administration of aspirin (162- to 325-mg load) in acute MI (Class I, LOE: B). However, the ESC recommends either oral (150 to 300 mg) or intravenous formulation (80 to 150 mg) (Class I, LOE: B). Note that intravenous aspirin is only available in Europe, and hence is not included in the ACCF/AHA guidelines.
Choice of Reperfusion Strategy
Because rapid recanalization of the infarct-related artery is paramount in STEMI, it understandably takes center stage in both task force recommendations. However, this topic also accentuates key transatlantic differences relating to both the modes and timing of reperfusion (Table 2, Central Illustration). The ACCF/AHA guidelines focus on primary percutaneous coronary intervention (PCI) as the leading and preferred mode of reperfusion for patients with STEMI. For patients presenting at a PCI-capable hospital, the recommended first medical contact (FMC)-to-device time is within 90 min. For patients presenting to a non–PCI-capable hospital, immediate transfer to a PCI facility for primary PCI is recommended, with an FMC-to-device time within 120 min. Fibrinolysis is endorsed only if unavoidable delays occur in excess of 120 min (i.e., PCI-related delay) (Class I, LOE: B). Of considerable interest is the differing approach to pre-hospital fibrinolytic therapy. The ACCF/AHA guidelines suggest that this strategy might be useful in rural areas, but notes that such areas have “neither the resources to train paramedics nor the funding for necessary equipment” (4). Remarkably, no recommendation is provided, but rather, a suggestion is made “for further research into the implementation of pre-hospital strategies to reduce total ischemic time” (4).
In contrast, the ESC strongly sanctions pre-hospital logistics of care with a particular focus and Class I, LOE: B recommendation for the use of pre-hospital care as a mode for reducing “system delay” (i.e., FMC to reperfusion) (Central Illustration). If primary PCI is considered, patients arriving at a PCI-capable hospital should achieve an FMC-to-device time within 90 min, but preferably within 60 min of presentation. The ESC further suggests a more stringent ≤60 min FMC-to-device time for high-risk cases, particularly emphasizing those with large anterior infarcts, as well as early presenters (within 2 h) who are expected to derive greater myocardial salvage and incremental benefit from early reperfusion. If presenting at a non–PCI-capable hospital, the ESC recommends an FMC-to-device time within 120 min, but preferably within 90 min. For high-risk cases, FMC-to-device time should be preferably within 60 min, but if these times cannot be achieved (i.e., within 90 min), then the ESC recommends fibrinolysis (Class IIa, LOE: B).
Primary PCI at a high-volume facility, performed by an experienced team with 24 h/7 days/week access, is the preferred reperfusion strategy in patients presenting with STEMI within 12 h of symptom presentation.
Ancillary pharmacological therapy
Table 3 provides a summary of acute pharmacotherapy for primary PCI in STEMI. The ACCF/AHA supports the use of all P2Y12 receptor inhibitors with similar levels of recommendation (clopidogrel, prasugrel, and ticagrelor all receive Class I, LOE: B). The ESC prefers prasugrel or ticagrelor to clopidogrel, unless they are not available or contraindicated (Class I, LOE: C). Intravenous glycoprotein (GP) IIb/IIIa antagonists have a Class IIa ACCF/AHA recommendation (LOE: B [except abciximab, LOE: A]). Intracoronary abciximab is a consideration for use in the catheterization laboratory (Class IIb, LOE: B). Using the same evidence, the ESC provides a weaker Class IIb recommendation for intravenous GP IIb/IIIa antagonists as an adjunct therapy in STEMI (LOE: B [except abciximab, LOE: A]). No official ESC recommendation is provided for intracoronary use.
For primary PCI, the ACCF/AHA guidelines recommend unfractionated heparin (UFH) with a 50 to 70 U/kg bolus if a GP IIb/IIIa antagonist is administered (Class I, LOE: C) or a UFH 70 to 100 U/kg bolus without a GP IIb/IIIa antagonist (Class I, LOE: C). Bivalirudin has a stronger recommendation with or without prior treatment with UFH (Class I, LOE: B) (14,15). Additionally, the ACCF/AHA guidelines recommend bivalirudin over UFH and a GP IIb/IIIa antagonist (Class IIa, LOE: B). The ESC recommends a lower bolus dose of UFH (50 to 60 U/kg) with a GP IIb/IIIa antagonist (Class I, LOE: C) (70 to 100 U/kg bolus without a GP IIb/IIIa antagonist, Class I, LOE: C). Bivalirudin is also preferred over UFH and a GP IIb/IIIa antagonist (Class I, LOE: B). The ESC recommends enoxaparin with or without a GP IIb/IIIa antagonist, which is preferred over UFH (Class IIb, LOE: B). This recommendation was largely supported by the ATOLL (Acute Myocardial Infarction Treated with Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Long-term Follow-up) trial, demonstrating clinical benefit (secondary outcomes) without the increased risk of bleeding (16). Enoxaparin is not included in the ACCF/AHA guidelines for treatment of STEMI with primary PCI.
In patients presenting with >12 h of symptoms, there are differences in the guideline recommendations. In patients with 12 to 24 h of symptoms and evidence of ongoing ischemia, the ACCF/AHA guidelines indicate that PCI should be performed with a weaker recommendation (Class IIa, LOE: B) than the ESC, which more strongly recommends PCI, but with less evidence (Class I, LOE: C). Both guidelines cite Polish observational registry data supporting late reperfusion in STEMI (17). However, for this indication (i.e., ongoing ischemia), the ACCF/AHA guidelines cite the BRAVE (Beyond 12 Hours Reperfusion Alternative Evaluation)-2 trial, which is the only randomized study (n = 347) to address the utility of PCI versus conservative management in stable patients presenting subacutely within 12 to 48 h of symptom onset. In this context, the study found improvements in infarct size with PCI; yet, there was no improvement in clinical outcome at 30 days (18). The ESC guidelines do refer to the BRAVE-2 trial in the context of primary PCI in stable patients (i.e., no evidence of ischemia) presenting 12 to 24 h after symptom onset with a lower recommendation (Class IIb, LOE: B) (18,19). In very late presenters (>24 h) who are clinically stable, the ACCF/AHA guidelines advise against performing PCI (Class III, LOE: B). The ESC provides a similar recommendation, but with a higher level of evidence (Class III, LOE: A). Both guidelines reference OAT (Occluded Artery Trial), which demonstrated no benefit from PCI to an occluded infarct-related artery in the nonacute setting of MI (20).
The ACCF/AHA do not provide guideline recommendations for a preferred vascular access site for cardiac catheterization. In the text, they indicate radial access should be used when feasible. The ESC provides official recommendations supporting the radial approach, particularly if performed by an experienced radial operator (Class IIa, LOE: B). Interestingly, whereas both guidelines reference the RIVAL (RadIal Vs femorAL access for coronary intervention) trial (21), the ACCF/AHA guidelines report that the “rates of major bleeding were not lower with the radial versus femoral access in patients with STEMI” (4), whereas the ESC found “the radial approach reduced the incidence of acute bleeding events especially in ACS” (3).
Stent selection has been controversial since the 2006 BASKET-LATE (BAsel Stent Kosten Effektivitäts Trial—LAte Thrombotic Events) observations (22). The ACCF/AHA guidelines advocate use of a bare-metal stent (BMS) if a high bleeding risk exists or if there are likely to be issues with dual antiplatelet therapy (DAPT) compliance (Class I, LOE: C), given the brief prescribed duration of DAPT (1 month for BMS, according to ACCF/AHA recommendations). Otherwise, DAPT is recommended for 1 year, given the benefits accrued in ACS (Class I, LOE: B). However, if a drug-eluting stent (DES) is placed, clinicians are encouraged to consider DAPT beyond 1 year (Class IIb, LOE: C). No comments are made regarding shortening the duration of DAPT with DES. The ESC prefers DES if no bleeding risk or compliance issues apply (Class IIa, LOE: A). Suggestions for 12 months of DAPT are similar for ACS (Class I, LOE: C); however, the ESC provides a strict minimum of 1 month for BMS (Class I, LOE: C) and 6 months for DES (Class IIb, LOE: B).
Culprit-only versus complete revascularization
Approximately 40% to 50% of patients undergoing primary PCI have multivessel disease, with at least 1 additional noninfarct-related artery lesion considered to be hemodynamically severe. The ACCF/AHA guidelines indicate that PCI should not be performed in a noninfarct artery at the time of primary PCI in hemodynamically stable patients (Class III, LOE: B). The ESC recommends limiting primary PCI to the culprit vessel, with the exception of cardiogenic shock and persistent ischemia after primary PCI (Class IIa, LOE: B). Interestingly, both sets of guidelines cite similar references (23–25).
The ACCF/AHA guidelines recommend PCI of the noninfarct artery at a time separate from primary PCI in patients who have spontaneous symptoms of myocardial ischemia (Class I, LOE: C). In patients with intermediate- or high-risk findings on noninvasive testing, PCI is also considered reasonable in a noninfarct artery at a time separate from the primary PCI (Class IIa, LOE: B). The ESC supports initial stress testing or imaging (e.g., using stress myocardial perfusion scintigraphy, stress echocardiography, positron emission tomography, or cardiac magnetic resonance imaging) for ischemia and viability in patients with multivessel disease or in whom revascularization of other vessels is contemplated (Class I, LOE: A).
Since the publication of the 2012 ESC STEMI guidelines, a more recent ESC recommendation on nonculprit intervention recommends that it be considered as a staged approach in cases of symptomatic ischemia (Class IIA, LOE: B), or even during the index PCI in selected patients (Class IIB, LOE: B) (5). In a 2015 focused update of the 2013 ACCF/AHA STEMI guidelines, the ACC/AHA and Society for Cardiac Angiography and Interventions (SCAI) provide a new recommendation on nonculprit PCI in selected patients who are hemodynamically stable, either during the index procedure or as a staged approach (Class IIB, LOE: B) (6).
Although primary PCI is recommended as the preferred mode of reperfusion in STEMI, the feasibility of achieving this in a timely fashion is much more challenging given geographic constraints, transfer logistics, and recognition of the total elapsed ischemic time. Hence, fibrinolysis has emerged as a reasonable and viable alternative.
Ancillary pharmacological therapy
Table 3 provides a summary of acute pharmacotherapy for fibrinolysis in STEMI. Both the ACCF/AHA and ESC guidelines endorse DAPT with clopidogrel as standard of care (age ≤75 years, 300-mg bolus followed by 75 mg daily) (Class I, LOE: A). However, the ACCF/AHA guidelines recommend 75 mg only in patients age >75 years (Class I, LOE: A), whereas the ESC guidelines make no official recommendation in the elderly. Elderly patients were not excluded in COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) (26), where all patients received a 75-mg clopidogrel load, followed by 75 mg daily, as opposed to CLARITY-TIMI (Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis In Myocardial Infarction)-28, where patients received a 300-mg bolus, followed by 75 mg daily (patients age >75 years excluded) (27).
On the basis of the ASSENT (Assessment of the Safety and Efficacy of a New Thrombolytic)-3 (28) and EXTRACT-TIMI (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment–Thrombolysis In Myocardial Infarction)-25 (29) randomized studies, both guidelines strongly support enoxaparin (compared with UFH) as the preferred parenteral anticoagulant with fibrinolysis (Class I, LOE: A). Fondaparinux is recommended as Class I, LOE: B by the ACCF/AHA guidelines, whereas the ESC tempers its use as a Class IIa, LOE: B indication and, further, recommends that it only be used in conjunction with streptokinase, given the results of the OASIS (Organization for the Assessment of Strategies for Ischemic Syndromes)-6 trial (30,31).
The ESC strongly supports initiation of early fibrinolysis (pre-hospital Class IIa, LOE: A) in early-presenting patients (<2 h of symptoms) with a large infarct territory and low bleeding risk when FMC-to-device time exceeds 90 min (Class IIa, LOE: B) (Table 2). This is largely on the basis of NRMI (National Registry of Myocardial Infarction) data, highlighting the potential benefits of an early presenting, young, anterior MI patient (i.e., a large territory of myocardium at risk) (32). As noted previously, the ACCF/AHA guidelines are largely silent on early (i.e., pre-hospital) administration.
When PCI is unavailable in patients with 12 to 24 h of symptoms who have a large area of myocardium at risk or hemodynamic instability, the ACCF/AHA guidelines indicate that it is reasonable to administer fibrinolysis (Class IIa, LOE: C). The ESC guidelines do not commit to a fibrinolysis strategy beyond 12 h of symptom duration.
Both guidelines support a rescue approach (Class I, LOE: A), given the REACT (Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis) trial supporting the need for rescue PCI when fibrinolysis fails (33,34). Because assessment of reperfusion is paramount following fibrinolysis, the ACCF/AHA guidelines define fibrinolysis failure electrocardiographically as <50% ST-segment resolution in the worst lead at 60 to 90 min following administration. The ESC uses a shorter timeline of <50% ST-segment resolution at 60 min.
Routine transfer to a PCI-capable hospital after fibrinolysis
Following fibrinolysis, a routine strategy of transfer to a PCI-capable hospital may be reasonable (Central Illustration), although logistical constraints and financial barriers may preclude such a strategy for all STEMI patients. The ACCF/AHA guidelines are more selective in their recommendation for transfer. Immediate transfer is suggested for cardiogenic shock or severe acute heart failure, irrespective of time delay from MI onset (Class I, LOE: B). The approach taken for rescue intervention for urgent transfer in cases of failed reperfusion or reocclusion is classified as Class IIa, LOE: B or as part of an invasive strategy in stable patients with PCI between 3 and 24 h after successful fibrinolysis (Class IIa, LOE: B). The ACCF/AHA guidelines contend that this is an unresolved issue, particularly in non–high-risk patients after successful fibrinolysis, and requires further justification. TRANSFER AMI (Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction), which studied high-risk STEMI patients, found that routine transfer to a PCI facility within 6 h improved the 30-day composite outcome of death, shock, heart failure, re-MI, and recurrent ischemia (35). In contrast, the ESC guidelines take a more aggressive unified approach, where transfer is indicated in all patients (irrespective of baseline risk) after fibrinolysis (Class I, LOE: A).
Contraindications to fibrinolysis
Both guidelines report absolute and relative contraindications for fibrinolysis; however, inconsistencies between reported contraindications are apparent (Table 4). The ACCF/AHA guidelines are more liberal with fibrinolysis in patients with a prior ischemic stroke compared with the ESC guidelines (3- vs. 6-month history of prior ischemic stroke). However, the ACCF/AHA guidelines are more conservative in patients with severe uncontrolled hypertension (absolute contraindication), whereas the ESC guidelines list this only as a relative contraindication. The ESC does not recommend fibrinolysis (absolute contraindication) in patients with gastrointestinal bleeding within the past month, or noncompressible punctures within 24 h. These were considered relative contraindications by the ACCF/AHA. The ACCF/AHA guidelines list prior use of streptokinase (within the past 6 months) as an absolute contraindication, but this is not mentioned in the ESC guidelines.
Management of Complications Following STEMI
In the reperfusion era, complications following STEM have become less frequent (36).
Severe heart failure/cardiogenic shock
Both the ACCF/AHA and ESC guidelines support emergent revascularization (PCI or coronary artery bypass graft), irrespective of MI onset, in the setting of shock (Class I, LOE: B). However, when mechanical revascularization is not available, the ACCF/AHA guidelines support fibrinolysis with a strong recommendation (Class I, LOE: B), whereas the ESC’s stance is less enthusiastic (Class IIa, LOE: C). The ACCF/AHA guidelines recommend intra-aortic balloon pump use as reasonable in shock (Class IIa, LOE: B), whereas the ESC guidelines only indicate that its use should be considered (Class IIb, LOE: B). The ESC provides extensive recommendations regarding the acute treatment of heart failure and left ventricular dysfunction according to Killip class. Examples include interval loop diuretic use (i.e., furosemide 20 to 40 mg intravenous every 1 to 4 h) for Killip class II or III heart failure [Class I, LOE: C]), inotropic support (dopamine, dobutamine), including levosimendan for Killip class III heart failure (Class IIb, LOE: C), and norepinephrine (preferred over dopamine) when in cardiogenic shock (Killip class IV) (Class IIb, LOE: B). Ultrafiltration is considered for Killip class III heart failure (Class IIa, LOE: B). The ACCF/AHA guidelines provide limited guidance regarding pharmacological management in this area, but state, “Medical support with inotropes and vasopressor agents should be individualized and guided by invasive hemodynamic monitoring. The use of dopamine in this setting may be associated with excess hazard” (4).
The ESC guidelines provide numerous practice recommendations for acute management of these conditions, whereas the ACCF/AHA guidelines largely refer to the 2010 Advanced Cardiac Life Support guidelines for care as a web-based teaching tool (with no mention of Class or LOE distinction on the website) (Table 5).
Management of Hyperglycemia in the Acute Phase of STEMI
The benefit afforded by intravenous insulin in control of hyperglycemia was noted in the DIGAMI (Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction) trial (37), but could not be replicated in the DIGAMI-2 study (38). Moreover, no benefit toward intensive glucose control was evident in the HI (Hyperglycemia: Intensive Insulin Infusion in Infarction)-5 trial in acute MI (39). Given this ambiguity, the ACCF/AHA guidelines stated that blood glucose should be maintained at <180 mg/dl, while avoiding hypoglycemia. Yet, the ESC devotes an entire section of the guidelines to management of hyperglycemia in the acute phase of STEMI. The goals of glucose control in the acute phase are maintenance of glucose concentrations ≤11.0 mmol/l (200 mg/dl), while avoiding a fall of glycemia <5 mmol/l (<90 mg/dl). In some patients, this may require a dose-adjusted insulin infusion with monitoring of glucose, as long as hypoglycemia is avoided (Class IIa, LOE: B).
Logistics of Intensive Care
The ACCF/AHA guidelines do not provide recommendations pertaining to the logistics of intensive care. However, as part of risk assessment for STEMI, the guidelines support early discharge of stable STEMI patients with a low risk of complications. In particular, among patients with STEMI managed with fibrinolysis, it has been suggested that an uncomplicated course after 72 h of hospitalization identifies a group with sufficiently low risk to enable discharge and is cost-effective (40,41). In comparison, the ESC provides 4 detailed recommendations pertaining to logistical issues for hospital stay with STEMI. In particular, the ESC guidelines reference the results of the PAMI II (Second Primary Angioplasty in Myocardial Infarction Trial) criteria (42) and the Zwolle primary PCI Index (43), promoting early discharge (after approximately 72 h) in selected low-risk patients, provided early rehabilitation and adequate follow-up can be arranged (Class IIb, LOE: B).
Patients presenting with STEMI are at risk of recurrent events and early death (44). With the use of evidence-based treatments, clinical outcomes have improved over time (45). Table 6 provides a brief summary of long-term therapies advocated by each guideline task force for comparison. Although most recommendations are similar, important distinctions are worthy of discussion. The ACCF/AHA guidelines make a less definitive recommendation on the use of maintenance low-dose aspirin (Class IIa, LOE: B) compared with the ESC guidelines (Class I, LOE: A). The European guideline position on low-dose aspirin is supported by the CURRENT-OASIS (Clopidogrel optimal loading dose Usage to Reduce Recurrent EveNTs-Organization to Assess Strategies in Ischemic Syndromes)-7 trial, which demonstrated no clear efficacy and a higher risk of gastrointestinal bleeding compared with regular-dose aspirin (46). Both guidelines support 12 months of P2Y12 inhibitors; however, only the ESC guidelines recommend gastric protection with a proton pump inhibitor in patients on DAPT with a high risk of bleeding complications (Class IIa, LOE: C). The ACCF/AHA guidelines strongly recommend long-term beta-blockers (Class I, LOE: B), whereas the ESC provides a weaker recommendation (Class IIa, LOE: B). Both guidelines strongly recommend angiotensin-converting enzyme inhibitors, particularly in patients with left ventricular systolic dysfunction, heart failure, or anterior location, but the ESC guidelines also add diabetic status as an indication (Class I, LOE: A). Both guidelines list high-dose statin therapy as a Class I recommendation; however, the ACCF/AHA guidelines grade it with a lower level of evidence (LOE: B; ESC LOE: A). Finally, the ESC recommends the use of low-dose rivaroxaban (2.5 mg twice daily) in selected patients who receive aspirin and clopidogrel, provided that the bleeding risk profile is acceptable (Class IIb, LOE: B). This is primarily supported by the results of the ATLAS ACS 2-TIMI-51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2–Thrombolysis In Myocardial Infarction-51) trial (47), which has led to European Medicines Agency approval, but rivaroxaban has yet to be approved by the U.S. Food and Drug Administration.
Sudden Cardiac Death Risk Assessment
The most powerful predictor of sudden cardiac death is reduced left ventricular function (48). In acute MI, left ventricular systolic dysfunction is common, but incremental recovery of stunned myocardium often occurs over a 3-month interval after reperfusion. Hence, re-evaluation of left ventricular function is of fundamental importance in the nonacute setting. The ACCF/AHA guidelines indicate that patients with an initially reduced left ventricular ejection fraction (LVEF) (i.e. ≤40%) who are possible implantable cardioverter-defibrillator (ICD) candidates should undergo re-evaluation of LVEF ≥40 days after discharge (Class I, LOE: B). If the LVEF remains ≤35% with symptoms (or ≤30% without symptoms), an ICD is recommended (49). The ESC makes a similar recommendation with an even stronger level of evidence (Class I, LOE: A). However, in the text, the ESC suggests postponing re-evaluation of left ventricular function until 3 months after revascularization procedures to allow adequate time for recovery of LV function.
Considerations for Future Guidelines
With the evolving progress in STEMI care, subsequent iterations of guideline recommendations require incorporation of the most contemporary evidence-based studies. For instance, the optimal reperfusion strategy for early presenters with STEMI has been recently informed by the STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial supporting early fibrinolysis as a legitimate alternative to primary PCI in patients who cannot undergo timely intervention (50). Moreover, an additional pre-specified STREAM analysis, stratified by delays in primary PCI, indicates similarity between an early fibrinolysis approach and primary PCI at 50 to 60 min, but superiority over primary PCI emerged if the PCI-related delay extended beyond 90 min (51). Hence, the optimal time for “PCI-related delay” deserves re-evaluation.
Regarding optimal anticoagulant pharmacotherapy in primary PCI, the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial randomizing primary PCI patients to pre-hospital bivalirudin or heparin (roughly 40% did not receive a GP IIb/IIIa antagonist) found no difference in 30-day death with bivalirudin (although bleeding was reduced). However, safety concerns were conveyed, given the higher risk of acute stent thrombosis seen in patients treated with bivalirudin (52). More recently, the HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention) trial of primary PCI patients randomized to heparin versus bivalirudin (balanced use of GP IIb/IIIa antagonists) found a higher risk of major adverse events with bivalirudin, with no reduction in bleeding. Furthermore, a higher incidence of stent thrombosis was noted (53). Hence, in contemporary practice with more potent P2Y12 receptor agents (hence lower GP IIb/IIIa inhibitor use), bivalirudin use will warrant re-evaluation in the future.
Recommendations for radial access site in STEMI may also garner strengthened support in future guidelines. Since publication of the guidelines, a multitude of randomized studies have attempted to address the benefits of radial versus femoral access in ACS. The latest MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial of ACS patients found improvements in clinical outcomes with radial access and a lower rate of major bleeding at 30 days. Furthermore, all-cause mortality was reduced with the radial access approach (54). The MATRIX authors also performed a meta-analysis of MATRIX (54), RIVAL (21), RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) (55), and STEMI-RADIAL (ST Elevation Myocardial Infarction treated by RADIAL or femoral approach) (56), showing a reduction in death and non–coronary artery bypass graft major bleeding with radial cardiac catheterization (54).
Most recently, the recommendations on performing nonculprit intervention have been challenged by new randomized studies of modest size supporting routine complete revascularization with PCI in STEMI patients with multivessel disease during the index cardiac catheterization (PRAMI [Preventive Angioplasty in Acute Myocardial Infarction] , CVLPRIT [Complete Versus culprit-Lesion only PRimary PCI Trial] ) or as a staged PCI (DANAMI [DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction]-3 and PRIMULTI [Primary PCI in Patients With ST-elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization] ). The large, well-powered, ongoing, international, multicenter COMPLETE (Complete versus Culprit-only Revascularization to Treat Multi-vessel Disease after Primary PCI for STEMI) trial is expected to definitively address the optimal revascularization strategy in STEMI patients with multivessel disease undergoing primary PCI (60). Finally, both sets of guideline recommendations list aspiration thrombectomy in STEMI as Class IIa, LOE: B. However, the results of the TASTE (Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia) (61) and TOTAL (Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI) (62) studies have challenged the utility of routine aspiration in STEMI, showing no benefits in clinical outcomes (including survival), with the possibility of harm (increased risk of stroke seen in TOTAL ). This recommendation has now been downgraded by the ACC/AHA/SCAI 2015 focused update to Class III, LOE: A for routine aspiration and to Class IIb, LOE: C as a bailout procedure (6).
It appears that legitimate reasons exist for both the ACCF/AHA and the ESC to maintain separate guidelines for STEMI, given their different target audiences, available medicines, and resources (64). However, alignment on levels of evidence from the same sources seems desirable, and may even be facilitated by the recent move of the ACCF/AHA toward engaging a separate evidence review committee comprised of methodologists, epidemiologists, and biostatisticians (65). This process would be clearly enhanced by an appropriately constituted single group derived from both sides of the Atlantic that facilitate optimizing STEMI networks and care (66). The continuing escalation in health care costs will preclude or substantially inhibit the introduction of certain novel therapies in some countries and regions. Hence, the introduction of an economic-based, return-on-investment framework that helps to address the potential cost-effectiveness of the recommendations would be welcome. Finally, harnessing the power of electronic media to bring these elements together nimbly at the patient-provider interface shows great promise in ensuring knowledgeable application of guidelines by practitioners at the clinical interface.
Dr. Armstrong has served as a consultant to AstraZeneca, Axio/Orexigen, Merck, Eli Lilly, and Bayer; and has received grants/contracts from Amylin Pharmaceuticals Inc., Sanofi, F. Hoffmann-La Roche Ltd., and Merck. Dr. Bainey has reported that he has no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American College of Cardiology Foundation
- acute coronary syndromes
- American Heart Association
- dual antiplatelet therapy
- European Society of Cardiology
- first medical contact
- level of evidence
- myocardial infarction
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- unfractionated heparin
- Received August 26, 2015.
- Revision received November 5, 2015.
- Accepted November 6, 2015.
- 2016 American College of Cardiology Foundation
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