Updated Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) ST-Segment Elevation Myocardial Infarction Critical Pathway Toolkit

The Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) acute coronary syndromes critical pathway toolkit has been revised again based on the 2007 focused update of the American College of Cardiology/American Heart (ACC/AHA) Association guidelines for the management of patients with ST-segment elevation myocardial infarction (STEMI). A previous update of the toolkit incorporated the 2007 ACC/AHA guidelines for unstable angina/non-ST-segment elevation myocardial infarction. This review highlights the major revisions to the STEMI guidelines, and illustrates and describes the revised STRIVE critical pathway tools for STEMI, which include pathway flowcharts, standing orders, pocket cards, and posters. The updated STEMI tools are available to clinicians online on the STRIVE Website.

Acute coronary syndromes (ACS) represent a spectrum of clinical presentations ranging from unstable angina (UA) through non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI).^1-3 STEMI is characterized by complete occlusion of the coronary artery, whereas NSTEMI is distinguished by subtotal, but nevertheless severe, occlusion.^3,4 In 2005, the number of unique hospital discharges for ACS was estimated at 1.4 million.⁵ Assuming that STEMI patients account for 29%,⁶ approximately one-third of ACS discharges per year were for STEMI.⁵

In an effort to respond quickly to new evidence from clinical trials on the management of patients with STEMI, in December 2007 the American College of Cardiology/American Heart Association (ACC/AHA) published an update to their 2004 guidelines on the management of acute STEMI.⁷ The STEMI guideline update incorporates new recommendations on antithrombotic therapy, percutaneous coronary intervention (PCI), and thrombolysis, and puts new emphasis on the integration of STEMI systems of care, from triage in the field and initial management in the emergency department through community hospital and interhospital transport to the PCI-capable hospital and the catheterization laboratory. The 2004 ACC/AHA STEMI guidelines⁸ should be consulted for policy on clinical areas not covered by the focused update.

The Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) ACS critical pathway toolkit, which was revised previously based on the ACC/AHA 2007 guidelines for the management of patients with UA/NSTEMI⁹ and outlined in a recent article,¹⁰ was updated again recently to include revisions based on the 2007 ACC/AHA focused update on the management of patients with STEMI.⁷ The STRIVE education initiative regularly updates clinicians on the latest developments in cardiology and provides the tools and techniques (through critical pathways) to apply evidence-based medicine in daily practice. The content for STRIVE activities, including the critical pathway toolkit items, is developed by the healthcare professionals who serve on the STRIVE Scientific Committee (see Appendix). The toolkit is available for downloading on the STRIVE Website at http://www.strivecme.com/index.asp?nav=CriticalPathways.asp. Critical pathway tools, such as the STEMI tools illustrated here (Figs. 1-6), can be used to remind busy clinicians of the various guideline-recommended therapies that must be administered to a patient with acute MI.¹¹

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Figure 6

Overview of the ACC/AHA 2007 Focused Update on the Management of Patients With STEMI

Management of patients with STEMI requires a team effort that begins in the field and continues with initial presentation in the emergency department through management in the community hospital or PCI facility. The goal of therapy-restoring blood flow to the obstructed artery-is the same, whether fibrinolysis or PCI is used. The choice of which approach to implement is also based on practical considerations, such as transport time and receiving hospital capabilities (Fig. 1).

Prehospital emergency medical systems (EMS) providers should administer aspirin (chewed) to chest pain patients suspected of having STEMI, unless contraindicated or already taken by the patient.⁸ When possible, EMS should obtain a 12-lead electrocardiogram before the patient arrives at the hospital.⁷ If EMS has fibrinolytic capability and the patient qualifies for therapy (Fig. 2), prehospital fibrinolysis should be started within 30 minutes of arrival of EMS on the scene.⁸

Rapid Reperfusion Therapy: Fibrinolysis or PCI?

The updated STEMI guidelines strengthen the emphasis on reducing the time to reperfusion, achieved preferably with PCI rather than fibrinolysis if a skilled PCI laboratory is available, either onsite or offsite, within 90 minutes of patient presentation.⁷ PCI also is the preferred approach in settings where the risk of death is increased due to cardiogenic shock, fibrinolysis is contraindicated due to an increased risk of bleeding and intracranial hemorrhage, the onset of MI was greater than 3 hours, or the diagnosis of STEMI is unclear (Fig. 1).⁸ If PCI is not available within 90 minutes, fibrinolytic therapy should be initiated within 30 minutes of hospital presentation, unless contraindicated (Fig. 3).⁸ Systems that are able to achieve even more rapid times for treatment of patients with STEMI should be encouraged.⁷

Rescue PCI and Facilitated PCI

For patients who have failed to achieve sufficient reperfusion with thrombolytics, transfer protocols need to be in place for arranging for rescue PCI. In a recent meta-analysis, rescue PCI was associated with a significant relative risk reduction of 28% compared with medical therapy.¹² Rescue PCI or emergency coronary artery bypass grafting is recommended for cardiogenic shock in patients younger than 75 years, severe congestive heart failure and/or pulmonary edema, or hemodynamically compromising ventricular arrhythmias.⁷

Facilitated PCI, a strategy of planned immediate PCI after reduced-dose thrombolytic therapy, is not recommended as a routine strategy.⁷ The Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) trial showed that the primary end point (a composite of death, shock, and congestive heart failure within 90 days) was significantly higher in patients assigned to facilitated PCI compared with primary PCI (19% vs. 13%; P = 0.0045).¹³ Although using full-dose thrombolytics in facilitated PCI may be harmful, using regimens other than full-dose fibrinolytic therapy may be considered for restoring blood flow when all of the following are present: the patient is at high risk, PCI is not immediately available within 90 minutes, and the bleeding risk is low.⁷

Acute Medical Therapy

Acute medical treatment of STEMI, documented in tools such as standing orders (Fig. 4), includes morphine, nitrates, oxygen, and aspirin.^7,8 Patients routinely taking nonsteroidal anti-inflammatory drugs (NSAIDs), except for aspirin, both nonselective- and cyclooxgenase-2 (COX-2)-selective agents, before STEMI should have those agents discontinued at the time of presentation with STEMI because of the increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use.⁷

Oral β-blocker therapy should be initiated within the first 24 hours for STEMI patients who do not have signs of heart failure, evidence of a low output state, an increased risk for cardiogenic shock, or other relative contraindications to β-blockade.⁷ Intravenous β-blockers should be avoided in patients with these risk factors.

Anticoagulant Therapy

A significant change in the 2007 STEMI focused update surrounds the use of anticoagulation, in that not all STEMI patients have a Class I recommendation to receive an anticoagulant (barring any contraindications). There are several anticoagulants from which to choose, including unfractionated heparin (UFH), enoxaparin, and fondaparinux, administered as specified in the guidelines⁷ (also see Fig. 4). Bivalirudin may be used in patients treated previously with UFH. Fondaparinux should not be used as the sole anticoagulant to support PCI, because of the risk of catheter thrombosis; an additional anticoagulant with anti-IIa activity should be administered.⁷ Patients who received upstream UFH or enoxaparin can continue to use those agents when moving to PCI after fibrinolytic therapy. The recommended time period is at least 48 hours and preferably for the duration of the index hospitalization, up to 8 days, for patients undergoing reperfusion with fibrinolytics. Regimens other than UFH are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of heparin-induced thrombocytopenia with prolonged UFH treatment. These subcutaneous regimens are also recommended for patients not receiving reperfusion therapy.

The updated recommendations for anticoagulant therapy were based on results of the Enoxaparin and Thrombolysis for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction 25 (ExTRACT-TIMI 25)¹⁴ and Organization for the Assessment of Strategies for Ischemic Syndromes (OASIS-6)¹⁵ trials. The ExTRACT-TIMI 25 trial found a highly significant (P <0.001) 17% reduction in the relative risk of death or nonfatal recurrent MI in STEMI patients at 30 days with enoxaparin versus UFH.¹⁴ In OASIS-6, the primary end point (the composite of death or reinfarction at 30 days) was reduced from 11.2% in the control group (either placebo or UFH) to 9.7% in the fondaparinux group (P = 0.008).¹⁵ In the subgroup of patients undergoing primary PCI (during which intravenous heparin was used in all patients in the control group and in only 21% in the fondaparinux group), there was a trend toward harm in patients receiving fondaparinux compared with those in the control group (6.0% vs. 4.9%, respectively; P = 0.04). In addition, guiding catheter thrombosis occurred more often in the fondaparinux group compared with the control group (22 vs. 0 patients, respectively; P <0.001).¹⁵

Antiplatelet Therapy

The 2007 STEMI focused update recommends the addition of clopidogrel 75 mg per day orally to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy.⁷ Clopidogrel treatment should continue for at least 14 days.

Evidence for the benefit of adding clopidogrel to aspirin in patients undergoing fibrinolysis was provided by the results of the Clopidogrel and Metoprolol in Myocardial Infarction Trial/Second Chinese Cardiac Study (COMMIT/CCS-2)¹⁶ and Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28).¹⁷ COMMIT/CCS-2 also supported the use of clopidogrel in patients not undergoing fibrinolysis.¹⁶ In COMMIT/CCS-2,¹⁶ allocation to clopidogrel produced a 9% reduction (P = 0.002) in death, reinfarction, or stroke. Predischarge deaths were reduced by 7% (P = 0.03) in the clopidogrel group. In CLARITY-TIMI 28,¹⁷ the occurrence of the primary end point of occluded artery, death, or MI was reduced by 36% when clopidogrel was added. There was a 20% reduction in the clinical end points of cardiovascular death, MI, or recurrent ischemia leading to the need for urgent revascularization, which was noted early on and continued through the 30-day time period. In both trials, the benefits of clopidogrel were not associated with an increased risk of major bleeding or intracranial hemorrhage.

In patients younger than 75 years of age who receive fibrinolytic therapy or who do not receive reperfusion therapy, it is reasonable to administer an oral loading dose of clopidogrel 300 mg.⁷ (No data are available to guide decision making regarding an oral loading dose in patients 75 years of age or older.)

According to the 2007 focused update of the ACC/AHA/Society for Cardiovascular Angiography and Interventions (SCAI) 2005 guideline update for PCI,¹⁸ a loading dose of clopidogrel, generally 600 mg, should be administered before or when PCI is performed. In patients undergoing PCI within 12 to 24 hours of receiving fibrinolytic therapy, a clopidogrel oral loading dose of 300 mg may be considered. If clopidogrel is given at the time of the procedure, supplementation with glycoprotein IIb/IIIa inhibitors may be beneficial.

Long-Term Antiplatelet and Anticoagulant Therapy

For all patients, aspirin 75 to 162 mg per day should be prescribed indefinitely.⁷ For aspirin-allergic patients, clopidogrel alone should be prescribed indefinitely or aspirin desensitization can be tried. Clopidogrel 75 mg per day should be prescribed for at least 14 days. Long-term maintenance therapy (eg, 1 year) with clopidogrel (75 mg per day orally) is reasonable in STEMI patients regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy.⁷

Recommendations for long-term antiplatelet and anticoagulant therapy for patients treated with bare-metal stents (BMS) or drug-eluting stents (DES) are shown in Figure 5. The recently updated guidelines for both STEMI⁷ and UA/NSTEMI⁹ underscore the importance of preventing premature discontinuation of antiplatelet therapy in patients receiving coronary artery stents (Fig. 6). For patients treated with BMS, aspirin 162 to 325 mg per day should be prescribed for at least 1 month, then continued indefinitely at a dose of 75 to 162 mg per day.⁷ Clopidogrel 75 mg per day should be prescribed for a minimum of 1 month and ideally for up to 1 year in patients receiving BMS, unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks. For patients treated with DES, aspirin 162 to 325 mg per day should be prescribed for at least 3 months after sirolimus-eluting stent implantation and 6 months after paclitaxel-eluting stent implantation, then continued indefinitely at a dose of 75 to 162 mg per day.⁷ Clopidogrel 75 mg daily should be given for at least 12 months to all post-PCI patients receiving DES.

Managing warfarin to an international normalized ratio (INR) equal to 2.0 to 3.0 for paroxysmal or chronic atrial fibrillation or flutter is recommended, and in post-MI patients when clinically indicated (eg, atrial fibrillation, left ventricular thrombus).⁷ Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely. In patients requiring warfarin, clopidogrel, and aspirin therapy, an INR of 2.0 to 2.5 is recommended with low-dose aspirin (75-81 mg) and a 75-mg dose of clopidogrel.

Drug-Eluting Stents Versus BMS

On December 7 and 8, 2006, the US Food and Drug Administration convened a meeting of its Circulatory System Devices Advisory Panel to discuss stent thrombosis and the overall safety of DES.¹⁹ According to the panel, safety concerns do not outweigh the benefits of DES compared with BMS when used within the limits of the approved labeling (Fig. 6).²⁰ The advisory panel concurred with the ACC/AHA/SCAI 2005 joint clinical practice guideline recommendation on the importance of 12 months of dual antiplatelet therapy after placement of a DES in patients who are not at high risk of bleeding and educating the patient and healthcare providers about the hazards of premature discontinuation.¹⁹ However, they agreed that a large randomized trial looking specifically at the appropriate duration of dual antiplatelet therapy is needed.

Secondary Prevention

New secondary prevention measures focus on smoking cessation, use of lipid-lowering therapies, and avoidance of NSAIDs.⁷ The 2007 goal for smoking is complete cessation and no exposure to environmental tobacco smoke.

Statins, in the absence of contraindications, regardless of baseline low-density lipoprotein cholesterol (LDL-C) and diet modification, should be given to post-STEMI patients, including postrevascularization patients.⁷ For hospitalized patients, lipid-lowering medications should be initiated before discharge. For STEMI patients with LDL-C ≥100 mg per dL, cholesterol-lowering therapy should be initiated or intensified to achieve an LDL-C of <100 mg per dL. Further titration to <70 mg per dL is reasonable. Adding plant stanol/sterols (2 g per day) and/or viscous fiber (>10 g per day) is reasonable to further lower LDL-C. If triglycerides are 200 mg per dL or higher, non-high-density lipoprotein cholesterol should be less than 130 mg per dL.

Use of NSAIDs with high selectivity for COX-2 should be avoided.⁷ A stepped-care approach to pharmacological management of musculoskeletal symptoms should be used. Pain relief should begin with acetaminophen or aspirin, low-dose narcotics, or nonacetylated salicylates.

Other changes to the previous STEMI guidelines include the addition of recommended daily physical activity and a new recommendation for an annual influenza vaccination.⁷

Summary of 2007 STEMI Focused Update

Highlights of the ACC/AHA 2007 STEMI focused update⁷ include the following:

* Initiation of oral β-blocker therapy within the first 24 hours for patients without signs of heart failure and other contraindications.

* Primary PCI within 90 minutes of first medical contact.

* Fibrinolytic therapy within 30 minutes of first medical contact for patients presenting to a hospital without PCI capability and who cannot be transferred to a PCI center and undergo PCI within 90 minutes.

* A strategy of coronary angiography with intent to perform PCI (or emergency coronary artery bypass grafting) for patients who received fibrinolytic therapy and have cardiogenic shock (patients <75 years who are suitable candidates for revascularization), severe congestive heart failure and/or pulmonary rales, or hemodynamically compromising ventricular arrhythmias.

* Discontinuation of NSAIDs at time of presentation.

* Anticoagulant therapy for a minimum of 48 hours (and preferably for the duration of the index hospitalization, up to 8 days) for patients undergoing reperfusion with fibrinolytics. Regimens other than UFH are recommended if anticoagulant therapy is given for more than 48 hours. It is reasonable to use this same approach for nonreperfused patients.

* Clopidogrel 75 mg per day orally, for at least 14 days, added to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy.

* Long-term maintenance therapy (eg, 1 year) with clopidogrel (75 mg per day orally) is reasonable in STEMI patients regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy.

* Advising every tobacco user (and family members who smoke) to quit.

* For all post-PCI stented patients with STEMI, aspirin at a dose of 162 to 325 mg daily for at least 1 month after BMS implantation, 3 months after sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, after which long-term aspirin use is continued indefinitely at a dose of 75 to 162 mg daily.

* For all post-PCI patients who receive a DES, clopidogrel 75 mg daily for at least 12 months; for post-PCI patients who receive a BMS, clopidogrel for a minimum of 1 month, and ideally up to 12 months. If the patient is at increased risk of bleeding, then it should be given for a minimum of 2 weeks.

* For all post-STEMI patients, statins (in the absence of contraindications) regardless of baseline LDL-C and diet modification. For hospitalized patients, lipid-lowering medications should be initiated before discharge.

Critical Pathways and Quality Improvement Initiatives

Critical pathways are developed to ensure that current practice guidelines are instituted and followed. Implementing guideline-based critical pathways can improve quality-of-care measures such as door-to-drug and door-to-balloon (D2B) times, optimize patient triage, prevent underutilization of recommended medications, ensure appropriate use of proven medications and treatments, facilitate communication between specialist physicians and primary care physicians during hospitalization and after discharge, enhance patient compliance and outcomes, reduce the potential for medical errors, reduce costs by limiting length of stay and unnecessary tests, and improve compliance with national standards (such as those of the Joint Commission).¹¹

Quality improvement initiatives such as the AHA's Mission Lifeline program²¹ and the ACC's D2B: An Alliance for Quality campaign²² also aim to improve the quality of care of patients with STEMI. The goal of the D2B campaign is to achieve a D2B time of ≤90 minutes for at least 75% of nontransfer primary PCI patients with STEMI in all participating hospitals performing primary PCI.²²

ACTION Registry-GWTG, the result of a collaboration between the NCDR ACTION Registry and the AHA Get With The Guidelines-CAD Registry, provides healthcare professionals and their facilities with the information needed to monitor and improve adherence to guidelines, including measurement of average D2B time.²³ Results from a recent study show that median D2B times in STEMI patients eligible for primary PCI have improved modestly over the last few years in hospitals participating in the Get With The Guidelines program but remain below ideal levels.²⁴ The overall median D2B time for the participating sites for the period 2002 through 2006 was 96 minutes (interquartile range, 69-140 minutes), although median D2B time did improve over the study period. Only 44.8% of cases had D2B times ≤90 minutes. D2B times were particularly delayed in the elderly, women, and minority populations.

A multivariate analysis identified 6 strategies that were significantly associated with a faster D2B time²⁵:

* Having emergency medicine physicians activate the catheterization laboratory.

* Having a single call to a central page operator activate the catheterization laboratory.

* Having the ED activate the catheterization laboratory while the patient is still en route.

* Expecting staff to arrive at the catheterization laboratory within 20 minutes after the page.

* Having an attending cardiologist always on site.

* Having staff in the ED and catheterization laboratory use and receive real-time feedback.

However, despite the effectiveness of the strategies, only a minority of hospitals surveyed used them.

Fox and colleagues²⁶ analyzed data from 44,372 patients who were enrolled in the Global Registry of Acute Coronary Events (GRACE) and followed up for approximately 6 months after discharge. Improvements in the management of patients with ACS were associated with significant reductions in the rates of new heart failure and mortality and in rates of stroke and MI at 6 months. Use of Class I, level of evidence A, recommended medications for STEMI increased over the study period, as did use of other guideline-indicated medications.

Critical pathway programs such as STRIVE, data registries such as GRACE and ACTION Registry-GWTG, and quality improvement initiatives such as Mission Lifeline and D2B: An Alliance for Quality are ongoing efforts to help improve the quality of care for patients with STEMI.

CONCLUSIONS

To keep clinicians up-to-date with new data from clinical trials, clinical practice guidelines for ACS are updated regularly. For patients with STEMI, timeliness of reperfusion treatment and use of guideline-recommended therapies are of critical importance. Critical pathways are developed to promote adherence to current practice guidelines and accepted standards of care. Implementation of guideline-based critical pathways has been shown to improve quality of care and patient outcomes. The STRIVE implementation toolkit items, available for downloading free of charge on the STRIVE Website, can help hospital teams implement effective, evidence-based critical pathways for ACS.