ST-segment elevation myocardial infarction (STEMI) is a significant health problem in industrialized countries and is becoming an increasingly significant problem in developing countries. STEMI is a clinical syndrome defined by characteristic symptoms of myocardial ischemia in association with electrocardiographic (ECG) ST-segment changes (usually elevation) indicative of the occlusion of a major epicardial coronary artery. The incidence of STEMI varies according to the database examined ( Table 10-1 ). STEMI comprised approximately 40% of all MI presentations in the first two quarters of 2009 at hospitals participating in the Acute Coronary Treatment and Intervention Outcomes Network Registry (ACTION)–Get With the Guidelines (GWTG). One third of patients will die within the first 24 hours of presentation, many by sudden death. In the past few decades, the mortality rate from STEMI has steadily declined, but the rate of decline appears to have slowed. This appears to be due to both a fall in the incidence of STEMI and a reduction in the case fatality rate. A significant increase in the use of evidence-based treatments from 1996 to 2007 in the Swedish registry of 61,238 patients with STEMI was associated with significantly improved in-hospital, 30-day, and 1-year mortality rates that was maintained after multivariate adjustment. A progressive increase in the proportion of patients who present with non-STEMI has also occurred. This chapter follows the clinical course of the STEMI patient from before STEMI to management in the prehospital setting, the emergency department (ED), the hospital, and after hospital discharge.
|MI REGISTRY||% STEMI|
|National Registry of Myocardial Infarction (NRMI-4)||29%|
|AHA Get with the Guidelines||32%|
|Global Registry of Acute Coronary Events (GRACE)||38%|
Pre–ST-Segment Elevation Myocardial Infarction Management
Primary and secondary prevention interventions aimed at the risk factors associated with coronary heart disease (CHD) reduce the risk of STEMI. These include smoking cessation, diet, exercise, lipid management, blood pressure (BP) control, and diabetes management. Primary care providers should evaluate the presence and control of major risk factors in each patient every 3 to 5 years. The 10-year risk of developing symptomatic CHD should be calculated for all patients who have two or more major risk factors to assess the need for primary prevention strategies. Patients with established CHD should be identified for secondary prevention, and patients with a CHD risk equivalent (e.g., diabetes mellitus, chronic kidney disease, peripheral vascular disease, 10-year risk >20% as calculated by the Framingham equations) should receive equally intensive risk factor intervention as those with clinically apparent CHD.
Morbidity and mortality from STEMI can be reduced if patients and bystanders are taught to recognize symptoms early and activate emergency medical services (EMS). Patients with symptoms of STEMI should be transported to the nearest appropriate hospital by ambulance so they can receive cardiopulmonary resuscitation (CPR) and defibrillation, if necessary, as well as early reperfusion therapy. One in every 300 patients with chest pain transported to the ED by private vehicle goes into cardiac arrest en route.
Although the traditional recommendation is for patients to take one sublingual nitroglycerin dose up to three doses, 5 minutes apart, before calling EMS, this recommendation has been modified to encourage earlier EMS contact. If symptoms suggestive of STEMI are unimproved or worsen 5 minutes after one nitroglycerin dose, patients should immediately call 911.
Early recognition of symptoms is the first step in the Chain of Survival. Although most people recognize chest pain as a presenting symptom of STEMI, many are unaware of associated symptoms, such as arm pain, lower jaw pain, shortness of breath, and diaphoresis or anginal equivalents. For a variety of reasons, the average patient does not seek medical attention for at least 1.5 hours after symptom onset. Longer delay times occur among non-Hispanic blacks, older patients, Medicaid patients, and women. Fully one third of patients with confirmed STEMI may present to the hospital with symptoms other than chest discomfort, and as many as half of all STEMI events are clinically silent or unrecognized by the patient. A high index of suspicion for STEMI should be maintained when evaluating women, diabetics, older patients, and those with a history of heart failure, as well as patients complaining of chest discomfort but who have a permanent pacemaker or bundle branch block that may confound the recognition of STEMI on ECG.
The majority of deaths from STEMI occur in the first 1 to 2 hours after symptom onset, usually from ventricular fibrillation (VF). Every minute the patient spends in VF decreases the chance of survival by 7% to 10%. Key elements of the Chain of Survival include early activation of the EMS system, early CPR and defibrillation for those who need it, and advanced cardiac life support protocols. Survival was doubled in the National Institutes of Health sponsored Public Access Defibrillation (PAD) trial by training lay volunteers to use an automatic external defibrillator (AED) in high-risk public settings. Largely through the educational initiatives of the American Heart Association (AHA), 60% of Americans say they are familiar with CPR, 98% understand what an AED does, and 31.4% of out-of-hospital cardiac arrests receive bystander CPR. With this in mind, family members of STEMI patients should be advised to take CPR and AED training. Because of the high prevalence of acute coronary artery occlusion in out-of-hospital cardiac arrest patients who are successfully resuscitated, especially those whose initial rhythm is VF in the setting of STEMI, the AHA 2010 CPR/emergency cardiovascular care guideline recommends emergent coronary angiography with prompt primary percutaneous coronary intervention (PCI). Therapeutic hypothermia should be started as soon as possible in patients with STEMI and anoxic encephalopathy who survive out-of-hospital cardiac arrest.
Emergency Medical Services and Systems of Care
The AHA and the American College of Cardiology (ACC) have worked together to promote systems of care for STEMI patients. The AHA “Mission Lifeline” program recommendations include a multifaceted community-wide approach involving patient education, improvements in EMS and ED care, establishment of networks of referral (non-PCI capable) and receiving (PCI capable) hospitals, and coordinated advocacy efforts to work with payers and policymakers to implement these changes. Information about the initiative is available at the AHA website ( www.americanheart.org ). In 2006, the ACC launched its Door-to-Balloon (D2B; www.d2b.acc.org ) and ACTION-GWTG registry through the National Cardiovascular Data Registry to help participating hospitals reach the recommended time for primary PCI (P-PCI) within 90 minutes of first medical contact and implement guideline-recommended therapies. In addition, the American College of Cardiology Foundation (ACCF)/AHA Task Force for Practice Guidelines and the ACC/AHA Performance Measures have updated clinical practice guidelines and quality metrics. It is now recommended that each community develop a STEMI system of care that includes prehospital identification of STEMI patients and catheterization laboratory activation, destination protocols for STEMI receiving centers, and transfer protocols for high-risk STEMI patients who are P-PCI candidates, are fibrinolytic ineligible, or are in cardiogenic shock. To minimize time to treatment, particularly for cardiopulmonary arrest, many communities allow volunteers and/or firefighters and other first-aid providers to function as first responders, providing CPR and early defibrillation with an AED until EMS arrives. The EMS ambulance response is a tiered system. The basic EMT level includes first aid and early defibrillation with AEDs. Other units are staffed by paramedics or other intermediate-level EMTs who can give basic care, start intravenous (IV) lines, intubate, and administer medications. In some systems, the advanced providers can also perform a 12-lead ECG, provide external pacing for symptomatic bradycardia, and use other techniques. Some high-performance EMS systems have only advanced life support–staffed ambulances.
Prehospital EMS providers should administer 162 to 325 mg of chewable aspirin, unless contraindicated, to patients suspected to be having an STEMI. The use of 12-lead ECGs by paramedics to evaluate all patients with possible ischemic chest discomfort in the prehospital setting is strongly encouraged. For patients with ECG evidence for STEMI, a reperfusion checklist may be relayed along with the ECG to a predetermined medical control facility or hospital.
Randomized, controlled trials have demonstrated the benefit of initiating fibrinolytic therapy as early as possible after the onset of STEMI. Prehospital administration allows half of patients to be treated within 2 hours of symptom onset, when the greatest treatment benefit can be expected. A French national registry has demonstrated lower 1-year mortality rates with prehospital fibrinolytic therapy than with in-hospital fibrinolysis or P-PCI ( Figure 10-1 ). However, a prehospital fibrinolytic program requires either a physician in the ambulance or a highly organized program with well-trained paramedics who can transmit the ECG to a medical command center with a medical director.
Prehospital Destination Protocols
Every community should have a written protocol that guides EMS personnel in determining where to take patients with suspected or confirmed STEMI ( Figure 10-2 ). In general, patients with suspected STEMI should be taken to the nearest PCI-capable hospital if the anticipated first medical contact to balloon or device time is within 90 minutes. Patients with STEMI who present to, or are transported to, hospitals without PCI capability should be transported secondarily to a PCI-capable hospital if the anticipated first medical contact to balloon or device time is less that 120 minutes, especially patients with high-risk features who are candidates for P-PCI. For patients presenting to a hospital without PCI capability, if the first medical contact to device time is anticipated to be greater than 120 minutes and there are no contraindications, fibrinolysis should be administered within 30 minutes of first medical contact. Secondary transport to a PCI-capable hospital—urgently after fibrinolysis for evidence of reperfusion failure or reocclusion or within 3 to 24 hours as part of an invasive strategy—can then occur.
Emergency Department Management
The effectiveness of a variety of treatment options diminishes rapidly within the first several hours after symptom onset, so rapid triage is important. The traditional ED evaluation of patients with chest pain relies heavily on the patient’s history, physical examination, and ECG. All patients presenting to the ED with chest discomfort or other symptoms suggestive of STEMI should immediately be placed on a cardiac monitor with emergency resuscitation equipment nearby, including a defibrillator. An IV line should be started for rapid delivery of medications. An ECG should be performed and shown to an experienced emergency medicine physician within 10 minutes of ED arrival if one has not already been sent from the ambulance. Advanced directives should be clarified, especially in elderly patients, to prevent treatment contrary to the patient’s wishes. If STEMI is present, the decision whether the patient will be treated with fibrinolytic therapy or P-PCI should be made within the next 10 minutes. The goal should be to achieve a door-to-needle time within 30 minutes or a door-to-balloon time within 90 minutes, or interhospital transport with first medical contact to device time less that 120 minutes. If the initial ECG is not diagnostic, the patient remains symptomatic, and there is a high clinical suspicion for STEMI, serial ECGs at 5- to 10-minute intervals or continuous ST-segment monitoring should be performed. The choice of initial STEMI treatment should be made by the emergency medicine physician based on a predetermined, institution-specific, written protocol. If the initial diagnosis and treatment plan are not clear, immediate cardiology consultation should be obtained.
A targeted history should ascertain whether the patient has had prior stable or unstable angina, MI, coronary artery bypass graft (CABG) surgery, or PCI. Evaluation of the patient’s symptoms should focus on chest discomfort, associated symptoms, sex- and age-related differences in presentation, hypertension, diabetes mellitus, possibility of aortic dissection, risk of bleeding, and clinical cerebrovascular disease (e.g., amaurosis fugax, facial/limb weakness or clumsiness, sensory loss, ataxia, or vertigo). A brief targeted physical examination should focus on potential complications of STEMI, such as CHF, cardiogenic shock, ventricular septal defect (VSD), or ischemic mitral regurgitation (MR). A differential diagnosis should be reviewed to exclude other conditions that may mimic STEMI, such as aortic dissection, pulmonary embolism, pericarditis, or cocaine ingestion.
The 12-lead ECG in the ED is at the center of the therapeutic decision pathway. The risk of death increases with the number of ECG leads that show ST-segment elevation, the sum of ST-segment deviation in 12 leads, and the presence of Q waves on presentation. Important predictors of death include anterior location and left bundle branch block (LBBB). Patients with inferior STEMI should have right-sided leads obtained to screen for ST elevation suggestive of right ventricular (RV) infarction. Although patients without ST elevation should not be treated with fibrinolytic therapy, it may be used appropriately when there is marked ST-segment depression confined to leads V1 through V4 and accompanied by tall R waves in the right precordial leads and upright T waves indicative of a true posterior injury current. Patients with new or presumed new LBBB and signs and symptoms of STEMI should also be considered for reperfusion therapy. LBBB with concordant ST-segment elevation of 0.1 mV or greater toward the major QRS deflection in at least one lead, or concordant ST-segment depression (with a dominant S wave) of 0.1 mV or greater in anterior precordial leads V1, V2, or V3, or discordant ST-segment elevation of 0.5 mV or greater in leads with a negative QRS suggest STEMI. ST-segment elevation in lead aVR or V1 of 0.1 mV or greater when accompanied by ST-segment depression of 0.1 mV or greater in eight or more leads may indicate left main or multivessel obstruction. ECG abnormalities that may mimic STEMI, such as hyperkalemia, pericarditis, acute cerebral hemorrhage, Brugada syndrome, left ventricular (LV) hypertrophy, tako-tsubo syndrome, Prinzmetal angina, or cocaine ingestion should be distinguished from STEMI by ECG changes, history, and physical examination.
Laboratory measurements should include serial cardiac biomarkers (MB fraction of creatine kinase [CK-MB], troponins) for cardiac damage, complete blood count, platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), electrolytes, magnesium, blood urea nitrogen, creatinine, glucose, and serum lipids. Therapeutic decisions should not be delayed until these results are returned. Cardiac biomarkers are useful for confirming the diagnosis of STEMI, assessing the success of fibrinolytic therapy, estimating infarct size, and providing prognostic information.
Several imaging tests can be used to evaluate chest pain. Portable chest radiography should be performed but should not delay initiation of reperfusion therapy. Transthoracic and/or transesophageal echocardiography is quite useful for evaluating ventricular function and diagnosing mechanical complications. Contrast chest computed tomography (CT) may be required to exclude aortic dissection. CT angiography and magnetic resonance imaging are not indicated in patients with suspected STEMI. Radionuclide imaging is not indicated in the acute setting.
Early Risk Assessment
Assessing global risk allows the physician to integrate patient-specific characteristics into a semiquantitative score that can provide an estimate of a patient’s prognosis, dictate the acuity and intensity of care needed, and triage to the appropriate location of care. Some examples of independent predictors for early death from STEMI include advanced age, higher Killip class, cardiac arrest, tachycardia, hypotension, anterior infarct location, prior infarction, diabetes, renal insufficiency, and positive initial cardiac markers and Q waves. The Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI ( www.mdcalc.com/timi-risk-score-for-stemi ) uses a combined clinical endpoint that includes death, stroke, and recurrent ischemia. Risk assessment should be a continuous process, repeated throughout the index hospitalization.
Medications Used in the Acute Phase
Supplemental oxygen is appropriate for patients with STEMI who are hypoxemic (oxygen saturation <90%) and may have a salutary, albeit placebo, effect in others. In patients with severe CHF, pulmonary edema, or mechanical complications, endotracheal intubation and mechanical ventilation may be required.
Nitrates are indicated to relieve ischemic pain and control hypertension and as a vasodilator in patients with LV failure or coronary spasm. Clinical trial results have suggested only a modest benefit from nitroglycerin therapy. A pooled analysis of more than 60,000 patients treated with nitrate-like preparations intravenously or orally in 22 trials revealed a mortality rate of 7.7% in the control group and 7.4% in the nitrate group. These data are consistent with a possible small treatment effect of nitrates on mortality rates (three to four fewer deaths for every 1000 patients treated).
Nitrates should be avoided in patients with initial systolic BP less than 90 mm Hg, marked bradycardia or tachycardia, and known or suspected RV infarction. Phosphodiesterase inhibitors potentiate the hypotensive effects of nitrates by releasing nitric oxide. Therefore, nitrates should not be administered to patients who have used a phosphodiesterase inhibitor for erectile dysfunction in the prior 24 to 48 hours.
Patients with ongoing ischemic discomfort should receive sublingual nitroglycerin (0.4 mg) every 5 minutes for a total of three doses, after which an assessment should be made about the need for IV administration. A useful IV regimen uses an initial infusion rate of 5 to 10 µg/min with increases of 5 to 20 µg/min until symptoms are relieved, or mean arterial BP is reduced by 10% of its baseline level in normotensive patients and up to 30% in hypertensive patients. In no case should the systolic pressure be brought below 90 mm Hg or drop 30 mm Hg below baseline. In view of their marginal treatment benefits, nitrates should not be used if hypotension limits the administration of β-blockers or angiotensin-converting enzyme (ACE) inhibitors, which have more powerful salutary effects.
The clinician should focus on two aspects of pain management: acute relief of the symptoms of ongoing myocardial ischemia and necrosis, and the general relief of anxiety and apprehension that frequently exacerbate pain. Pain, which may be severe in the acute phase of STEMI, contributes to the hyperadrenergic state that has been implicated as having a role in plaque fissuring and thrombus propagation, and in reducing the threshold for VF.
The tendency to underdose patients should be avoided. Control of cardiac pain typically is accomplished with a combination of nitrates, opiate analgesic agents, oxygen, and β-blockers. Morphine sulfate has remained the analgesic agent of choice for STEMI patients. The dose required varies in relation to age and body size as well as BP and heart rate. Morphine sulfate (2 to 4 mg intravenously with increments of 2 to 8 mg repeated at 5- to 15-minute intervals) may be given to a total dose of 10 to 30 mg as necessary. Morphine administration is particularly helpful in acute pulmonary edema, for which it may promote peripheral arterial and venous dilation. An important consideration when using IV nitrates is not to lower BP to a level that would preclude adequate dosing of morphine.
Side effects of morphine administration, such as hypotension, can be minimized by keeping the patient supine and elevating the lower extremities if systolic pressure drops below 100 mm Hg. The concomitant use of atropine in 0.5-mg doses intravenously may be helpful in reducing the excessive vagomimetic effects of morphine if significant bradycardia or hypotension occurs. Although respiratory depression is relatively uncommon, the respiration rate should be monitored, particularly as cardiovascular status improves. The narcotic-reversing agent naloxone, 0.4 to 2 mg intravenously every 3 minutes up to 10 mg, can reverse the effects of morphine if respiratory compromise occurs. Nausea and vomiting, which are potential side effects of large doses of morphine, may be treated with a phenothiazine. The use of nonsteroidal antiinflammatory drugs (NSAIDs), both nonselective as well as cyclooxygenase-2–selective agents, except for aspirin, should not be administered during hospitalization for STEMI because of the increased risk of death, reinfarction, hypertension, heart failure, and myocardial rupture.
In the Second International Study of Infarct Survival (ISIS-2), aspirin reduced 35-day mortality rate by 23%. When aspirin was combined with streptokinase, the relative reduction in mortality rate was 42%. A meta-analysis demonstrated that aspirin reduced coronary reocclusion and recurrent ischemic events after fibrinolytic therapy with either streptokinase or alteplase. The initial dose should be 162 to 325 mg (325 mg preferred for P-PCI). A maintenance dose of 81 mg daily should be continued indefinitely. This dose has been found to be as effective as higher doses and with less toxicity. Aspirin suppositories (300 mg) can be used safely for patients with severe nausea and vomiting or severe upper gastrointestinal problems. In patients with true aspirin hypersensitivity (e.g., hives, nasal polyps, bronchospasm, anaphylaxis), clopidogrel may be substituted with at least equal effectiveness if desensitization is not pursued. The use of ibuprofen or other NSAIDs may limit the cardioprotective effect of aspirin.
The Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT)/Second Chinese Cardiac Study (CCS-2) demonstrated a 13% reduction in death, MI, and stroke in medically managed patients treated within 12 hours of symptom onset with clopidogrel 75 mg daily. The Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-TIMI 28 trial demonstrated a 20% reduction in death, MI, and urgent revascularization in medically managed patients treated with a 300-mg loading dose of clopidogrel and a 75-mg daily maintenance dose as part of an early invasive strategy in patients younger than 75 years ( Figure 10-3 ). Neither trial showed an increase in major bleeding or intracranial hemorrhage (ICH). Therefore, for patients receiving fibrinolysis or no reperfusion therapy, dual antiplatelet therapy with aspirin and clopidogrel (with a loading dose of 300 mg in patients <75 years) is recommended. A loading dose of 600 mg is recommended for P-PCI. For patients on clopidogrel in whom CABG is planned, the drug should be withheld for at least 5 days (preferably 7 days) unless the urgent need for revascularization outweighs the risk of excess bleeding.
Prasugrel, a thienopyridine that achieves faster and greater platelet inhibition with less variability than clopidogrel, was superior to clopidogrel in STEMI patients in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel (TRITON)-TIMI 38 trial. All patients had planned PCI. The difference in the primary endpoint was due to fewer nonfatal MIs. In a post hoc analysis, patients with anterior MI seemed to benefit more from prasugrel. Patients 75 years or older, with body weight less than 60 kg or a history of stroke or transient ischemic attack, should not receive prasugrel. Prasugrel should be withheld if possible for 7 days before CABG or other major surgery. Prasugrel has not been studied in the setting of fibrinolysis.
Ticagrelor is a new non-thienopyridine-reversible P2Y 12 receptor antagonist that can be given orally and does not require hepatic metabolic conversion to an active form. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, a 180-mg oral loading dose of ticagrelor followed by 90 mg twice daily was superior to clopidogrel, including a decrease in mortality rate. Compared with clopidogrel, non-CABG bleeding rates were increased, but there was no significant difference in CABG related bleeding. Therefore, ticagrelor should be discontinued for at least 5 days before elective CABG.
Glycoprotein IIb/IIIa Inhibitors
Abciximab in combination with fibrinolytic therapy did not improve survival in two trials. It did reduce reinfarction rates in patients younger than 75 years with anterior STEMI, but it increased ICH rates in older patients. IV glycoprotein (GP) IIb/IIIa receptor inhibitors have also been studied as supportive antiplatelet therapy in patients undergoing PCI. However, much of the evidence was accumulated prior to the era of combined dual antiplatelet and anticoagulant therapy. A number of trials have evaluated GP IIb/IIIa antagonists as adjuncts to oral antiplatelet therapy in P-PCI for STEMI. These studies also looked at the timing of their administration. In light of the results of these and other trials, the current ACC/AHA guidelines have made the use of GP IIb/IIIa receptor antagonists (abciximab, high-dose tirofiban, and double-bolus eptifibatide) a class IIa recommendation if given at the time of P-PCI with or without stenting in selected patients with STEMI. It was suggested that the benefit would accrue more to patients with a large thrombus burden or patients who have not received adequate P2Y12 inhibitor loading. Studies comparing the intracoronary and IV delivery of the agents have been performed, and additional trials are ongoing.
Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are antithrombins. They decrease the rates of infarct artery reocclusion, deep venous thrombosis, pulmonary embolism, LV mural thrombus formation, and cerebral embolization. Anticoagulation is recommended in patients not receiving reperfusion therapy because data from the prethrombolytic era demonstrated benefit in the absence of other interventions.
Because streptokinase produces a systemic coagulopathy, additional antithrombin therapy with UFH offers the small advantage of only five lives saved per 1000 patients treated at a cost of one to two hemorrhagic strokes and three to five systemic bleeds ( Figure 10-4 ). Therapy is most useful in patients at high risk for systemic embolism, including patients with large or anterior MI, atrial fibrillation (AF), previous embolism, or known LV thrombus. With fibrin-specific agents (alteplase, reteplase, tenecteplase), UFH should be given intravenously with an aPTT target of 1.5 to 2.0 times control (50 to 70 seconds). A 60-U/kg bolus followed by a maintenance infusion of 12 U/kg/h (with a maximum of 4000 U bolus and 1000-U/h initial infusion) is recommended. During PCI for patients who did not receive prior UFH or fibrinolysis, a bolus dose of 70 to 100 U/kg with a target activated clotting time (ACT) of 250 to 300 seconds is recommended if no IV GP IIb/IIIa is used. If IV GP IIb/IIIa is used, the dose is reduced to a 50- to 70-U/kg bolus to achieve an ACT of 200 to 250 seconds. If the patients have received prior treatment with UFH, additional boluses should be given as needed during P-PCI to achieve the above goals. All patients should receive aspirin and an antiplatelet agent in addition to UFH. Prolonged treatment with UFH beyond 48 hours may result in heparin-induced thrombocytopenia (HIT).
LMWH can be considered an acceptable alternative to UFH as ancillary therapy for patients younger than 75 years who are receiving fibrinolytic therapy, provided significant renal dysfunction (serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) is not present. Enoxaparin (30 mg IV bolus followed 15 minutes later by 1.0 mg/kg subcutaneously [SC] every 12 hours until hospital discharge) used in combination with full-dose tenecteplase is the most comprehensively studied regimen in patients younger than 75 years ( Figure 10-5 ). However, older patients have an unacceptable excess rate of ICH with this dose. In those patients, the initial IV bolus is eliminated and the SC dose is reduced to 0.75 mg/kg every 12 hours. When combined with clopidogrel, LMWH is associated with significantly improved rates of infarct artery patency and lower rates of death/MI compared with UFH. Major bleeding occurred in 2.1% and 1.4% in the LMWH vs. UFH arms, respectively. Regardless of age, if the creatinine clearance is estimated to be less than 30 mL/min, the SC regimen is 1.0 mg/kg every 24 hours. For prior treatment with enoxaparin, if the last SC dose was administered at least 8 to 12 hours before planned PCI, an IV dose of 0.3 mg/kg should be given. If the last SC dose was administered within the prior 8 hours before PCI, no additional enoxaparin should be given. Maintenance dosing with enoxaparin should be continued for the duration of the hospitalization or until revascularization. The use of enoxaparin in the setting of P-PCI was recently shown to be superior to UFH in terms of reducing ischemic events, with comparable rates of bleeding. In a nonrandomized substudy of the Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial, enoxaparin seemed to be associated with a lower risk of adverse cardiovascular outcomes compared with UFH.
Direct Thrombin Inhibitors
Direct thrombin inhibitors such as bivalirudin bind to the substrate recognition and the catalytic sites of thrombin. In doing so, they directly block the formation of fibrin from fibrinogen and inhibit the thrombin-induced component of platelet aggregation. In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, major adverse cardiac event rates were identical in the bivalirudin monotherapy and UFH plus GP IIb/IIIa arms, but there was a decrease in major bleeding and all-cause mortality with bivalirudin (3.4% vs. 4.8%; P = .03). Concerns about the trial include its open label design, the administration of UFH before randomization in 66% of the patients in the bivalirudin arm, its definition of major bleeding, which included hematomas of 5 cm, and the composite primary endpoint of efficacy and safety. The occurrence of an increase in early stent thrombosis in the bivalirudin arm and the excess bleeding with UFH and GP IIb/IIIa inhibitors may have been related to the degree of platelet inhibition and the antithrombin activity associated with these treatments. Bivalirudin is an acceptable alternative to UFH and GP IIb/IIIa receptor blockers to support P-PCI with or without prior treatment with UFH, especially when there is an increased risk of bleeding complications.
Bivalirudin is useful in patients with HIT and/or at a high risk of bleeding. For patients who have received UFH, wait 30 minutes, then give a 0.75-mg/kg bolus, then 1.75 mg/kg/h infusion (reduce dose to 1 mg/kg/h in patients with creatine clearance of <30 mL/min) with aspirin and 600 mg clopidogrel. If no heparin was given, proceed immediately with the bolus and infusion.
Fondaparinux, a pentasaccharide indirect factor Xa inhibitor that is rarely used in the United States, was evaluated in the Sixth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 6) trial. The benefits of fondaparinux were confined to those receiving fibrinolytic therapy or not undergoing reperfusion therapy, for which there was less bleeding. No benefit and a trend toward harm were seen in patients undergoing P-PCI. The dose is 2.5 mg initially IV with subsequent SC injections of 2.5 mg once daily for the duration of the hospitalization (with serum creatinine <3.0 mg/dL).
β-Blockers diminish myocardial oxygen demand by reducing heart rate, systemic arterial pressure, and myocardial contractility. Reduction in heart rate prolongs the diastolic period and may augment perfusion to the subendocardium. In patients not receiving fibrinolytic therapy, early trials suggested reduction in infarct size and mortality rate. In patients receiving fibrinolytic therapy, recent trials have not found a mortality rate reduction, although recurrent ischemia and reinfarction rates were reduced. It has also been suggested that β-blockers decrease ventricular arrhythmias and decrease the risk of intracerebral hemorrhage with lytic therapy. The evidence base for β-blocker therapy was developed more than 25 years ago in a treatment environment that differs from contemporary practice. COMMIT/CCS-2 underscored the potential risk of administering IV β-blockers to patients with severe heart failure or cardiogenic shock. The use of IV β-blockers is reasonable in patients who are hypertensive at the time of presentation and who do not have signs of heart failure, evidence of a low output state, or risk for the development of cardiogenic shock (age >70 years, systolic BP <120 mm Hg, sinus tachycardia >110 beats/min, heart rate <60 beats/min) or other relative contraindications, such as marked first-degree atrioventricular (AV) block, second- or third-degree AV block, or active asthma or reactive airway disease. Otherwise, oral β-blockers should be initiated in the first 24 hours, unless there are contraindications, and titrated as tolerated for the duration of the index hospitalization. Patients who cannot tolerate β-blockade in the first 24 hours (those with moderate or severe LV failure) should be reevaluated for therapy as secondary prevention. It is prudent to begin with metoprolol 25 to 50 mg (or its equivalent) every 6 hours, transitioning to a maximal dose of 200 mg/day orally, or the maximum tolerated dose. If bradycardia or hypotension occurs with therapy, isoproterenol 1 to 5 µg/min can be administered.
All STEMI patients should undergo rapid evaluation for reperfusion therapy and have a reperfusion strategy promptly implemented after contact with the medical system. Although rapid spontaneous reperfusion of the occluded infarct artery may occur, restoration of flow usually requires either fibrinolytic therapy or P-PCI. A system plan for triage and transfer should be in place (see Figure 10-2 ). Early, complete, and sustained infarct artery patency is a key determinant of both short- and long-term prognosis regardless of whether reperfusion is accomplished by fibrinolysis or P-PCI. Reperfusion therapy should be administered to patients with STEMI with symptom onset within the previous 12 hours and perhaps within 12 to 24 hours with clinical evidence of ongoing ischemia. P-PCI is the preferred method of reperfusion when it can be performed in a timely fashion by experienced operators. Every effort should be made to shorten the time from symptom onset to contact with the medical system and to implement a reperfusion strategy with the concept of medical system goals. These include a first medical contact-to-needle (or EMS-to-needle) time for fibrinolytic therapy within 30 minutes or a first medical contact-to-balloon (or EMS-to-balloon) time for P-PCI within 90 minutes in at least 75% of nontransferred patients with STEMI. These goals should not be understood as “ideal” times, but rather the longest times that should be considered acceptable in every appropriate patient unless there is a good reason for delay, such as uncertainty about the diagnosis, need for the evaluation and treatment of other life-threatening conditions (e.g., respiratory failure), or delays associated with the patient’s informed choice to consider therapy. Transfer from a non–PCI-capable hospital to a PCI-capable hospital for angiography and P-PCI is preferred if it can be accomplished consistently with a first medical contact to balloon or device time of less than 120 minutes. Fibrinolytic therapy should be administered in the absence of contraindications if the anticipated first medical contact-to-device time exceeds 120 minutes. For those presenting to a non–PCI-capable hospital, rapid assessment of 1) the time from onset of symptoms, 2) the mortality risk of STEMI based on patient characteristics and infarct location, 3) the risk of bleeding, and 4) the time required for transfer and the interval from first medical contact to balloon or device must all be considered.
Even when fibrinolysis or P-PCI is successful in restoring infarct artery flow, perfusion of the infarct zone may still be compromised by a combination of microvascular damage and reperfusion injury.
Time from Symptom Onset
Fibrinolytic therapy administered within the first 2 (especially the first) hours can occasionally abort MI and dramatically reduces mortality rates. Prehospital fibrinolysis reduces treatment delays by up to 1 hour, allowing the majority of patients to be treated within 2 hours of symptom onset, and reduces mortality rates by 17% compared with therapy initiated in the hospital. However, the efficacy of fibrinolytic agents in lysing thrombus diminishes with increasing treatment delays. In contrast, P-PCI can seldom be performed within 2 hours of symptom onset, but reperfusion rates are superior to fibrinolytic therapy and independent of time. Although the Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction (CAPTIM) and Primary Angioplasty in Patients Transferred from General Community Hospitals to Specialized PTCA [percutaneous transluminal coronary angioplasty] Units with or Without Emergency Thrombolysis (PRAGUE)-2 studies reached different conclusions about the overall superiority of P-PCI over fibrinolysis, similar results were seen in time-to-treatment subset analyses. Patients treated within 2 hours of symptom onset in CAPTIM had improved outcomes with prehospital tissue plasminogen activator versus transfer for P-PCI. Patients treated within 3 hours of symptom onset in PRAGUE-2 had equivalent mortality rate whether treated with streptokinase or transferred for P-PCI. Conversely, both studies showed superior outcomes with P-PCI in patients with symptom duration greater than 3 hours.
Risk Stratification in ST-Segment Elevation Myocardial Infarction
Different risk stratification tools are available to quantify risk ( Figure 10-6 ). Patients with low mortality risk have similar outcomes with fibrinolysis or P-PCI. Patients with anterior STEMI, older age, congestive heart failure, or cardiogenic shock have better outcomes with P-PCI. The point of equipoise between strategies is an estimated 30-day mortality risk of 3%.
Risk of Bleeding
The higher the risk of bleeding with fibrinolytic therapy, the more P-PCI would be favored as the reperfusion strategy. The increased risk for ICH in the elderly is a strong factor that favors P-PCI in this subgroup.
Predicted Transfer and Door-to-Balloon Time
P-PCI is superior to fibrinolytic therapy when it can be performed expeditiously by experienced teams in high-volume hospitals. The benefit noted in the randomized, clinical trials ( Figure 10-7 ) was strongly influenced by a reduction of nonfatal recurrent MI. Several trials have suggested a benefit from transferring patients from a non–PCI-capable hospital to a PCI-capable hospital for P-PCI. In the United States, only 25% of hospitals are capable of performing P-PCI. Although several trials have suggested a benefit to transferring patients, transfer times remain unreasonably long. In the National Cardiovascular Data Registry, only 9.9% of transferred patients were treated with P-PCI within 90 minutes, and approximately 30% had door-to-balloon times greater than 3 hours. When the anticipated time from first medical contact to device exceeds 120 minutes, fibrinolysis should be administered in the absence of contraindications.
Indications and Contraindications
In the absence of contraindications, and when there is a delay to P-PCI, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours and ST-segment elevation greater than 0.1 mV in at least two contiguous leads, or new, or presumably new, LBBB. Patients with true posterior MI and patients with symptom duration for 12 to 24 hours and ST-segment elevation are also reasonable candidates. Contraindications and cautions for using fibrinolytic therapy are shown in Box 10-1 . Hemorrhage is the most critical risk, especially ICH, which is fatal in more than half of patients. Several models for estimating the risk of ICH after fibrinolysis have been developed. Patients with more than 4% risk of ICH should be treated with P-PCI rather than fibrinolytic therapy. Streptokinase without heparin has the lowest ICH rate.
Any prior ICH
Known structural cerebral vascular lesion (e.g., atrioventricular malformation)
Known malignant intracranial neoplasm (primary or metastatic)
Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed head or facial trauma within 3 months
History of chronic, severe, poorly controlled hypertension
Severe uncontrolled hypertension on presentation (SBP > 180 or DBP > 110 mm Hg) †
† Could be an absolute contraindication in low-risk patients with myocardial infarction.
History of prior ischemic stroke >3 months, dementia, or known intracranial pathology not covered in contraindications
Traumatic or prolonged (>10 minutes) CPR or major surgery (<3 weeks)
Recent (within 2-4 weeks) internal bleeding
Noncompressible vascular punctures
For streptokinase/anistreplase: prior exposure or prior allergic reaction to these agents
Active peptic ulcer
Current use of anticoagulants: the higher the INR, the higher the risk of bleeding
CPR, cardiopulmonary resuscitation; DBP, diastolic blood pressure; ICH, intracranial hemorrhage; INR, international normalized ratio; SBP, systolic blood pressure; STEMI, ST-segment elevation myocardial infarction.
Placebo-controlled trials have demonstrated the survival benefit associated with fibrinolytic therapy. Mortality reduction is greatest within the first few hours of symptoms, especially the first hour, because of salvage of ischemic myocardium with reduced infarct size. The mortality benefit seen with later treatment depends more on improved infarct healing and myocardial remodeling, reduced electrical heterogeneity, and potential for life-threatening ventricular arrhythmias. Patients with LBBB, anterior MI, hypotension, and tachycardia have higher risk from STEMI and achieve greater therapeutic benefit. The patient risk and potential therapeutic benefit in inferior MI is increased with RV involvement, precordial ST-segment depression, or complete heart block. The number of ECG leads involved and the extent of ST-segment deviation is an excellent predictor of potential STEMI risk. Although patients older than 75 years might better be treated with PCI, the absolute number of lives saved per 1000 patients treated with fibrinolytic therapy compared with placebo is actually greater than in younger patients (34 vs. 28).
Effect on Left Ventricular Function
Successful early reperfusion reduces infarct size, preserves regional wall motion, decreases ventricular dilation, and maintains global LV function, an important predictor of survival. Restoration of normal infarct artery flow does not reflect microvascular reperfusion, which is better evaluated by myocardial blush on angiography, contrast perfusion on echocardiography, or prompt resolution of ST-segment elevation on ECG. Poor microvascular reperfusion is associated with increased infarct size, morbidity, and death.
The major complication of fibrinolytic therapy is hemorrhage, which may or may not require transfusion. Risk factors include older age, female gender, lower body weight, and hypertension. ICH encompasses parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural hematoma, and epidural hematoma. Typical presenting features include an acute change in level of consciousness, unifocal or multifocal neurologic signs, coma, headache, nausea, vomiting, and seizures. The occurrence of a change in neurologic status during or after reperfusion therapy, particularly within the first 24 hours after initiation of treatment, is considered to be caused by ICH until proven otherwise ( Figure 10-8 ). Fibrinolytic, antiplatelet, and anticoagulant therapies should be discontinued until a brain imaging scan shows no evidence of ICH. Neurology and/or neurosurgery consults should be obtained as dictated by clinical circumstances. Immediate measures to reduce intracranial pressure include mannitol infusion, elevation of the head of the bed to 30 degrees, endotracheal intubation, and hyperventilation to achieve a pCO 2 of 25 to 30 mm Hg. Cryoprecipitate (10 U) will increase the fibrinogen level by approximately 0.70 g/L and the factor VIII level by approximately 30% in a 70-kg adult. Fresh frozen plasma restores levels of factors V and VIII. Protamine (1 mg/100 U of UFH given in the preceding 4 hours) reverses heparin anticoagulation. Platelet transfusions (6 to 8 U) can be given if the bleeding time is abnormal. BP and blood glucose levels should be optimized. Neurosurgical evacuation of ICH may be required in selected patients.
Comparison of Fibrinolytic Agents
Fibrinolytic agents are plasminogen activators. Plasmin dissolves the fibrin mesh that holds red blood cells and platelets together as a thrombus. The four approved IV agents are compared in Table 10-2 . Alteplase is superior to streptokinase in reducing morbidity and mortality but is more expensive and confers a slightly higher risk of ICH. Bolus dosing with reteplase or tenecteplase produces equivalent results compared with alteplase. The cost/benefit ratio is more favorable for the expensive agents in patients with a large myocardial area of risk and a low risk of ICH. Streptokinase is used by some clinicians when predicted infarct size is small or ICH risk is higher, but should not be reused because of the high prevalence of neutralizing antibody titers.
|Dose||1.5 MU over 30-60 min||Up to 100 mg in 90 min (based on weight) *||10 U × 2, each over 2 min||30-50 mg (based on weight) †|
|Allergic reactions (hypotension most common)||Yes||No||No||No|
|Systemic fibrinogen depletion||Marked||Mild||Moderate||Minimal|
|90-min patency rates (approximate %)||50||75||75||75|
|TIMI grade 3 flow (%)||32||54||60||63|
|Cost (in dollars) per dose||$613||$2974||$2750||$2833 for 50 mg|
Percutaneous Coronary Intervention
More than 90% of STEMI patients are candidates for P-PCI. Patency rates greater than 90% and TIMI-3 flow rates of 70% to 90% have been reported. If immediately available, P-PCI should be performed in patients with STEMI (including true posterior MI) or MI with new, or presumably new, LBBB who can undergo PCI of the infarct artery within 12 hours of symptom onset (or >12 hours if ischemic symptoms persist), if performed in a timely fashion (balloon inflation within 90 minutes of presentation) by persons skilled in the procedure (individuals who perform more than 75 PCI procedures per year). The procedure should be supported by experienced personnel in an appropriate laboratory environment (that performs more than 400 PCI procedures per year, of which at least 36 are P-PCI for STEMI, and has cardiac surgery capability).
Randomized clinical trials performed in selected patients by experienced providers demonstrated that PCI-treated patients experience lower short-term mortality rates (5.0% vs. 7.0%; relative risk [RR], 0.70; 95% confidence interval [CI], 0.58 to 0.85; P = .0002), less nonfatal reinfarction (3.0% vs. 7.0%; RR, 0.35; 95% CI, 0.27 to 0.45; P = .0003), and less hemorrhagic stroke (0.05% vs. 1.0%; RR, 0.05; 95% CI, 0.006 to 0.35; P = .0001) than those treated by fibrinolysis, but with an increased risk for major bleeding (7.0% vs. 5.0%; RR, 1.3; CI, 1.02 to 1.65; P = .032) (see Figure 10-7 ). The efficacy differences are smaller when PCI is compared with alteplase, the invasive strategy is allowed after fibrinolytic therapy, patients are treated by less-experienced operators or in low-volume facilities, or door-to-balloon times are excessively prolonged.
The survival benefit with P-PCI is time dependent ( Figure 10-9 ). To reproduce the outcomes in the randomized trials in which P-PCI was performed by experienced operators with an additional mean treatment delay of 40 minutes for P-PCI instead of fibrinolytic therapy, strict performance criteria must be followed. These include door-to-balloon times less than 90 minutes, TIMI 2/3 flow rates in more than 90% of patients, emergency bypass surgery rates less than 2%, and performance of P-PCI in more than 85% of patients brought to the laboratory. Risk-adjusted hospital mortality rates should be less than 7% in patients without cardiogenic shock, which would be comparable to that reported for fibrinolytic therapy and consistent with previously reported registry results for which mortality rates were not different between treatment strategies. If the performance criteria stated above cannot be met, fibrinolytic therapy should be considered unless it is contraindicated.
P-PCI has its greatest mortality benefit in high-risk patients. P-PCI has been associated with an absolute 9% reduction in 30-day mortality rate in cardiogenic shock and a 33% relative risk reduction (vs. 9% with fibrinolytic therapy) in congestive heart failure. Compared with fibrinolytic therapy, P-PCI reduces mortality rates in patients with anterior MI, but there is no difference in patients with nonanterior MI. Reocclusion rates are 15% after percutaneous transluminal coronary angioplasty (PTCA) and 5% after stenting compared with 30% after fibrinolytic therapy. Potential complications include problems with the arterial access site; adverse reactions to volume loading, contrast medium, and antithrombotic medications; technical complications; and reperfusion events.
Recommended adjunctive antiplatelet and antithrombotic therapy to support perfusion with P-PCI is presented in Tables 10-3 and 10-4 .
|ANTIPLATELET THERAPY||CLASS||LEVEL OF EVIDENCE|
|Preprocedure: 325 mg||I||A|
|Postprocedure: 81-160 mg/day indefinitely||I||A|
|Maintenance: 81 mg/day||IIa||B|
|Clopidogrel: 600 mg as early as possible before or at the time of PCI||I||B|
|Prasugrel: 60 mg at PCI||I||B|
|Ticagrelor: 180 mg at PCI||I||B|
|Maintenance Dose with DES ≤1 Year|
|Clopidogrel: 75 mg/day||I||C|
|Prasugrel: 10 mg/day||I||B|
|Ticagrelor: 90 mg bid †||I||B|
|Duration of Therapy ≥1 year||IIb||C|
|Maintenance Dose with BMS or Balloon Angioplasty Only *|
|Clopidogrel: 75 mg/day||I||B|
|Prasugrel: 10 mg/day||I||B|
|Prasugrel in STEMI patients with prior stroke/TIA, weight <60 kg, or age ≥75 years or greater||III||B|
|Ticagrelor: 90 mg bid||I||B|
|GP IIb/IIIa Receptor Antagonists (in Conjunction with UFH) in Patients with Large Thrombus Burden|
|Abciximab: 0.25 mg/kg IV bolus, then 0.125 µg/kg/min (maximum 10 µg/min) up to 12 hours||IIa||A|
|Abciximab: 0.25 mg IC bolus||IIb||B|
|Eptifibatide (double bolus): 180 µg/kg IV bolus, then 2 µg/kg/min; a second 180 µg/kg bolus is administered 10 min after the first bolus||IIa||B|
|In patients with CrCl <50 mL/min (Cockcroft-Gault formula), give single bolus and reduce infusion by 50%||IIa||B|
|Tirofiban (high bolus dose): 25 µg/kg IV bolus, then 0.15 µg/kg/min||IIa||B|
|In patients with CrCl <50 mL/min (Cockcroft-Gault formula), reduce infusion by 50%||IIa||B|
|GP IIb/IIIa inhibitors in conjunction with bivalirudin||IIb||B|
|ANTICOAGULANT THERAPY||CLASS||LEVEL OF EVIDENCE|
|UFH to maintain ACT|
|With GP IIb/IIIa receptor antagonist planned: 50-70 U/kg bolus IV to achieve ACT of 200-250 sec||I||C|
|No GP IIb/IIIa receptor antagonist planned: 70-100 U/kg bolus to achieve ACT of 250-300 sec for HemoTec, 300-350 sec for Hemochron||I||C|
|0.75 mg/kg IV bolus, then 1.75 mg/kg/h infusion, with or without prior treatment with UFH, to achieve therapeutic ACT for the duration of the procedure; an additional bolus of 0.3 mg/kg may be given if needed||I||B|
|Reduce infusion to 1 mg/kg/h with estimated CrCl <30 mL/min||IIa||B|
|Preferred over UFH with GP IIb/IIIa receptor antagonists or LMWH with GP IIb/IIIa receptor antagonists in patients at high risk of bleeding||IIa||B|
|Fondaparinux: not recommended as sole anticoagulant for primary PCI||III||B|
Use of Stents
Compared with PTCA, intracoronary stents achieve a better immediate angiographic result with a larger arterial lumen, less reocclusion and restenosis of the infarct artery, and fewer subsequent ischemic events, but there are no differences in mortality or reinfarction rates. Studies comparing bare-metal stents (BMS) with drug-eluting stents (DES) in STEMI show no differences in mortality rate, MI rate, or stent thrombosis risk. The major advantage of DES over BMS in this setting is a small reduction in target vessel revascularization rates. The greatest challenge in selecting patients for DES implantation during STEMI, however, is determining in an emergency situation whether the patient is a candidate for prolonged dual antiplatelet therapy. Financial barriers and social barriers that may limit patient compliance, or medical issues that involve bleeding risks or the need for invasive or surgical procedures in the following year that would interrupt antiplatelet therapy, must be considered.
Two small trials and a meta-analysis support the use of aspiration thrombectomy for STEMI. The concept is to minimize atherothrombotic debris, limit microvascular obstruction, and maximize myocardial salvage. It is reasonable to perform aspiration thrombectomy in patients undergoing P-PCI and in patients with short ischemic times and large thrombus burdens.
P-PCI is the preferred choice of treatment for STEMI if it can be performed in a timely manner by experienced operators. Unfortunately, only 25% of hospitals in the United States are capable of performing P-PCI, and transfer times from non–PCI-capable to PCI-capable hospitals are often unreasonably long. IV fibrinolytic therapy fails to restore infarct artery patency in 25% to 50% of patients. The REACT trial showed a benefit of PCI performed in patients with moderate to high risk with failed reperfusion following fibrinolytic therapy versus repeat fibrinolysis. Several strategies have been developed to test whether a pharmaco-invasive strategy could accomplish the goal of timely reperfusion, especially for patients presenting at a non–PCI-capable hospital. Different combinations of antithrombotic regimens (full- or half-dose fibrinolytic agents, antithrombins, GP IIb/IIIa receptor blockers, dual antiplatelet therapy) prior to P-PCI have been compared with standard P-PCI without significant clinical benefit. Six trials and a meta-analysis have shown promise for the early transfer strategy: fibrinolytic therapy at a non–PCI-capable hospital followed by transfer to a PCI-capable hospital for routine angiography and probable PCI within 24 hours following STEMI for high-risk patients. This is in contrast to the “ischemia-driven” approach, in which only those who show signs of hemodynamic instability or failed reperfusion are sent for angiography.
Patients best suited for transfer for PCI are STEMI patients who present with high-risk features, those with a high risk of bleeding, and patients presenting late (more than 4 hours after onset of symptoms). Patients best suited for fibrinolytic therapy present early after symptom onset with low bleeding risk. After fibrinolytic therapy, if the patient is not at high risk, transfer to a PCI-capable facility may be considered, especially if symptoms persist and failure to reperfuse is suspected.
The Occluded Artery Trial (OAT) demonstrated that routine PCI for total occlusions 1 to 28 days after STEMI in stable patients did not reduce the composite of death, reinfarction, or class IV heart failure provided the patients received optimal medical therapy. Patients who were in New York Heart Association (NYHA) class III or IV, had rest angina or inducible ischemia, had a creatinine level greater than 2.5 mg/dL, were clinically unstable, or had main left or triple-vessel disease were excluded.
Hospitals Without on-Site Cardiac Surgery
Whereas hospitals with onsite cardiac surgery can offer immediate access to a PCI laboratory, hospitals without this resource must establish more complicated treatment protocols that include interhospital transfer agreements. Fibrinolytic therapy will usually be the primary reperfusion strategy. However, many patients are ineligible for fibrinolytic therapy because of bleeding risk and should be considered for transfer for P-PCI. Patients who do not respond to fibrinolysis and are candidates for rescue PCI should also be transferred, as should patients with congestive heart failure or cardiogenic shock.
Some hospitals with cardiac catheterization laboratories are able to offer P-PCI without on-site cardiac surgery. Several performance criteria must be met for this strategy to reproduce the favorable results in published reports ( Box 10-2 ). The operators must be experienced interventionalists (performing at least 75 interventions per year), the lab must perform at least 36 procedures per year, and the nursing and technical staff must be fully trained. The full range of PCI equipment must be available, and intraaortic balloon counterpulsation expertise is required. Appropriate case selection and continuous quality improvement are important components ( Box 10-3 ). High-risk patients should be transferred to a hospital with on-site surgery for P-PCI.
The operators must be experienced interventionalists who regularly perform elective PCI at a surgical center (at least 75 cases/year). The catheterization laboratory must perform a minimum of 36 primary PCI procedures per year.
The nursing and technical catheterization laboratory staff must be experienced in handling acutely ill patients and be comfortable with interventional equipment. They must have acquired experience in dedicated interventional laboratories at a surgical center and participate in a 24-hour, 365-day call schedule.
The catheterization laboratory itself must be well equipped, with optimal imaging systems, resuscitative equipment, IABP support, and a broad array of interventional equipment.
The cardiac care unit nurses must be adept in hemodynamic monitoring and IABP management.
The hospital administration must fully support the program and enable the fulfillment of the above institutional requirements.
Formalized written protocols must be in place for immediate and efficient transfer of patients to the nearest cardiac surgical facility that are reviewed/tested on a regular (quarterly) basis.
Primary PCI must be performed routinely as the treatment of choice for a large proportion of patients with STEMI to ensure streamlined care paths with increased case volumes.
Case selection for the performance of primary PCI must be rigorous. Criteria for the types of lesions appropriate for primary PCI and for the selection for transfer for emergent aortocoronary bypass surgery are shown in Table 11-5 .
An ongoing program of outcomes analysis and formalized periodic case review must be in place.
Institutions should participate in a 3- to 6-month period of implementation during which time development of a formalized primary PCI program is instituted that includes establishing standards, training staff, detailed logistic development, and creation of a quality assessment and error management system.
IABP, intraaortic balloon pump; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
Avoid Intervention in Hemodynamically Stable Patients with
Significant (≥60%) stenosis of an unprotected left main coronary artery upstream from an acute occlusion in the left coronary system that might be disrupted by the angioplasty catheter
Extremely long or angulated infarct-related lesions with TIMI grade 3 flow
Infarct-related lesions with TIMI grade 3 flow in stable patients with triple-vessel disease
Infarct-related lesions of small or secondary vessels
Hemodynamically significant lesions in other than the infarct artery
Transfer Patients for Emergency Aortocoronary Bypass Surgery
After primary PCI of occluded vessels if high-grade residual left main or multivessel coronary disease with clinical or hemodynamic instability is present (preferably with intraaortic balloon pump support)
PCI, percutaneous coronary intervention; TIMI, Thrombolysis In Myocardial Infarction.
Patients should be admitted to the coronary care unit (CCU) or monitored step-down unit with immediate access to defibrillators. Initial patient evaluation includes assessment of vital signs, pulse oximetry, cardiac rhythm and ST segments, and symptoms of acute cardiac ischemia. Outstanding (and abnormal) results should be followed up, and standard admitting orders should be implemented ( Box 10-4 ). Intraarterial and pulmonary artery pressure monitoring should be available for hypotensive patients. Intra-aortic balloon pumps (IABPs) or other ventricular assist devices should be available for treatment of cardiogenic shock. Oral β-blocker therapy should be administered in an adequate dose to control heart rate. IV nitroglycerin is useful for control of angina, hypertension, or acute heart failure. Oxygen can be discontinued if the oxygen saturation is greater than 90%.
IV: Normal saline or 5% dextrose in water to keep vein open. Start a second IV if IV medication is being given. This may be a heparin lock.
Vital signs: Every 30 minutes until stable, then every 4 hours as needed. Notify physician if heart rate is <60 beats/min or >100 beats/min, SBP is <100 mm Hg or >150 mm Hg, respiratory rate is <8 breaths/min or >22 breaths/min.
Monitor: Continuous ECG monitoring for arrhythmia and ST-segment deviation.
Diet: NPO except for sips of water until stable. Then start sodium 2 g/day, low saturated fat (<7% of total calories/day) and low-cholesterol (<200 mg/day) diet, such as Therapeutic Lifestyle Changes diet.
Activity: Bed rest and bedside commode and light activity when stable.
Oxygen: Continuous oximetry monitoring. Nasal cannula at 2 L/min. When stable for 6 hours, discontinue oxygen and assess for oxygen need (i.e., <90% saturation), and consider discontinuing oxygen.
Use sublingual NTG 0.4 mg q5min as needed for chest discomfort
IV NTG for CHF, hypertension, or persistent ischemia
If ASA not given in the ED, chew non-enteric-coated ASA 162-325 mg. †
† Although some trials have used enteric-coated aspirin for initial dosing, more rapid buccal absorption occurs with non-enteric-coated formulations.
If ASA has been given, start daily maintenance of 75-162 mg. May use enteric-coated ASA for gastrointestinal protection.
If not given in the ED, assess for contraindications (i.e., bradycardia and hypotension). Continue daily assessment to ascertain eligibility for β-blocker.
If given in the ED, continue daily dose and optimize as dictated by HR and BP.
Start ACE inhibitor orally in patients with anterior infarction, pulmonary congestion, or LVEF <40% if the following are absent: hypotension (SBP <100 mm Hg or <30 mm Hg below baseline) or known contraindications to this class of medications.
Start ARB orally in patients who are intolerant of ACE inhibitors and who have either clinical or radiologic signs of heart failure or LVEF <40%.
IV morphine sulfate 2-4 mg with increments of 2-8 mg at 5- to 15-minute intervals as needed to control pain.
Anxiolytics (based on a nursing assessment)
Daily stool softener
Serum biomarkers for cardiac damage, *
* Do not wait for results before implementing reperfusion strategy.CBC with platelet count, INR, aPTT, electrolytes, magnesium, BUN, creatinine, glucose, serum lipids
ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; aPTT, activated partial thromboplastin time; ASA, aspirin; BP, blood pressure; BUN, blood urea nitrogen; CBC, complete blood count; CHF, congestive heart failure; ECG, electrocardiogram; ED, emergency department; HR, heart rate; INR, international normalized ratio; IV, intravenous; LVEF, left ventricular ejection fraction; NPO, nothing by mouth; NTG, nitroglycerin; SBP, systolic blood pressure; STEMI, ST-segment elevation myocardial infarction.
Nursing care should be provided by individuals certified in critical care, with staffing based on the specific needs of patients and provider competencies as well as organizational priorities. Patients should be monitored for the development of heart failure, serious arrhythmias, or recurrent ischemia. Medications such as stool softeners and antianxiety agents should be given based on nursing judgment.
Patients typically are transferred to a monitored bed in a step-down unit after 12 to 24 hours of clinical stability. Similarly, low-risk patients who have undergone successful PCI can be directly admitted to the step-down unit for post-PCI care rather than to the CCU. Pulse oximetry, ECG monitoring, and defibrillation equipment should be available. The nursing staff should have a skill set similar to CCU nurses so they may evaluate and respond to any clinical complications.
Bed rest should be limited to 12 to 24 hours because of the concern about physical deconditioning and orthostatic hypotension. Patients should have no oral intake before a procedure, but otherwise should be prescribed the National Cholesterol Education Program’s Adult Treatment Panel III Therapeutic Lifestyle Changes diet focusing on reduced intake of fats and cholesterol, less than 7% of total calories as saturated fats, less than 200 mg/day of cholesterol, increased consumption of omega-3 fatty acids, and appropriate caloric intake for energy needs. Diabetic patients need an appropriate diet, and sodium intake should be restricted in patients with hypertension or heart failure. Patient counseling regarding risk factor modification, including smoking cessation, medication compliance, diet, and exercise should be part of every patient encounter.
It is reasonable to use anxiolytic medications to alleviate short-term anxiety. Withdrawal of caffeine is associated with headache and increases in heart rate. One to two cups of coffee a day, enough to avert caffeine withdrawal, has not been associated with BP increases or ventricular arrhythmias. Smokers may experience symptoms of nicotine withdrawal, including anxiety, insomnia, depression, difficulty concentrating, irritability, anger, restlessness, and slowed heart rate. Anxiolytics, bupropion, and nicotine replacement therapy are treatment options. IV haloperidol is a rapidly acting neuroleptic that can be given to cardiac patients with agitation. Communication with the patient and family, liberalized visiting rules, psychological support, and counseling can decrease anxiety and depression for both the patient and the family members.
IV nitroglycerin is indicated in the first 48 hours after STEMI for treatment of persistent ischemia that responds to nitrate therapy, CHF, or hypertension. Intravenous, oral, or topical nitrates are useful beyond the first 48 hours after STEMI for treatment of recurrent angina or persistent CHF if their use does not preclude therapy with β-blockers or ACE inhibitors. The continued use of nitrate therapy beyond the first 24 to 48 hours in the absence of symptoms is not well established in current practice. If sustained nitrate therapy is planned, a nitrate-free interval during daily dosing is important to avoid nitrate tolerance.
Aspirin should be continued indefinitely unless aspirin allergy exists. Low-dose aspirin (81 mg/day) is preferred for long-term treatment because of a dose-dependent increase in bleeding risk. A thienopyridine should be substituted for aspirin when aspirin is contraindicated because of hypersensitivity or major gastrointestinal intolerance. Gastric side effects may be reduced by administration of proton pump inhibitors, H2 antagonists, antacids, or use of enteric-coated aspirin. Available data suggest that dual antiplatelet therapy with both aspirin and either clopidogrel, prasugrel, or ticagrelor should be continued for at least 1 year in all patients.
IV UFH should be used for up to 48 hours in patients not undergoing P-PCI. Similarly, enoxaparin and fondaparinux should be continued for the duration of the hospitalization up to 8 days or until revascularization. Anticoagulants are discontinued in patients at the conclusion of P-PCI so that the vascular sheaths can be removed. Deep venous thrombosis prophylaxis with SC LMWH (dosed appropriately for specific agent) or with SC UFH (7500 to 12,500 U twice daily) until the patient is completely ambulatory may be useful, but the effectiveness of such a strategy is not well established in the contemporary era of routine aspirin use and early mobilization.
An aPTT measurement and dose adjustment should be made 3 hours after starting IV UFH therapy and repeated 6 hours after each dose adjustment and daily thereafter. Rather than abruptly stopping therapy, reducing UFH infusions in a gradual fashion (e.g., by half within 6 hours, then discontinuing over the subsequent 12 hours) may decrease the risk of hypercoagulability from heparin rebound. Platelet counts should be monitored daily because of the 3% risk of HIT.
Meta-analysis of trials from the pre-fibrinolytic era involving more than 24,000 patients who received β – blockers in the convalescent phase has shown a reduction in acute ischemic events and a 23% reduction in long-term mortality rate. The risk is a 3% incidence of provocation of congestive heart failure or complete heart block and a 2% incidence of cardiogenic shock. β – Blockers are especially beneficial in patients with persistent or recurrent ischemia, evidence for infarct extension, or tachyarrhythmias. Initiation of therapy can be undertaken within 24 to 48 hours of freedom from relative contraindications that include bradycardia and congestive heart failure. Commonly used β – blockers are metoprolol tartrate 25 to 50 mg every 6 to 12 hours orally, then transitioning to twice-daily dosing for metoprolol tartrate or daily dosing of metoprolol succinate titrated to a dose of 200 mg as tolerated, or carvedilol beginning with 3.125 to 6.25 mg twice daily, titrated to 25 mg twice daily as tolerated.
Inhibition of the Renin-Angiotensin-Aldosterone System
An ACE inhibitor should be administered orally during convalescence in patients who tolerate this class of medication. ACE inhibitors should not be used if systolic BP is less than 100 mm Hg or less than 30 mm Hg below baseline in the presence of clinically relevant renal failure, a history of bilateral renal artery stenosis, or known allergy to ACE inhibitors. The proportional benefit of ACE inhibitor therapy is largest in higher risk subgroups: patients with previous MI, heart failure, depressed LV ejection fraction (LVEF), or tachycardia. These patients should receive long-term therapy. Survival benefit for the elderly and low-risk subgroups is less robust. Treatment can be initiated with captopril or an equivalent, 6.25 to 12.5 mg three times daily, and titrated to 50 mg three times daily. If tolerated, a once- or twice-daily ACE inhibitor (lisinopril 2.5 to 5 mg daily titrated to 10 mg daily as tolerated, or ramipril 2.5 mg twice daily titrated to 5 mg twice daily as tolerated) can be substituted.
An angiotensin receptor blocker should be administered to STEMI patients who are intolerant of ACE inhibitors and with either clinical or radiologic signs of heart failure or LVEF of 40% or less. Valsartan (beginning with 20 mg twice daily for a target dose 80 mg twice daily) and candesartan (beginning with 4 mg daily for a target dose 32 mg daily) have demonstrated efficacy for this recommendation.
Long-term aldosterone blockade should be prescribed for patients without significant renal dysfunction (creatinine ≤2.5 mg/dL in men and ≤2.0 mg/dL in women) or hyperkalemia (potassium ≥5.0 mEq/L) who are already receiving therapeutic doses of an ACE inhibitor, have an LVEF less than 40%, and have either symptomatic heart failure or diabetes. The Randomized Aldactone Evaluation Study treated patients with NYHA class III to IV heart failure with either spironolactone (25 to 50 mg daily) or placebo. Over 24 months of follow-up, spironolactone treatment was associated with an 11% absolute and a 24% relative risk reduction in all-cause mortality. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) randomized 6632 patients after MI with an LVEF of 40% or less and heart failure or diabetes to receive eplerenone (target dose, 50 mg daily) or placebo in conjunction with routinely indicated cardiac medications. There was a significant reduction in overall mortality, cardiovascular mortality, and cardiac hospitalizations.
Although hyperglycemia is associated with adverse outcomes after AMI, it is not clear that intensive glycemic control is associated with improved outcomes. Therefore, treatment for hyperglycemia greater than 180 mg/dL is recommended, while avoiding hypoglycemia.
Calcium Channel Blockers
It is reasonable to give verapamil or diltiazem to patients for whom β-blockers are ineffective or contraindicated (e.g., bronchospastic disease) for relief of ongoing ischemia or control of a rapid ventricular response with AF or flutter after STEMI in the absence of CHF, LV dysfunction, or AV block. There are no current data, however, to suggest that these agents decrease cardiac events. Nifedipine (immediate release) is generally contraindicated in the treatment of STEMI because of the reflex sympathetic activation, tachycardia, and hypotension associated with its use.
Use of a pulmonary artery catheter to measure hemodynamics in patients developing progressive CHF or hypotension may permit the early diagnosis of a preshock state in which aggressive pharmacologic support can prevent the onset of cardiogenic shock. Before PCI is performed for cardiogenic shock, the interventional cardiologist should insert a pulmonary artery catheter to maximize the hemodynamic status of the patient and to diagnose unrecognized mechanical complications. After reperfusion therapy, the pulmonary artery catheter may be used to guide diuretic, inotropic, and vasopressor agents in hemodynamically unstable patients while the stunned myocardium is recovering. Although no randomized clinical trial has tested whether hemodynamic monitoring alters clinical outcome in STEMI, one would expect that revascularization of ischemic myocardium would be required for outcomes to be improved.
Complications of pulmonary artery catheterization include ventricular tachyarrhythmias (during manipulation), pulmonary hemorrhage or infarction, and transient right bundle branch block, which can lead to heart block in those with preexisting LBBB. The catheter should not be inserted if the patient quickly responds to other interventions or if treatment is expected to be futile. The catheter should be expeditiously removed when it is no longer needed to monitor therapy or before 4 to 5 days because of risk of infection.
Hypotension (systolic BP pressure <90 mm Hg or 30 points below previous mean arterial pressure) can result from hypovolemia, arrhythmias, RV or LV failure, mechanical complications of MI, or superimposed complications such as sepsis or pulmonary embolism. Hypovolemia is a common occurrence and may be due to inadequate intake, diaphoresis and vomiting, overdiuresis, excessive use of vasodilators, or inappropriate reflex peripheral vasodilation. Hemorrhage is an increasingly common problem associated with the use of invasive procedures, fibrinolytics, antiplatelet agents, and anticoagulant agents. Therefore, rapid volume loading is recommended as an initial therapeutic strategy for all patients without clinical evidence for volume overload ( Figure 10-10 ). Persistent hypotension should be evaluated by echocardiogram to define the cardiac anatomy and a hemoglobin measurement. Correction or control of rhythm disturbances or conduction abnormalities often reverses hypotension. In patients with inotropic failure, vasopressors and inotropic agents are required. Dopamine or norepinephrine may be required for marked hypotension. There may be more arrhythmic events with dopamine than with norepinephrine. Once arterial pressure is brought to at least 90 mm Hg, IV dobutamine may be given simultaneously in an attempt to reduce the rate of the dopamine infusion. In addition, consideration should be given to initiating IABP counterpulsation or inserting an LV assist device.