Acute coronary syndromes: Therapy

Epidemiology

STEMI comprises approximately 25%–40% of ACS presentations, although more recent data show a decline in the percentage of ACS caused by STEMI between 1999 and 2008. ^, In-hospital mortality and 1-year mortality rates from STEMI have decreased significantly with improvements in reperfusion therapy and guideline-directed medical therapy (GDMT); current in-hospital mortality can be as low as 4%–6%, and 1-year mortality ranges from 7% to 18%. ^, Nonetheless, not all eligible patients with STEMI receive reperfusion therapy; registry data from 2017 estimated an overall early ECG miss rate of 7%, with the majority of those patients being elderly, and variability up to 30% between multiple large-volume emergency departments.

Women, people with diabetes, and patients with renal disease appear to have worse outcomes when presenting with STEMI. Approximately 23% of patients with STEMI in the United States have diabetes mellitus, and three-fourths of all deaths among patients with diabetes mellitus are related to coronary artery disease. Patients with chronic renal disease, particularly those on dialysis, are less likely to receive GDMT; only 45% of eligible patients on dialysis received reperfusion therapy, and only 70% received aspirin on admission. At discharge, only 67% of patients on dialysis were prescribed aspirin, and only 57% were prescribed beta-blockers. ^, Women and patients on dialysis tend to have higher bleeding complications associated with antithrombotic therapy. ^,

Diagnosis and treatment of STEMI

Symptoms suggestive of MI may be similar to those of ordinary angina but are typically greater in intensity and duration. Nausea, vomiting, and diaphoresis may be prominent features, and malaise and even stupor attributable to low cardiac output can occur. Compromised left ventricular function may result in pulmonary edema with the development of pulmonary bibasilar crackles and jugular venous distention; a fourth heart sound can be present with small infarcts or even mild ischemia, but a third heart sound is usually indicative of more extensive damage.

A consensus group to standardize the definition of MI defines the changes diagnostic of STEMI as new ST elevation at the J-point ≥1 mm (0.1 mV) in at least two contiguous leads, except leads V ₂ –V ₃ , where the threshold is higher (≥1.5 mm in women and ≥2 mm in men) or new left bundle branch block (LBBB). ^, The specificity of new LBBB has been challenged by a multicenter, longitudinal study published in which 4% of patients presenting with possible ACS had an LBBB presumed to be new, and of these, only 39% were diagnosed with ACS. Similar findings have been reported elsewhere. In the GUSTO-1 trial, of the 26,003 North American patients presenting with possible ACS, 131 (0.5%) with confirmed acute MI had an LBBB. A new or presumed new LBBB should not be considered diagnostic of acute MI in isolation, but when the clinical presentation strongly suggests ACS, and especially when shock is present, LBBB should be regarded as a STEMI equivalent.

Patients presenting with suspected myocardial ischemia should undergo a rapid evaluation, continuous monitoring, and reassessment. (See Fig. 70.1 for an algorithm for the initial evaluation and management of STEMI). The 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Guidelines for the Management of ST-Elevation Myocardial Infarction emphasize the importance of choosing some type of reperfusion therapy as soon as possible when appropriate. In addition to antiplatelet therapy, an early decision to perform percutaneous coronary intervention (PCI), transfer to a PCI-capable facility, or administer fibrinolytic therapy should be made. The timeliness of reperfusion is as important as the choice of therapy.

The preferred method for reperfusion in STEMI is PCI if it can be done in a timely manner, defined as the time from first medical contact (FMC) to device of less than 90 minutes. Emergency medical services (EMS) transport directly to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI. If a patient initially presents to a non–PCI-capable hospital and door in–door out time is anticipated to be less than 30 minutes, transfer to a PCI-capable hospital should be arranged if the FMC to device time is anticipated to be less than or equal to 120 minutes. If the FMC to device time is longer than 120 minutes, fibrinolytics should be considered, with probable transfer to a PCI-capable facility after fibrinolytic therapy for STEMI. Practical considerations regarding transport to a PCI-capable facility should be reviewed carefully before foregoing fibrinolytics for PCI.

Fibrinolytic therapy

Evidence from multiple clinical trials demonstrates the ability of fibrinolytic agents administered early in the course of an acute MI to reduce infarct size, preserve left ventricular function, and reduce short-term and long-term mortality. Patients treated early derive the most benefit.

Indications for and contraindications to fibrinolytic therapy are listed in Box 70.1 . Because of the small, but nonetheless significant, risk of bleeding complications (most notably, intracranial hemorrhage, which occurs in 0.7%–1.8% of high-risk patients treated with fibrinolytics), the selection of patients with acute MI for the administration of a fibrinolytic agent should be undertaken with prudence and caution. This is of special importance in intensive care unit (ICU) patients, who may have a predisposition to bleeding complications because of multiple factors. In this setting, emergent coronary angiography (with PCI as clinically indicated) is usually preferable.

Commonly administered fibrinolytics include the fibrin-specific agents tenecteplase, reteplase, and alteplase; the non–fibrin-specific agent streptokinase is infrequently used. After the administration of fibrinolytics for STEMI, the patient should be monitored for signs and symptoms of adequate reperfusion, as indicated by relief of symptoms and/or hemodynamic/electrical instability coupled with resolution of the highest initial ST elevation (preferably 50%, but at least some). Complete (or near-complete) ST segment resolution at 60 or 90 minutes after fibrinolytic therapy is a useful marker of a patent infarct artery. If signs of adequate reperfusion are not evident within 90 minutes (“failed fibrinolysis”), patients should be urgently transferred to a PCI-capable facility with intent to perform rescue PCI. In patients with clinically successful fibrinolysis, trial data suggest that death, recurrent MI, recurrent ischemia, new or worsening heart failure (HF), or shock at 30 days is reduced with routine angiography compared with patients who underwent an ischemia-guided approach, with the greatest benefit in high-risk patients. As such, in centers without angiographic capability, transfer to a PCI-capable facility after fibrinolytic therapy is recommended.

Patients with STEMI and signs of shock or severe HF should be immediately transferred to a PCI-capable facility irrespective of when the MI occurred or when fibrinolytics were given.

In contrast to the treatment of STEMI, fibrinolytics have shown no benefit and an increased risk of adverse events when used for the treatment of NSTE-ACS or UA. Based on these findings, there is currently no role for fibrinolytic agents in these latter syndromes.

Primary PCI in acute myocardial infarction

The major advantages of primary PCI over fibrinolytic therapy include a higher infarct artery patency with a higher rate of normal flow, lower rates of recurrent ischemia, reinfarction, the need for emergency repeat revascularization, and a lower risk of intracranial hemorrhage. ^, Placement of drug-eluting stents is now routine. ^, Coronary angiography also affords the ability to stratify risk based on the severity and distribution of coronary artery disease. Data from several randomized trials have indicated that PCI is preferable to fibrinolytic therapy for acute MI patients at a higher risk.

Achieving reperfusion in a timely manner correlates with improvement in the infarct size, left ventricular function, and survival. ^, The ultimate goal is to restore adequate blood flow through the infarct-related artery to the infarct zone and to limit microvascular damage and reperfusion injury. The latter is accomplished with adjunctive and ancillary treatments that are discussed later.

Previous clinical practice guidelines recommended against PCI of non–culprit artery stenoses at the time of primary PCI in patients with STEMI. Recent randomized controlled trials since this recommendation have demonstrated that multivessel PCI at the time of culprit artery PCI or as a staged procedure may be safe and beneficial. The largest of these trials was the COMPLETE study, which demonstrated a significant decrease in a composite outcome of cardiovascular (CV) death or MI in those patients with complete revascularization. Given these findings, PCI of a non-culprit vessel may be considered either at the time of primary PCI or as a staged procedure in patients presenting with a STEMI. ^, In patients with cardiogenic shock, however, multivessel PCI was not shown to be effective, and so this is not recommended in this setting.

Coronary artery bypass graft surgery in patients with STEMI

Subsets of patients who present with STEMI are better served with coronary artery bypass graft (CABG) surgery. Patients with failed PCI or whose coronary anatomy is not amenable to PCI but who have ongoing symptoms of ischemia, cardiogenic shock, severe HF, or other high-risk features should be considered for CABG. CABG is also recommended in patients who require not only revascularization but also the repair of a mechanical defect, such as a ventricular septal defect, free wall rupture, or papillary muscle rupture. The previously reported increased mortality in CABG patients who recently had a STEMI needs to be balanced against the need for revascularization. Consideration must be given to the timing of urgent CABG in relation to the administration of antiplatelet agents in patients with a recent STEMI. Table 70.1 provides a summary of these recommendations. The risk of major bleeding and mediastinal re-exploration is higher in patients on dual antiplatelet therapy, but if therapy can be held for 3–5 days, the magnitude of this risk is uncertain. ^, The risk of postoperative bleeding may be higher in patients previously given prasugrel.

TABLE 70.1

Timing of Urgent Coronary Artery Bypass in Patients With ST Elevation Myocardial Infarction in Relation to the Use of Antiplatelet Agents

Adapted from O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guidelines for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation . 2013;127:e362–e425.

CABG, Coronary artery bypass grafting; COR, class of recommendation; LOE, level of evidence.

Adjunctive therapy