Acute Coronary Syndromes
This chapter describes the management of patients with acute, occlusive coronary artery thrombosis (acute coronary syndromes, or ACS). The importance of this disorder is shown by the claim that a fatal coronary event occurs once every minute in the United States (1). The focus of this chapter is on the early management of ACS, and not the diagnostic evaluation, and the recommendations are based on clinical practice guidelines from the American Heart Association (2,3).
I. Protective Measures
The following measures are aimed at protecting the myocardium from ischemic injury and limiting the extent of myocardial damage.
A. Oxygen Therapy
INDICATIONS: Oxygen therapy is recommended for an arterial O2 saturation <90%, and for patients with respiratory distress (2,3).
COMMENT: Supplemental O2 is no longer recommended as a routine measure in ACS because O2 promotes coronary artery vasoconstriction (4), and toxic O2 metabolites have been implicated in reperfusion injury (5). The potential for harm from O2 therapy was confirmed in a randomized study of patients with acute myocardial infarction in which patients who received supplemental
O2 developed larger infarctions and more frequent arrhythmias than patients allowed to breathe room air (6).
B. Nitroglycerin
INDICATIONS: Sublingual nitroglycerin (NTG) is recommended for immediate relief of ischemic chest pain. NTG is also given by continuous IV infusion for recurrent chest pain, hypertension, or decompensated heart failure associated with ACS.
DOSE: The sublingual dose of NTG is 0.4 mg, which can be repeated every 5 minutes for a total of 3 doses, if needed. The IV dose is a continuous infusion, starting at a rate of 5–10 μg/min, and titrating upward to achieve the desired effect. Dose rates above 100 μg/min are usually not necessary.
CONTRAINDICATIONS: NTG is not recommended for right ventricular infarction (because the venodilator effects of NTG are counterproductive), and in patients who have taken a phosphodiesterase inhibitor for erectile dysfunction within the past 24 hours (because of the risk of hypotension) (2,3).
NOTE: For more information on NTG, including adverse effects and NTG tolerance, see Chapter 45, Section V.
C. Morphine
INDICATIONS: Intravenous morphine is the drug of choice for ischemic chest pain that is refractory to nitroglycerin, and is also used for hydrostatic pulmonary edema (because of its venodilating and sedating effects).
DOSE: The effective dose of morphine can vary widely in individual patients. The initial dose is usually 4–8 mg as an IV bolus, followed by doses of 2–8 mg IV every 5 or 10 minutes, as needed (2,3).
NOTE: For information on the adverse effects of opioids, see Chapter 43, Section I-C.
D. Aspirin
INDICATIONS: Aspirin is an antiplatelet agent that is recommended for all patients with ACS who are not aspirin-sensitive or intolerant, and should be given as soon as possible (decreases mortality and re-infarction rate) (2,3).
DOSE: The initial dose is 162–320 mg, as a chewable tablet (enhances absorption), and the maintenance dose is 81 mg PO daily, using enteric-coated tablets (2,3).
E. β-Receptor Antagonists
INDICATIONS: β-receptor blockade is recommended for all patients with ACS who do not have a contraindication, and should be started within 24 hrs after presentation (2,3). Oral therapy is suitable for most cases; IV therapy is reserved for patients with persistent chest pain or troublesome tachycardia or hypertension.
CONTRAINDICATIONS: β-blockers are contraindicated in cases of high-grade AV block, decompensated systolic heart failure, hypotension, and reactive airway disease (2,3), and in cases of ACS associated with cocaine or amphetamine intoxication (risk of aggravated coronary vasospasm from unopposed β-receptor activity) (3).
DOSING REGIMENS: Metoprolol (a selective β1-antagonist) is a preferred β-blocker for ACS. The oral dosing regimen is 25–50 mg PO every 6 hrs for 48 hrs, then 100 mg PO BID for maintenance therapy. (Longer-acting
metoprolol succinate can be used for maintenance therapy at a dose of 200 mg once daily.) The IV dosing regimen is 5 mg as a bolus dose every 5 minutes, as tolerated, to a total of 3 doses (2).
F. RAA Inhibitors
Drugs that inhibit the renin-angiotensin-aldosterone (RAA) system include angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs).
INDICATIONS: ACE inhibitors are recommended for all cases of ACS that do not have a contraindication. They are especially beneficial in patients with anterior infarction or systolic dysfunction (ejection fraction ≤40%), and are recommended in the first 24 hrs after presentation in these patients (2). ARBs are reserved for patients who do not tolerate ACE inhibitors.
CONTRAINDICATIONS: These agents are contraindicated in patients with hypotension, bilateral renal artery stenosis, renal failure, or hyperkalemia.
DOSING REGIMENS: ACE inhibitors are given orally (risk of hypotension with IV ACE inhibitors post-MI), and several drugs can be used. One of the popular ACE inhibitors is lisinopril, which is started at a dose of 2.5 to 5 mg once daily, and gradually increased to 10 mg daily, as tolerated (2). For ACE inhibitor-intolerant patients the ARB valsartan has equivalent efficacy in acute MI (7). The initial dose is 20 mg PO BID, which is gradually increased to 160 mg PO BID, as tolerated (2).
G. Statins
INDICATIONS: High-intensity statin therapy is recommended for all cases of ACS that have been stabilized, including those with LDL cholesterol levels <70 mg/dL
(2,3). Of the available statins, only high-dose atorvastatin has a proven survival benefit in ACS (8).
COMMENT: The troublesome side effects of statins, such as myopathy and hepatotoxicity, occur with chronic therapy, and are not a concern when initiating statin therapy for ACS. There are drug interactions that de-serve mention; i.e., statins are metabolized by the cytochrome P450 system (CYP3A4), and drugs that inhibit this enzyme (e.g., amiodarone, omeprazole) can increase the risk of toxic reactions.
II. Reperfusion
A. The Approach
The fundamental goal in ACS is to relieve the obstruction and restore flow in the infarct-related coronary artery. There are three methods for achieving this goal: (a) percutaneous coronary intervention or PCI (coronary angiography, angioplasty, and stent placement), (b) thrombolytic therapy, and (c) coronary artery bypass surgery.
The approach to reperfusion is determined by the presence or absence of ST elevation on the ECG, as described next.
B. ACS with ST Elevation
ACS with ST elevation ≥0.1 mv in at least 2 contiguous leads usually indicates a transmural infarction, from complete obstruction of the infarct-related artery. This condition, ST-elevation myocardial infarction or STEMI, requires emergent intervention.
FIGURE 14.1 The survival benefit of thrombolytic therapy in relation to the time elapsed from the onset of chest pain. STEMI = ST-elevation myocardial infarction, LBBB = left bundle branch block. Data from Reference 9. |
1. Time-Dependence
There is convincing evidence that reperfusion with either PCI or thrombolytic therapy can restore flow in occluded arteries and decrease the mortality rate (2). However, the benefit from reperfusion therapy is time-dependent, and diminishes as the time progresses from the onset of chest pain. This is demonstrated in Figure 14.1 for thrombolytic therapy (9); note that the survival benefit is negligible after 12 hours from symptom onset.
2. Indications for Reperfusion Therapy
The major indications for reperfusion in patients with STEMI (or a new left bundle branch block) are as follows (2):
3. Percutaneous Coronary Intervention
Percutaneous coronary intervention (PCI) is superior to thrombolytic therapy for restoring flow in occluded arteries and improving outcomes (see Figure 14.2) (10,11,12). Unfortunately, PCI is not available in many hospitals. The recommendations for providing PCI to eligible STEMI patients (i.e., symptom onset <12 hrs, etc.) are as follows (2):