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Class I indicates treatment is useful and effective, IIa indicates weight of evidence is in favor of usefulness/efficacy, class IIb indicates weight of evidence is less well established, and class III indicates intervention is not useful/effective and may be harmful Type A recommendations are derived from large-scale randomized trials, and B recommendations are derived from smaller randomized trials or carefully conducted observational analyses ACC/AHA = American College of Cardiology/American Heart Association 2 As a class IIb, low-molecular-weight heparin (best studied is enoxaparin with tenecteplase) can be considered an acceptable alternative to unfractionated heparin for patients less than 75 years old who are receiving fibrinolytic therapy provided significant renal dysfunction is not present 3 For patients with persistent hypertension despite treatment, diabetes mellitus, congestive heart failure, or any left ventricular dysfunction 4 IA for patients with congestive heart failure or ejection fraction < 040, IIa for others, in absence of hypotension (systolic blood pressure < 100 mm Hg); angiotensin receptor blocker (valsartan or candesartan) for patients with ACE inhibitor intolerance 5 As early as possible before primary PCI 6 For patients with a low-density lipoprotein cholesterol level > 100 mg/dL

setting of acute coronary syndromes However, the SYNERGY trial showed that unfractionated heparin and enoxaparin had similar rates of death or (re)infarction in the setting of frequent early coronary intervention Fondaparinux, a specific factor Xa inhibitor given in a dose of 25 mg subcutaneously once a day, was found in the OASIS-5 trial to be equally effective as enoxaparin among 20,000 patients at preventing early death, myocardial infarction, and refractory ischemia, and resulted in a 50% reduction in major bleeding This reduction in major bleeding appeared to translate into a significant reduction in mortality (and in death and/ or myocardial infarction) at 30 days While catheter-related thrombosis was more common during coronary intervention procedures with fondaparinux, it appears that this can be controlled by adding unfractionated heparin during the procedure This trial not only established fondaparinux as an excellent treatment for acute coronary syndromes but also highlighted the importance of bleeding and its prevention The ACUITY trial showed that the direct thrombin inhibitor bivalirudin appears to be a reasonable alternative to heparin or enoxaparin plus a glycoprotein IIb/IIIa antag-

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onist for many patients with acute coronary syndromes who are undergoing early coronary intervention The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial demonstrated a 20% reduction in the composite end point of cardiovascular death, myocardial infarction, and stroke with the addition of clopidogrel (300 mg loading dose, 75 mg/d for 9 12 months) in patients with non ST-segment elevation acute coronary syndromes When treated with clopidogrel, the optimal aspirin dose appears to be 81 mg/d (versus 160 mg/d or 325 mg/d) based on similar thrombotic event rates and lower rates of bleeding Small molecule inhibitors of the platelet glycoprotein IIb/IIIa receptor are useful adjuncts in high-risk patients (usually defined by fluctuating ST-segment depression or positive biomarkers) with acute coronary syndromes, particularly when they are undergoing PTCA or stenting Tirofiban, 04 mcg/kg/min for 30 minutes, followed by 01 mcg/kg/min, and eptifibatide, 180 mcg/kg bolus followed by a continuous infusion of 01 mcg/kg/min, have both been shown to be effective when added to heparin Downward dose adjustments are required in patients with reduced renal function For example, if the estimated

creatinine clearance is below 50 mL/min, the eptifibatide infusion should be cut in half to 1 mcg/kg/min Fibrinolytic therapy should be avoided in patients without ST-segment elevation since they generally have a patent culprit artery, and since the risk of such therapy appears to outweigh the benefit

Intra-aortic balloon pump (IABP) counterpulsation can both reduce myocardial energy requirements (systolic unloading) and improve diastolic coronary blood flow This approach is sometimes used to stabilize patients prior to angiography or revascularization, but with modern techniques it is rarely necessary

FIGURE 1-4

The nitrates are first-line anti-ischemic therapy for acute coronary syndromes Nonparenteral therapy with sublingual or oral agents or nitroglycerin ointment is usually sufficient If pain persists or recurs, intravenous nitroglycerin should be started The usual initial dosage is 10 mcg/ min The dosage should be titrated upward by 10 20 mcg/ min (to a maximum of 200 mcg/min) until angina disappears or mean arterial pressure drops by 10% Careful usually continuous BP monitoring is required when intravenous nitroglycerin is used Avoid hypotension (systolic BP < 100 mm Hg) Tolerance to continuous nitrate infusion is common

Risk stratification is important for determining intensity of care Several therapies, including glycoprotein IIb/IIIa receptor antagonists, low-molecular-weight heparin, and early invasive catheterization, have been shown to have the greatest benefit in higher-risk patients As outlined in the ACC/AHA guidelines, patients with any high-risk feature (Table 10 5)

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