Early Therapy
Key Points:
- Patients whose chest pain symptoms are suggestive of serious illness need immediate assessment in a monitored area of the ER and early therapy to include an IV, oxygen, aspirin, nitroglycerin, and morphine.
- Early therapy may consist of: aspirin, heparin or low molecular weight heparin, nitrates, beta blockers, and clopidogrel.
Aspirin (ASA) reduces mortality, reinfarction, and stroke. Although the incremental value of heparin/low-molecular weight heparin (LMWH) in conjunction with aspirin and reperfusion therapy is controversial, it does appear to enhance patency, and was included in the GUSTO protocol. In eligible patients, beta-blockers reduce mortality, reinfarction, and stroke. Although long-acting nitrates (oral and intravenous) appeared to reduce mortality in trials that did not include thrombolysis, more recent studies that did include thrombolysis found no incremental benefit from nitrate therapy. Nitrate therapy is still appropriate for ischemic pain relief.
All patients should receive aspirin (chewable) as soon as possible and continued indefinitely. In those patients who are unable to take aspirin, clopidogrel should be considered in hospitalized patients. If the probability of urgent coronary artery bypass graft (CABG) is low, consider early use of clopidogrel. The benefits of beta-blockers, nitroglycerin, and heparin are well established. There is data to support the use of LMWH as an alternative to intravenous heparin.
In high-risk patients, early administration of subcutaneous LMWH (enoxaparin 1mg/kg subcutaneous every 12 hours) or IV unfractionated heparin (UFH) (70 units/kg load then 12 to 15 units/kg/hr to achieve activated partial thromboplastin time [aPTT] levels of 1.5 to 2.5 times the control), with aspirin and/or clopidogrel is associated with a decrease in the incidence of AMI and ischemia.
LMWH, specifically enoxaparin, has been shown to have a moderate benefit over IV heparin in decreasing the rate of death, myocardial infarction (MI), and recurrent ischemia. A meta-analysis of the 2 trials showed a statistically significant reduction by 20% in the rate of death and MI.
LMWH should be used with caution in patients with renal insufficiency.
The recently completed SYNERGY study found increased adverse events in patients that were switched from unfractionated heparin to low-molecular weight heparin or vice-versa at the time of referral to tertiary care institutions. Therefore, the suggestion is that the patient be started and maintained on one drug or the other during transfer and treatment at referring and referral institutions.
Beta-blockers should be initiated early in the absence of any contraindications. In high-risk patients, they should be given initially IV, then followed by the oral route with a goal target resting heart rate of 50 to 60 beats per minute (bpm). Patients with low to intermediate risk may start out with oral therapy. The duration of benefit is uncertain. A meta-analysis of double blinded randomized trials in patients with evolving MI showed a 13% reduction in risk progression to AMI. Other multiple randomized trails in coronary artery disease (CAD) patients have shown a decrease in mortality and/or morbidity rates.
Beta-blockers should be used in most patients with STEMI. They remain underutilized in patients with chronic obstructive pulmonary disease (COPD) and diabetes mellitus where definite benefit has been demonstrated. Beta-blockers are relatively contraindicated in patients with asthma and hypotension, less so with first degree atrioventricular (AV) block, heart rate less than 60/min, or decompensated congestive heart failure (CHF). They should be used cautiously, if at all in these conditions. They should be completely avoided in STEMI due to cocaine use because of the risk of exacerbating coronary spasm, and in patients with cardiogenic shock.
Nitroglycerin should be given sublingually (0.4 mg every five minutes) to relieve ischemic symptoms. If symptoms are ongoing or recurrent despite the administration of IV beta-blockers, IV nitroglycerin can be initiated at 10 mcg/min and titrated every 3 to 5 minutes by 10 mcg/min until symptom response is noted or blood pressure decreases to less than 110 mmHg in patients previously normotensive or by 25% in patients who were hypertensive on presentation, or to a maximum dose of 200 mcg/min. Patients can be converted to topical or oral nitrates once stabilized (no manifestations of ischemia and pain free for 12 to 24 hours).
ISIS-4 and GISSI-3 failed to show a benefit of nitroglycerin on reduction of mortality in AMI.
Nitroglycerin is contraindicated in patients who are hypotensive, have documented severe aortic stenosis, have hypertrophic cardiomyopathy, or who have received sildenafil, vardenafil, or ordenafil within the previous 24 hours or tadalafil in the previous 48 hours.
GPIIb/IIIa Inhibitors
Patients with high risk or patients with intermediate risks and diabetes as defined in Annotation #27 "Risk Assessment (ACC/AHA Criteria)," benefit from receiving GP IIb-IIIa inhibitor (Tirofiban HCl, abciximab, or Eptifibatide) as part of initial treatment.
Early invasive strategy involves diagnostic catheterization within 24 to 48 hours, followed by PCI or CABG if warranted.
Contraindications to IIb-IIIa inhibitors include bleeding less than six weeks, intracranial hemorrhage (ever), recent stroke less than 2 years, uncontrolled hypertension greater than 200/100 mm Hg, surgery less than six weeks, aortic dissection, acute pericarditis, and platelets less than 100,000 mm3.
Evidence supporting this recommendation is of classes: A, C, M, R