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Streptokinase is not commonly used for treatment of acute myocardial infarction since it is less effective at opening occluded arteries and less effective at reducing mortality It is non-fibrin-specific, causes depletion of circulating fibrinogen, and has a tendency to induce hypotension, particularly if infused rapidly This can be managed by slowing or interrupting the infusion and administering fluids There is controversy as to whether adjunctive heparin is beneficial in patients given streptokinase, unlike its administration with the more clot-specific agents Allergic reactions, including anaphylaxis, occur in 1 2% of patients, and this agent should generally not be administered to patients with prior exposure Alteplase (recombinant tissue plasminogen activator; tPA) is a naturally occurring plasminogen activator that is modestly fibrin specific, resulting in about a 50% reduction in circulating fibrinogen In the first GUSTO trial, which compared t-PA (with unfractionated heparin) with streptokinase, the 30-day mortality rate with t-PA was one absolute percentage point lower (one additional life saved per 100 patients treated), though there was also a small increase in the rate of intracranial hemorrhage An angiographic substudy confirmed a higher 90-minute patency rate and a higher rate of normal (TIMI grade 3) flow in patients Reteplase is a recombinant deletion mutant of t-PA that is slightly less fibrin specific In comparative trials, it appears to have efficacy similar to that of alteplase, but it has a longer duration of action and can be administered as two boluses 30 minutes apart Tenecteplase (TNK-t-PA) is a genetically engineered substitution mutant of native t-PA that has reduced plasma clearance, increased fibrin sensitivity, and increased resistance to plasminogen activator inhibitor-1 It can be given as a single weight-adjusted bolus In a large comparative trial, this agent was equivalent to t-PA with regard to efficacy and resulted in significantly less noncerebral bleeding 1 Selection of a thrombolytic agent In the United States, most patients are treated with alteplase, reteplase, or tenecteplase The differences in efficacy between them are small compared with the potential benefit of treating a greater proportion of appropriate candidates in a more prompt manner The principal objective should be to administer a thrombolytic agent within 30 minutes of presentation or even during transport The ability to administer tenecteplase as a single bolus is an attractive feature that may facilitate earlier treatment The combination of a reduced-dose thrombolytic given with a platelet glycoprotein IIb/IIIa antagonist has been investigated in several trials, with no evidence of reduction in mortality but a modest increase in bleeding complications 2 Postthrombolytic management After completion of the thrombolytic infusion, aspirin (81 325 mg/d) should be continued Anticoagulation with intravenous heparin (initial dose of 60 units/kg bolus to a maximum of 4000 units, followed by an infusion of 12 units/kg/min to a maximum of 1000 units, then adjusted to maintain an activated partial thromboplastin time [aPTT] of 50 75 seconds beginning with an aPTT drawn 3 hours after thrombolytic) is continued for at least 24 hours after alteplase, reteplase, or tenecteplase.

Immediate coronary angiography and primary PCI (including stenting) of the infarct-related artery have been shown to be

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superior to thrombolysis when done by experienced operators in high-volume centers with rapid time from first medical contact to intervention ( door-to-balloon ) US and European guidelines call for first medical contact or door-toballoon times of < 90 minutes Several trials have shown that if efficient transfer systems are in place, transfer of patients with acute myocardial infarction from hospitals without to hospitals with primary PCI capability can improve outcome compared with thrombolytic therapy at the presenting hospital, although this requires sophisticated systems to ensure rapid identification, transfer, and PCI Primary PCI is the approach of choice in patients with absolute and many relative contraindications to thrombolytic therapy The results of this approach in specialized centers are excellent, exceeding those obtainable by thrombolytic therapy even in good candidates, but this experience may not be generalizable to centers and operators with less experience or expertise Stenting in conjunction with the platelet glycoprotein IIb/IIIa antagonist abciximab is now widely used in patients with acute myocardial infarction In the subgroup of patients with cardiogenic shock, early catheterization and percutaneous or surgical revascularization are the preferred management Because an acute interventional approach carries a lower risk of hemorrhagic complications, it may also be the preferred strategy in many older patients (see Tables 10 4 and 10 5 for factors to consider in choosing thrombolytic therapy or primary PCI) In part because patients in the United States who are transferred for primary PCI tend to have long delays from first hospital arrival to balloon inflation, there has been interest in developing facilitated PCI whereby a combination of medications (full or reduced dose fibrinolytic agents with or without glycoprotein IIb/IIIa inhibitors) is given to establish patency followed by immediate PCI While this approach has been shown to establish patency at the time of catheterization laboratory arrival in a substantial portion of patients, it has not yet been shown to improve outcome In fact, in the ASSENT-4 PCI trial, patients with a delay in median time to PCI balloon inflation did better if they did not receive full-dose tenecteplase on the way to the catheterization laboratory Thus, for the time being, patients should be treated either with fibrinolytic agents (and immediate rescue PCI for reperfusion failure) or with primary PCI, if it can be done in the rapid timecourse outlined in the ACC/ AHA guidelines.

after two or three tablets, intravenous opioids provide the most rapid and effective analgesia and may also reduce pulmonary congestion Morphine sulfate, 4 8 mg, or meperidine, 50 75 mg, should be given Subsequent small doses can be given every 15 minutes until pain abates

Although trials have shown modest short-term benefit from intravenous -blockers given immediately after acute myocardial infarction, it has not been clear that this provides a major advantage over simply beginning an oral blocker The Chinese COMMIT/CCS-2 trial involving 45,000 patients found no overall benefit to intravenous followed by oral metoprolol; the aggressive dosing (three 5 mg intravenous boluses followed by 200 mg/d orally) appeared to prevent reinfarction at the cost of increasing shock in patients presenting with heart failure Thus, blockade should be avoided in patients with decompensated heart failure, decompensated asthma, or high degrees of AV block The CAPRICORN trial showed the benefits of carvedilol following the acute phase of large myocardial infarction with contemporary care

Nitroglycerin is the agent of choice for continued or recurrent ischemic pain and is useful in lowering BP or relieving pulmonary congestion However, routine nitrate administration is not recommended, since no improvement in outcome has been observed in the ISIS-4 or GISSI3 trials, in which a total of over 70,000 patients were randomized to nitrate treatment or placebo Nitrates should be avoided in patients who received phosphodiesterase inhibitors (sildenafil, vardenafil, and tadalafil) in the prior 24 hours

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