In the analysis by Keeley and Grines of 23 randomized studies comparing PCI with thrombolytic therapy in AMI, primary PCI was better than thrombolytic therapy at reducing overall short-term death (7% vs. 9%; P = 0.0002), nonfatal reinfarction (3% vs. 7%; P <0.0001), stroke (1% vs. 2%; P = 0.0004), and the combined endpoint of death, nonfatal reinfarction, and stroke (8% vs. 14%; P <0.0001) (1). These results remained in favor of PCI during long-term follow-up and were independent of both the type of thrombolytic agent used and whether or not the patient was transferred for primary PCI. At our institution, all patients with ST-elevation MI (STEMI) <12 hours receive primary PCI.

Studies that evaluated transfer to centers where primary PCI could be performed demonstrated superiority of mechanical versus pharmacological reperfusion. To date five trials have randomized STEMI patients to transfer for primary PCI versus lytic therapy. The PRAGUE 1 study (300 patients) compared three strategies in patients with AMI <6 hours from onset: (a) thrombolysis in the hospital, (b) thrombolysis during transfer for facilitated PTCA, and (c) transportation to a center for primary PTCA without thrombolytic treatment. The primary end point of death, reinfarction, and stroke at 30 days was less frequent in the transfer for PCI group (8%) compared to the second (15%) and first (23%; P <0.02). The incidence of reinfarction was significantly reduced by transportation for PCI (4). In the PRAGUE 2 study, 850 patients with AMI <12 hours were randomized to transfer for primary PCI (<120 km) versus on-site thrombolysis in the original hospital. The study ended prematurely due to excess mortality in the subgroup, which presented with ≥3 hours of symptoms, and overall 30-day mortality was 6.8% for the angioplasty group and 10% for thrombolysis group (P = 0.12). Complications only occurred during transfer (1.2%). The combined end point was less frequent in the PCI group (P <0.003), with more stroke in the thrombolysis group (P = 0.03) (3). The DANAMI 2 study compared on-site thrombolytic treatment with transfer to another center for PCI and again was stopped prematurely due to more PCI benefit. There were no deaths during transfer, and there was a 75% reduction in the relative risk of reinfarction (P = 0.0003) and decreased major adverse cardiac events (MACE) at 30 days (P = 0.02) in the PCI group. Primary PCI was of benefit in the different groups, including inferior or anterior infarctions and regardless of the time from symptom onset to intervention (2). Mean time from symptom onset to randomization was 135 minutes. In Figure 12-2, our recommendations to improve transfer and reperfusion time are listed.

The use of aspirin prior to primary PCI is unequivocal and should be given to all patients unless a true allergy exists (20). We provide patients with four tablets of chewable baby aspirin, which is more effective than 81 mg alone, and we avoid the enteric coated form for more rapid delivery of the drug.

The HEAP study did not support the use of heparin as pretreatment for angioplasty (21). However, heparin is routinely initiated in the ED intravenously at a dose of 70 units/kg prior to arrival to the cardiac catheterization laboratory.

A recent meta-analysis of the studies involving GP IIb/IIIa inhibitors in patients with ST segment elevation AMI (11 trials, involving 27,115 patients) demonstrated that when compared with the control group, abciximab was associated with a significant reduction in short-term (30 days) mortality (2.4% vs. 3.4%, P = 0.047) and long-term (6 to 12 months) mortality (4.4% vs. 6.2%, P = 0.01). This was observed in patients undergoing primary PCI but not in those treated with fibrinolysis or in all trials combined. Abciximab was associated with a significant reduction in 30-day reinfarction, both in all trials combined (2.1% vs. 3.3%, P <0.001), in primary angioplasty (1.0% vs. 1.9%, P = 0.03), and in fibrinolysis trials (2.3% vs. 3.6%, P <0.001). Abciximab did not result in an increased risk of intracranial bleeding (0.61% vs. 0.62%, P = 0.62) overall, but was associated with an increased risk of major bleeding complications when combined with fibrinolysis (5.2% vs. 3.1%, P <0.001) (22). In our institution, abciximab is frequently given for ST-segment elevation AMI in the absence of contraindications. Some operators administer the abciximab bolus intracoronary. Because few data exist regarding the use of small molecular weight GP IIb/IIIa inhibitor agents in AMI, we do not advocate the use of eptifibatide or tirofiban for STEMI.

Thrombolytics are occasionally administered prior to PCI either as a failed primary revascularization protocol (rescue PCI) or as a facilitative modality in an attempt to enhance pre-PCI TIMI flow (facilitated PCI). Three recent trials, MERLIN (23), REACT (24), and STOPAMI (25), suggested greater myocardial salvage and fewer MACE with rescue PCI compared to conservative therapy. Despite multiple recent trials CAPITAL AMI (26), BRAVE (27), ON-TIME (28), and GRACIA-1 (29), to date no trial has shown that facilitated PCI is superior to primary PCI alone. In fact, no trial has shown clinical benefit, and some trials have suggested harm. The largest trial to date, ASSENT-4, was stopped prematurely due to increased deaths, reinfarction, and MACE in the facilitated arm compared to primary PCI. Although, the AHA/ACC guidelines allowed facilitated PCI as a class IIb recommendation in high-risk patients where PCI will be delayed and there is a low risk of complications due to bleeding (15), given the data from recent trials showing harm, we do not recommend facilitation with thrombolytics. The use of GP IIb/IIIa inhibitors does not appear to cause harm, but these should not be used if their administration will delay transfer to the cath lab. This may be particularly a problem with the complex dosing regimens required for eptifibatide.

In patients 75 years of age or younger who have AMI with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel was found to improve the patency rate of the infarct-related artery and reduce ischemic complications (30). Moreover, in the recent mega trial (COMMITT) that included over 40,000 patients with STEMI who were randomized to clopidogrel versus placebo, there was a decrease in the incidence of death and the composite incidence of death/MI/stroke with the use of clopidogrel for up to 4 weeks postdischarge. There was no increase in the incidence of major bleeding with the use of clopidogrel (31). However, it should be kept in mind that the preoperative use of clopidogrel in patients undergoing coronary artery bypass graft (CABC) surgery has been shown to be associated with a significantly increased risk of bleeding and blood transfusion (32). Because 90% of patients with STEMI who go to the cath lab will undergo primary PCI and, in our experience, virtually no patients with STEMI will undergo CABG in the first few days, we recommend 600-mg loading dose of clopidogrel in the EC. The higher dose provides more rapid onset of action and more complete platelet inhibition. We usually continue clopidogrel for 9 to 12 months based on the results from the CURE (33) and CREDO trials (34).