Editorial

Timeliness of treatment is more important than choice of reperfusion therapy

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Reperfusion therapy decreases morbidity and mortality rates in patients with ST-segment elevation myocardial infarction (MI). Primary percutaneous coronary intervention (PCI) is preferred over fibrinolytic therapy as a reperfusion strategy when the delay in the time to treatment is short and the patient presents to a high-volume, well-equipped center with expert interventional cardiologists.

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Compared with fibrinolytic therapy in randomized clinical trials, primary PCI produces higher rates of infarct artery patency, complete reperfusion (grade 3 by the criteria of the Thrombolysis in Myocardial Infarction [TIMI] study), and access-site bleeding. It also produces lower rates of recurrent ischemia, reinfarction, emergency repeat revascularization procedures, intracranial hemorrhage, and death.1 If performed early and successfully, primary PCI also greatly decreases the rates of complications of ST-elevation MI that result from longer ischemic times or unsuccessful fibrinolytic therapy, allowing earlier hospital discharge and resumption of daily activities. Primary PCI is also the best reperfusion option in patients who present late after the onset of symptoms and in patients with cardiogenic shock, and it is the only option in patients who have contraindications to fibrinolytic therapy because of bleeding risk.

However, most hospitals do not have PCI capability. Two options at these hospitals are to transfer the patient to a PCI center quickly for primary PCI or to keep the patient on site and give fibrinolytic therapy, with its limitations. Earlier trials suggested that the transfer strategy was superior, but they had limitations: most patients received streptokinase, an inferior fibrinolytic agent, and door-to-door-to-balloon times were rapid, averaging only 95 minutes because of excellent logistical protocols and careful patient selection.2 Most importantly, rescue PCI and routine PCI were seldom performed in patients receiving fibrinolytics, so fibrinolytic therapy was being tested as monotherapy.

In the real world, however, treatment delays are much longer, and fibrinolytic therapy has evolved into a strategy that includes crossover to rescue PCI or routine PCI. Therefore, the initial trials of transfer for primary PCI do not reflect current practice. In fact, recent registry data suggest that prehospital fibrinolytic therapy followed by early angiography is superior to primary PCI because most patients can be treated within 2 hours of symptom onset; they also suggest that on-site fibrinolytic therapy followed by early angiography is equal in efficacy to primary PCI as long as rescue PCI and routine PCI can be performed.3,4

The most important modifiable predictor of outcome in ST-elevation MI is the time to treatment, a biological truth that continues to be supported by clinical evidence despite ideologic arguments by some interventional cardiology enthusiasts who claim that primary PCI is always superior to the fibrinolytic strategy, regardless of delays.

SURPRISINGLY, OUTCOMES WERE WORSE WITH FACILITATED PCI

It made sense, then, to conclude that the perfect strategy for hospitals without PCI capability would be a combined strategy of immediate fibrinolytic therapy to decrease the time delay associated with organizing PCI, and rapid transfer for immediate PCI to improve the limited reperfusion rates associated with fibrinolytic therapy.

Surprisingly, though, randomized trials found worse outcomes with this “facilitated PCI” strategy.5

Again, limitations in trial design might explain the lack of benefit in the trials. Inadequate anticoagulant and antiplatelet therapy were given to the fibrinolytic patients, and primary PCI patients had relatively short treatment delays, with many patients enrolled at hospitals with PCI capability.

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