The CARESS study shows that patients with acute myocardial infarction admitted to a facility unable to perform angioplasty have better outcomes if transferred to an appropriate facility immediately after receiving thrombolytic therapy, according to a presentation at the annual meeting of the European Society of Cardiology.

The trial, conducted in Italy, Poland and France, involved various networks of community hospitals referring to a larger hospital for direct angioplasty of acute myocardial infarction. Patients were randomized with telephone allocation at the time of admission with all adverse events blindly reviewed by an independent Committee for adjudication and all electrocardiograms and angiograms analyzed by an independent Core Laboratory unaware of the treatment received.

The interval between administration of the thrombolytic drug and angioplasty was greater than 120 minutes in more than half of the patients (median, 136 minutes), which meant they were not candidates for primary angioplasty under current guidelines that require an interval of less than 90 minutes between first qualified medical contact and direct angioplasty.

The concern regarding thrombolysis before angioplasty was challenged by our finding of a low incidence of bleeding (0.8 percent intracranial hemorrhages and 2.9 percent bleeding episodes requiring 1 or more transfusions, with no difference between patients transferred for immediate angioplasty and patients who remained in the hospital of initial admission).

In our view, the lower rate of bleeding complications was due to the inclusion of patients at low risk of bleeding (patients less than 75 years old and well screened for contraindications to thrombolytics). We excluded older patients or patients with high bleeding risk from this trial because we believed in those cases it was more reasonable to pursue a less aggressive pharmacological strategy (for instance using only abciximab) or primary angioplasty.

Patients who were transferred and received angioplasty immediately after thrombolytics were much more likely (4.1 percent vs. 11.1 percent at 30 days) to be free from adverse events such as death, new myocardial infarction, new acute episode of chest pain, and electrocardiographic changes requiring urgent angioplasty.

This advantage was present despite the fact that all patients (36 percent of the entire conservative group) randomized to the group of more conservative treatment (no immediate transfer) were also promptly referred during the first hours post-treatment if there was no evidence that the lytic drugs had opened the occluded artery.

CARESS used a combination of the powerful intravenous anti-platelet agent abciximab and a reduced dose of the fibrin-specific lytic drug reteplase. This combination is very powerful and rapid in its action, with a synergistic effect demonstrated in previous trials and in in-vitro models, and achieved restoration of flow in the occluded artery in 85 percent of cases by the time patients reached the hospital where angioplasty was performed. Its main advantage is, however, the ability to inactivate platelets during the subsequent angioplasty, the opposite of the result observed when only lytics are given, which tend to activate platelets instead.

The authors conclude that the results should lead to a more liberal use of a strategy of facilitated angioplasty (that is, thrombolytics before angioplasty) when there is no certainty that the angioplasty can be performed within 90 minutes.