Tirofiban and transfer compares favorably to fibrinolysis in STEMI

November 13, 2007 By Grendel Burrell [mailto:grendel.burrell@gmail.com]

Bialystok, Poland: The majority of STEMI patients presents to institutions without primary PCI. The treatment choices are rapid transfer to a tertiary centre for primary PCI or on-site fibrinolytic therapy. Guidelines emphasize that the time delay from symptom onset to treatment and the volume of procedures performed in PCI institution are critical factors in making a decision about the approach.

Investigators at the Medical University of Bialystok, Poland undertook a multi center, randomized, open-label study to compare fibrinolytic therapy at the community hospital to the strategy of transferring a patient with tirofiban to a PCI center (1). All patients were patients with standard criteria for STEMI within 12 hours of symptoms onset admitted to community hospitals without PCI capabilities. Patients were randomly assigned to either fibrinolytic therapy on site or to transfer to the PCI center with tirofiban. The randomization scheme accounted for gender, age, and location of MI.

401 patients presented to 13 hospitals within a 20-150 km range of Bialystok in the study. Patients with cardiogenic shock at presentation were excluded from the randomization and were immediately transferred for PCI.

All patients received 325 mg of aspirin. The patients assigned to PCI transfer for primary PCI received a 5000 IU IV dose of heparin and tirofiban (IV bolus of 10 mg/kg followed by infusion of 0.1 mg/kg/min) as soon as randomization had been completed. Tirofiban was continued during transportation, during PCI, and after the procedure. No additional heparin was given until arrival at the cath-lab, where, after ACT measurement before PCI, heparin was given only if needed to maintain the ACT at 300–350 seconds. Approximately 4 hours after the procedure, heparin was restarted to maintain APPT at 70 seconds. Tirofiban was continued for at least 8 hours post PCI. 75.7% of PCI patients received a stent and clopidogrel or ticlopidine were recommended.

For those patients randomized to fibrinolytic therapy, the choice of which fibrinolytic was decided by the hospital to which the patient presented. If streptokinase was used, LMWH was recommended. Heparin was utilized with fibrin-specific lytics. Rescue angioplasty was recommended in cases where there was no pain relief or no ST-segment resolution within 2 hours after the initiation of lytic therapy.

Randomized patients in both groups were very similar with respect to sex, age, SBP, history of hypertension or diabetes or dyslipidemia. However, the 4% of the group of patients treated wit h fibrinolytic therapy “on site” had a previous MI compared to 11.9% of the transfer group. There were more smokers in the on-site/fibrinolytic therapy group (P=0.027).

Most patients in both groups were admitted within 3 hours of symptom onset. 24.4% of the PCI-treated group waited <90 minutes from first medical contact to PCI.

2% of patients in each group experienced major bleeding. In the “on site” fibrinolytic therapy cohort, 3 patients experienced intracranial hemorrhage (1 fatality), and one patient required transfusion for gastrointestinal bleeding. In the PCI group, 3 patients were transfused for gastrointestinal bleeding, and one patient had fatal tamponade.

In hospital mortality was 8.5% in the fibrinolytic therapy group and 4.5% in the group transferred with tirofiban for PCI (P= 0.075). At 30 days, mortality in the fibrinolytic treated group was 9.0% compared to 5.0% for the PCI group (P=0.113). At 1-year follow up, the authors found a “trend toward lower mortality” in the transfer group (12.5% vs. 7.0%, P=0.061). Furthermore, at the 1-year follow up, the transfer/PCI group had a trend toward a lower incidence of re-AMI (7.5% vs. 3.5%, P=0.073).

The composite of death/re AMI/stroke was significantly higher in the on-site/fibrinolytic therapy group at the 30-day the follow up (15.5% vs. 8.0%, P=0.019), and again significantly higher at the 1-year follow up (21.5% vs. 11.4%, P=0.006). Patients in the transfer group also had a significantly reduced length of stay from 9.7+/-4.3 days to 14.1+/-5.5 days, P<0.0001.

At 30-day follow-up, 16.5% of patients in the thrombolytic group had experienced unscheduled catheterization. In the PCI group, 10 patients (4.97%) had required another catheterization (P=0.0002). At 1-year follow up, comparing the fibrinolytic therapy group to the PCI group, catheterization was performed in 43% vs. 13.4% of patients (P<0.0001), 28.5% vs. 11% of patients had PCI procedures (P<0.0001), and 6% of fibrinolytic therapy patients had coronary artery bypass surgery compared to 3% of patients in on-site group (P=0.145).

The authors previously executed an open label, non randomized, prospective study with tirofiban in 253 consecutive patients with STEMI and concluded that “In patients undergoing primary angioplasty for acute myocardial infarction the novel regimen of tirofiban is well tolerated and feasible, and is associated with improvement in coronary blood flow in the infarct related artery (2).”

In the current study the authors cite the TACTICS trial as providing some “evidence that the effect of tirofiban before invasive treatment was dependent o the length of the time of drug administration.” For this reason they chose tirofiban as an adjunctive treatment for the transferred cohort in this study. The authors also mention the “significantly lower” cost advantage of tirofiban compared with abciximab.

No patients in this study were pre-treated with clopidogrel. An additional potential limitation is that streptokinase was the main thrombolytics used. Unable to secure further funding for the study, the authors limited enrollment.

Not all patients present to PCI capable centers, and in this study, the authors have shown that transfer with tirofiban can offer advantages even when transport distances are as long as 150 km. The outcomes at 1-year follow up suggest that transport with tirofiban for PCI is superior to on site fibrinolytic therapy for patients with STEMI presenting to a hospital without PCI capabilities.

References:


 * 1) ref1 pmid=17884846


 * 1) ref1 pmid=15306748