Pre-hospital administration of a high bolus dose (HBD) of tirofiban (Aggrastat, Iroko) in addition to aspirin, clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) and unfractionated heparin can reduce rates of major adverse cardiac events (MACE) in STEMI patients after primary PCI is performed, according to a study published May 25 in the Journal of the American College of Cardiology.
“Primary PCI has been shown to be the most effective treatment modality for restoring the blood flow in the infarct-related vessel,” the authors wrote. “Transporting patients to an intervention center, however, inevitably leads to a delay in initiation of the PCI and thus prolongs ischemic time.”
Jurriën M. ten Berg, MD, PhD, of the St. Antonius Hospital in Nieuwegein, the Netherlands, and colleagues conducted the two phase placebo-controlled, double-blind, randomized On-TIME 2 (Ongoing Tirofiban in MI Evaluation 2) clinical trial to assess the effectiveness of the GP IIb/IIIa receptor blocker, tirofiban and the outcomes of 1,398 STEMI patients after PCI.
While the phase 1 trial patients were randomized to receive either pre-hospital treatment of tirofiban or no tirofiban, patients in phase 2 received either tirofiban or placebo in addition to 500 gm of aspirin, 600-mg loading dose of clopidogrel and 5,000 IUs of heparin intravenously.
Researchers used rates of MACE—death, recurrent MI and target vessel revascularization—as primary endpoints and total rates of mortality after one year as the secondary endpoint of the study.
The researchers, over a three-year period, evaluated 1,398 patients: 414 patients during phase 1 of the trial and 984 patients during phase between June 2006 and November 2007.
“In both study phases, early HBD tirofiban treatment decreased the extent of residual ST-segment deviation and improved ST-segment resolution one hour after PCI as well as clinical outcome at 30 days and one year compared with placebo/no tirofiban treatment,” the authors wrote.
The researchers pooled the open-label and double-blind study phases and randomized 709 patients to HBD tirofiban and 689 patients to a placebo or no tirofiban infusion—96 percent of patients were randomized after pre-hospital diagnosis in the ambulance.
Researchers found that the median diagnosis time was 77 minutes while the median duration of transport to the nearest PCI center was 33 minutes—in 98.5 percent of patients, acute angiography was performed with a medium time of 20 minutes.
During the study, researchers found that 81 patients had false-positive STEMI diagnosis, five patients died before angiography and 16 patients did not undergo angiography due to a false-positive diagnosis. Additionally, initial TIMI flow grade 3 of the infarct-related artery was present in 22.5 percent of the tirofiban group compared to 19.4 percent in the placebo/no tirofiban group.
The rates of primary endpoints for the tirofiban group were 5.8 percent while these same rates for the placebo group were 8.6 percent. Additionally, rates of mortality were 2.2 percent in the tirofiban group compared to 4.1 percent in the placebo/no tirofiban group.
Incidence of major bleeding occurred in both groups, at a rate of 3.4 percent in the tirofiban group and 2.9 percent in the placebo/no tirofiban group. Stroke occurred at a rate of 0.3 percent and 1.4 percent for the tirofiban group and placebo group, respectively.
In a subgroup analysis of patients who presented early after the onset of symptoms, MACE rates were 4.5 percent in the tirofiban group and 8.5 percent in the placebo/no tirofiban group and TIMI flow grade 3 rates were 27.4 percent and 19.4 percent, respectively.
After one-year, data from 94 percent of patients was evaluated. Mortality rates for those in the tirofiban group were 3.7 percent compared to 5.8 percent in the placebo/no tirofiban group.
“Total mortality was lower in the pre-specified subgroup of patients who received HBD tirofiban within 75 minutes after the onset of symptoms (1.8 percent vs. 4.3 percent),” the authors wrote.
“This pooled analysis of the two phases of the On-TIME 2 trial showed that early initiation of HBD tirofiban, in addition to aspirin, heparin and high-dose clopidogrel, improved the clinical outcome at 30-day follow-up, with no significant increase in major bleeding,” said the authors.
According to the authors, results were slightly better in the group of patients who presented early and received tirofiban after the onset of symptoms