CHICAGO — The rate of major adverse cardiac events was roughly halved at 8 months by the use of sirolimus-eluting stents, compared with bare-metal stents in a randomized trial of 745 patients who underwent percutaneous coronary intervention for ST-segment elevation MI.
The Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs. Abciximab with Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study (MULTISTRATEGY) also found that tirofiban was noninferior to abciximab in resolving ST elevation at 90 minutes.
“These findings may provide a robust scientific rationale for high-dose tirofiban as an alternative to abciximab in patients with STEMI,” Dr. Marco Valgimigli said in a statement.
The open-label, 2-by-2 factorial trial showed that at 8 months, major adverse cardiac events (MACE) occurred in 29 of 372 patients (7.8%) treated with sirolimus-eluting stents and in 54 of 372 patients (14.5%) with bare-metal stents, Dr. Valgimigli reported on behalf of the MULTISTRATEGY investigators in a late-breaking clinical trial session at the Innovation and Intervention (i2) Summit. The difference was statistically significant.
The benefit was driven by a significant 69% relative risk reduction in target vessel vascularization from 10.2% to 3.2%.
Stent thrombosis was significantly lower in patients with sirolimus-eluting stents, regardless of which Academic Research Consortium definition was used, said Dr. Valgimigli, of the Cardiovascular Institute, University of Ferrara (Italy).
Results of the glycoprotein IIb/IIIa inhibitor arms of the study showed that tirofiban therapy was associated with a noninferior ST-segment resolution at 90 minutes following percutaneous coronary intervention when compared with abciximab.
In 722 patients with an interpretable ECG, at least 50% recovery from ST-elevation occurred in 308 of 361 (85.3%) patients in the tirofiban group and 302 of 361 (83.6%) patients in the abciximab group, according to Dr. Valgimigli's presentation and data published simultaneously online (doi:10.1001/jama.299.15.joc80026).
“Most importantly, these results proved to be consistent among multiple prespecified subgroups—including age, sex, diabetes, Killip class, stent type, number of diseased vessels, location of the infarction, time to treat the infarction—with no evidence of interaction between any of these groups and the study treatment,” Dr. Valgimigli said at the meeting, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.
Patient age was 64 years in the abciximab plus bare-metal stent (BMS) group, 63 years in the abciximab plus sirolimus-eluting stent (SES) group, 65 years in the tirofiban plus BMS group, and 63 years in the tirofiban plus SES group.
At 30 days, the incidence of MACE, death, or MI, and definite or definite/probable stent thrombosis, did not differ significantly between the two groups. However, the incidence of thrombocytopenia was significantly more common with abciximab.
At 8 months, there also was no significant difference between patients treated with tirofiban or abciximab in the incidence of MACE (9.8% vs. 12.4%), death or MI (6.2% vs. 7.3%), and target vessel revascularization (6.2% vs. 7.3%), said Dr. Valgimigli, who reported receiving honoraria and research support from Merck USA. The study was partially supported by Merck.
Discussant Dr. E. Magnus Ohman, professor of cardiovascular medicine, Duke Clinical Research Institute, in Durham, N.C., pointed out that the 25-mcg/kg bolus of tirofiban used in the trial with a standard 0.15-mcg/kg per minute infusion is much higher than the approved bolus dose of 10 mcg/kg. Americans have limited experience with this higher dose and with the drug in general, as it is used in less than 4% of percutaneous coronary intervention cases in the United States, he said.
He also said that that the study was underpowered for the clinical end points and that the rate of transfusion was numerically higher in the tirofiban group, “leaving open the issue of how safe is this higher dose of tirofiban studied in this trial.”
Dr. Ohman also questioned whether the 8-month follow-up on the stented patients was sufficient, given that late-stent thrombosis tends to occur after that period.
Regarding the tirofiban dose, Dr. Valgimigli said the investigators felt the 10-mcg bolus dosing was inadequate in patients with acute MI based on results of the TARGET trial, and that there is significant experience with the drug in Europe, where it is widely used. While bleeding is an important area of focus for practitioners, he said that very important data suggest that thrombocytopenia—which was significantly more common with abciximab than tirofiban—is an important clinical indicator as well.
Press briefing moderator Dr. William Knopf, chief operating officer at the Piedmont Heart Institute, Atlanta, said, “I think one of the most important things we learned from this trial is perhaps the correct dose of tirofiban that we can extrapolate into our patients.”