In the second study, led by Dr Gian B Danzi (Poliambulanza Hospital, Brescia, Italy), high-dose tirofiban (25 g/kg bolus followed by 0.15 g/kg per minute for 18 hours) was compared with a standard dose of abciximab in 102 patients undergoing primary coronary angioplasty. Again, all patients also received heparin. In this study, appearing in the July 1, 2004 issue of the American Journal of Cardiology, the primary end point was change in the infarct-zone wall-motion score index on echocardiography between initial exam and 30-day follow-up.2 The authors report that change in wall-motion score index was similar in the tirofiban- and abciximab-treated patients.

In both studies, there was no evidence of major bleeding, no need for red blood cell transfusions, and no episodes of severe thrombocytopenia.

"The results of the present study seem to confirm indirectly that the new dosing regimen of tirofiban leads to an optimal level of platelet inhibition, as shown by improvements in initial grades of TIMI flow and myocardial blush, which were similar to those observed in patients treated with abciximab," the authors conclude. "Although our data do not indicate whether improvements in TIMI scores (due to the combination of primary angioplasty and large-dose bolus of tirofiban) necessarily translate into better clinical outcomes, it is well known that myocardial blush grade best describes the effectiveness of myocardial reperfusion and is an independent predictor of long-term mortality rate."

Definitive answers on the role of tirofiban are anticipated from the TENACITY trial, an 8800-patient trial comparing tirofiban with abciximab in a factorial design that includes heparin and bivalirudin. "This will provide an important missing link in two ways," Dr Eric Topol (Cleveland Clinic, OH), who is heading up the TENACITY trial, commented to heartwire. "TENCACITY is using the upgraded and what appears to be optimal dosing of tirofiban and provides, for the first time, the opportunity to see whether the GP IIb/IIIa inhibitor and bivalirudin combination will be the ultimate best strategy." Bivalirudin, he added, may be especially helpful in reducing bleeding complications.

In the meantime, says Topol, the studies by the Danzi and Valgimigli groups "add support to the concept that the glitch in TARGET may have been due to suboptimal dosing of tirofiban."