Tirofiban and eptifibatide are both small-molecule, competitive glycoprotein IIb/IIIa receptor inhibitors (GPIs) that are guideline-supported for upstream therapy in acute coronary syndromes (ACS). This study sought to compare the efficacy and safety of tirofiban and eptifibatide in patients with ACS.

Within the ACUITY trial, 4,323 patients with moderate- and high-risk ACS received upstream, adjunctive GPI (tirofiban or eptifibatide) in addition to an antithrombin. Primary outcomes included 30-day rates of composite major adverse cardiac events (MACE), major bleeding (not related to coronary artery bypass grafting), and composite net adverse clinical events (NACE). The outcomes were compared based on the upstream GPI administered.

There were significant differences in the baseline characteristics of patients treated with tirofiban vs eptifibatide, particularly related to country/region. In unadjusted analyses, treatment with upstream tirofiban vs eptifibatide was associated with similar rates of major bleeding (5.8% vs 6.5%, P = .39) and nonsignificantly lower rates of MACE (6.1% vs 7.6%, P = .06) and NACE (10.6% vs 12.6%, P = .06). After propensity-based multivariable adjustment, there were no significant differences between tirofiban and eptifibatide with respect to 30-day major bleeding, MACE, or NACE.

Among more than 4,000 patients with moderate- and high-risk ACS treated with upstream GPI as part of an early invasive management strategy, the use of tirofiban and eptifibatide resulted in similar clinical outcomes. These data suggest equivalence of these 2 agents for upstream use, while highlighting some of the difficulties of nonrandomized comparative effectiveness analyses, specifically the difficulty in addressing geographic differences in the use of nonrandomized treatments.