Atopaxar significantly reduced early ischemia on Holter monitoring (RR 0.67; P=0.02) without significantly increasing major or minor bleeding compared to placebo (3.08% vs 2.17%; P=0.63).
RCT (n=603)
Does atopaxar improve safety, tolerability, and early ischemia in patients with non-ST-elevation acute coronary syndromes?
In patients with non-ST-elevation ACS, atopaxar reduced early ischemia on Holter monitoring without significantly increasing bleeding, though higher doses were associated with transient transaminase elevation and QTc prolongation.
Absolute Event Rate: 3.08% vs 2.17%
p-value: p=0.63
BACKGROUND: Atopaxar (E5555) is a reversible protease-activated receptor-1 thrombin receptor antagonist that interferes with platelet signaling. The primary objective of the Lessons From Antagonizing the Cellular Effects of Thrombin-Acute Coronary Syndromes (LANCELOT—ACS) trial was to evaluate the safety and tolerability of atopaxar in patients with ACS. METHODS AND RESULTS: Six hundred and three subjects were randomized within 72 hours of non-ST-elevation ACS to 1 of 3 doses of atopaxar (400-mg loading dose followed by 50, 100, or 200 mg daily) or matching placebo. The incidence of Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) major or minor bleeding did not differ significantly between the combined atopaxar and placebo groups (3.08% versus 2.17%, respectively; P=0.63), and there was no dose-related trend (P=0.80). The incidence of CURE major bleeding was numerically higher in the atopaxar group compared with the placebo group (1.8% versus 0%; P=0.12). The incidence of cardiovascular death, myocardial infarction, stroke, or recurrent ischemia was similar between the atopaxar and placebo arms (8.03% versus 7.75%; P=0.93). The incidence of CV death, MI, or stroke was 5.63% in the placebo group and 3.25% in the combined atopaxar group (P=0.20). Dose-dependent trends for efficacy were not seen. Atopaxar significantly reduced ischemia on continuous ECG monitoring (Holter) at 48 hours compared with placebo (relative risk, 0.67; P=0.02). Transient dose-dependent transaminase elevation and relative QTc prolongation were observed with the highest doses of atopaxar. CONCLUSION: In patients after ACS, atopaxar significantly reduced early ischemia on Holter monitoring without a significant increase in major or minor bleeding. Larger trials are required to fully establish the efficacy and safety of atopaxar. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00548587.
O’Donoghue et al. (Tue,) conducted a rct in Acute Coronary Syndromes (n=603). Atopaxar vs. Placebo was evaluated on CURE major or minor bleeding (p=0.63). Atopaxar significantly reduced early ischemia on Holter monitoring (RR 0.67; P=0.02) without significantly increasing major or minor bleeding compared to placebo (3.08% vs 2.17%; P=0.63).
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