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Double-blind, placebo-controlled phase II studies of E5555 in Japanese patients with Acute Coronary Syndrome (ACS) and Coronary Artery Disease (CAD)

Acute Coronary Syndromes (ACS)




Shinya Goto
  Presenter
Presenter | see Discussant report | read press release Webcasts become available 24 h after the presentation
Goto, Shinya
(Japan)
Open presentation slides

List of Authors:
Shinya Goto, Hisao Ogawa, Masaru Takeuchi, Marcus D. Flather, and Deepak L. Bhatt on behalf of the J-LANCELOT (Japanese – Lesson from Antagonizing the Cellular Effect of Thrombin) investigators

Abstract:

Introduction:
Two multicentre, randomised, double-blind, placebo-controlled Phase II studies assessed the safety and efficacy of the oral protease activated receptor 1 (PAR-1) antagonist E5555 in addition to standard therapy in Japanese patients with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD).

Patients with ACS (n=241) or high-risk CAD (n=263) received E5555 (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients) or 24 weeks (CAD patients). The incidence of TIMI major, minor, and minimal bleeds requiring medical attention was similar in the placebo and combined E5555 groups (ACS 6.6% placebo vs. 5.0% E5555; CAD 1.5% placebo vs. 1.5% E5555). There were no TIMI major bleeds and 3 CURE major bleeds (2 with placebo; 1 with 100 mg E5555). There was a numerical increase in “any” TIMI bleeding with the E5555 200 mg dose (ACS 16.4% placebo vs. 23.0% E5555, P=0.398; CAD 4.5% placebo vs. 13.2% E5555, P=0.081). The rate of MACE was numerically lower in the combined E5555 group than with placebo (ACS 6.6% placebo vs. 5.0% E5555, P=0.73; CAD 4.5% placebo vs. 1.0% E5555, P=0.066), but there was no significant difference. There was a statistically significant, dose-dependent increase in liver function abnormalities and QTcF with E5555. At trough dosing levels in both populations, mean inhibition of platelet aggregation was >90% with 100 mg and 200 mg E5555, and 20–60% with 50 mg E5555.

Conclusion:
E5555 (50, 100 and 200 mg) did not increase clinically significant bleeding, although there was a higher rate of any TIMI bleeding with the highest two doses. All doses tested achieved a significant level of platelet inhibition. There was a significant dose-dependent increase in liver function abnormalities and QTcF. Though further study is needed, PAR-1 antagonism may have the potential to be a novel pathway for platelet inhibition to add on to the current standard of care therapy.



Frans Van de Werf, FESC
  Discussant
Discussant | see Presenter abstract Webcasts become available 24h after the session
Van de Werf, Frans
(Belgium)
Open presentation slides

References


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SessionTitle:

Hot Line II - Coronary artery disease
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.