Author + information
- Received October 28, 2019
- Accepted November 20, 2019
- Published online February 10, 2020.
- Usman Baber, MD, MSa,∗,
- M. Urooj Zafar, MBBSb,∗,
- George Dangas, MD, PhDa,
- Ginés Escolar, MD, PhDb,
- Dominick J. Angiolillo, MD, PhDc,
- Samin K. Sharma, MDa,
- Annapoorna S. Kini, MDa,
- Samantha Sartori, PhDa,
- Lauren Joyce, BAa,
- Birgit Vogel, MDa,
- Serdar Farhan, MDa,
- Paul Gurbel, MD, PhDd,
- C. Michael Gibson, MDe,
- Valentin Fuster, MD, PhDa,
- Roxana Mehran, MDa,∗ (, )@Drroxmehran and
- Juan J. Badimon, PhDb
- aCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- bAtherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, New York, New York
- cDivision of Cardiology, University of Florida College of Medicine, Jacksonville, Florida
- dInova Center for Thrombosis Research and Translational Medicine, Falls Church, Virginia
- eCardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Roxana Mehran, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, New York 10029.
Background An evolving strategy in the setting of percutaneous coronary intervention (PCI) involves withdrawal of acetylsalicylic acid (ASA), or aspirin, while maintaining P2Y12 inhibition. However, the pharmacodynamic effects of this approach on blood thrombogenicity and platelet reactivity remain unknown.
Objectives This study sought to compare the antithrombotic potency of ticagrelor alone versus ticagrelor plus ASA among high-risk patients undergoing PCI with drug-eluting stents.
Methods This was a mechanistic substudy within the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, which randomized patients undergoing PCI to ticagrelor plus placebo versus ticagrelor plus ASA following 3 months of dual antiplatelet therapy. Substudy participants were enrolled after randomization, at which time ex vivo assays to quantify thrombus size under dynamic flow conditions and platelet reactivity were performed. Pharmacodynamic assessments were repeated 1 to 6 months thereafter. The primary endpoint was thrombus size at the post-randomization visit with platelet reactivity following stimuli to arachidonic acid, collagen, adenosine diphosphate, and thrombin as secondary endpoints. Results were analyzed using analysis of covariance.
Results A total of 51 patients were enrolled, among whom 42 underwent perfusion assays at baseline and follow-up with a median time between studies of 1.5 months. The adjusted mean difference in post-randomization thrombus area was similar between groups: −218.2 μm2 (95% confidence interval [CI]: −575.9 to 139.9 μm2; p = 0.22). Markers sensitive to cyclo-oxygenase-1 blockade, including platelet reactivity in response to arachidonic acid (mean difference: 10.9 U; 95% CI: 1.9 to 19.9 U) and collagen (mean difference: 9.8 U; 95% CI: 0.8 to 18.8 U) stimuli were higher among patients receiving placebo, whereas levels of platelet reactivity were similar with adenosine diphosphate and thrombin.
Conclusions Among high-risk patients receiving drug-eluting stents, the antithrombotic potency of ticagrelor monotherapy is similar to that of ticagrelor plus ASA with respect to ex vivo blood thrombogenicity, whereas markers sensitive to cyclo-oxygenase-1 blockade are increased in the absence of ASA. (Platelet Substudy of the TWILIGHT Trial; NCT04001374).
↵∗ Drs. Baber and Zafar contributed equally to this manuscript.
The TWILIGHT study was funded by AstraZeneca. Dr. Baber has received an institutional research grant from AstraZeneca; and has received personal fees from Amgen, AstraZeneca, and Boston Scientific. Dr. Dangas has received consulting fees from GE HealthCare, Janssen Pharmaceuticals, Inc., and Medtronic, Inc.; has <1% equity with Claret Medical and Elixir Medical; has delivered industry-sponsored lectures for The Medicines Company; and is on the Scientific Advisory Board of AstraZeneca. Dr. Angiolillo has received grants and personal fees from AstraZeneca, Amgen, Aralez, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Janssen Pharmaceuticals, Merck & Co., Inc., Sanofi, and CeloNova; has received personal fees from Haemonetics, PhaseBio, PLx Pharma, Pfizer, The Medicines Company, and St. Jude Medical; has received grants from CSL Behring, Eisai, Gilead, Idorsia Pharmaceuticals Ltd., Matsutani Chemical Industry Co., Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation; and has received National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational Science Award UL1 TR000064 to the University of Florida, and National Institutes of Health/National Human Genome Research Institute grant U01 HG007269. Dr. Sharma has served on the Speakers Bureau of Abbott Vascular, Boston Scientific, and Cardiovascular Systems, Inc.; and the Scientific Advisory Board of Boston Scientific. Dr. Gurbel has received grants from National Institutes of Health, Bayer, Medicure, Instrumentation Labs, US WorldMeds, Haemonetics, Amgen, Idorsis, Ionis, Janssen Pharmaceuticals, and Merck & Co., Inc.; has received personal fees from Bayer, Merck & Co., Inc., UpToDate, Medicure, and US WorldMeds; and holds a patent in the area of personalized antiplatelet therapy and interventional cardiology. Dr. Gibson has received grants and personal fees from Johnson & Johnson, Janssen Pharmaceuticals, Bayer Corp., Portola Pharmaceuticals, Angel Medical Corporation, CSL Behring; has received grants from Bristol-Myers Squibb and SCAD Alliance; has received personal fees from The Medicines Company, Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly and Company, Gilead Sciences, Inc., Novo Nordisk, Web MD, UpToDate in Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck & Co., Inc., PharmaMar, Sanofi, Somahlution, St. Francis Hospital, Verreseon Corporation, Boston Scientific, Duke Clinical Research Institute, Impact Bio, Ltd., MedImmune, Medtelligence, Microport, PERT Consortium, GE Healthcare, Caladrius Bioscience, CeleCor Therapeutics, and Thrombolytic Science; has equity in nference; and has received nonfinancial support from Baim Institute. Dr. Mehran has received institutional research funding from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Sanofi, CSL Behring, Eli Lilly, Daiichi-Sankyo, Medtronic, Novartis, and OrbusNeich; has been a consultant to Boston Scientific, Abbott Vascular, Medscape, Web MD, PLxOpco Inc. (aka PLx Pharma Inc.), Siemens Medical Solutions, Regeneron Pharmaceuticals Inc., Roivant Sciences Inc., Sanofi, and Janssen Scientific Affairs; has been an institutional consultant with Abbott Vascular and Spectranetics/Phillips/Volcano Corporation; has served on the Executive Committees for Janssen Pharmaceuticals and Bristol-Myers Squibb; has received institutional funding for serving on the Scientific Advisory Boards of Bristol-Myers Squibb and Novartis; has received funding to institution for serving on the Data and Safety Monitoring Board of Watermark Research; has <1% equity with Claret Medical and Elixir Medical; and is an Associate Editor for the American College of Cardiology and the American Medical Association. Dr. Badimon has received grants from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Richard C. Becker, MD, served as Guest Editor for this paper.
- Received October 28, 2019.
- Accepted November 20, 2019.
- 2020 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.