November 16, 2020 — The use of the more potent antiplatelet medication ticagrelor (Brilinta) was not superior to clopidogrel in the reduction of heart attacks or severe complications among people undergoing an elective percutaneous coronary intervention (PCI), according to late-breaking research presented at the 2020 American Heart Association (AHA) Scientific Sessions. The manuscript of this study was simultaneously published in the Lancet.
The randomized, international, multi-center ALPHEUS trial enrolled 1,833 adults (average age 67% male ) at 49 centers in two European countries (France and the Czech Republic). The participants had heart disease and elected to undergo PCI to open a narrow or blocked blood vessel supplying blood to the heart.
The trial examined whether ticagrelor, a more potent antiplatelet medication than the standard of care (clopidogrel), may reduce the rate heart attack and complications around the time of the procedure for patients who are considered high-risk due to at least one additional underlying condition, such as renal insufficiency, diabetes, overweight, prior acute coronary syndome or heart failure, or because of a high risk procedure (multiple stents needed, bifurcation stenting, left main, etc.).
“While ticagrelor has been shown in previous studies to be beneficial in reducing blood clots among people who experienced a sudden blockage in a coronary artery, it has never been evaluated in patients undergoing elective percutaneous coronary intervention with more stable heart conditions,” said Johanne Silvain, M.D., Ph.D., lead study author, and an interventional cardiologist and director of the Coronary Intensive Care Unit at the Institut de Cardiologie of the Hospital Pitié-Salpêtrière in Paris.
The risk of severe complications, including stent clots, stroke and death, during percutaneous coronary intervention is less than 1% (the rate was 0.5% in the ALPHEUS trial). However, some patients experience heart attacks provoked by the PCI procedure itself.
In this study, a control group of patients received clopidogrel plus aspirin before PCI and for 30 days after the procedure. The experimental group received ticagrelor plus aspirin before PCI and for 30 days after.
The study, which was conducted over more than three years, found:
• The rate of periprocedural heart attack and severe complications, including stent clots, stroke and death, was similar between the control group and the experimental group.
• There was no increase in excessive bleeding 48-hours after PCI among the patients treated with ticagrelor compared to the control group.
“These results show there is no scientific data to support a change in the standard of care,” Silvain said. “The use of ticagrelor should be reserved for treating patients who experienced a sudden blockage in a coronary artery (acute coronary syndrome), not those who have stable heart conditions and elect PCI.”
Study limitations include that “it was an open label trial, myocardial infarction and injury were used as the clinical outcome as hard clinical endpoint, which are rare in elective PCI. Patients under chronic clopidogrel therapy were included, and all troponin assays were allowed to reflect real-life but may have brought heterogeneity,” he explained.
Co-authors are Benoit Lattuca, M.D., Ph.D.; Farzin Beygui, M.D., Ph.D.; Grégoire Range M.D.; Zuzana Motovska, M.D., Ph.D.; Jean-Guillaume Dillinger, M.D., Ph.D.; Ziad Boueri, M.D.; Philippe Brunel, M.D.; Thibault Lhermusier, M.D.; Christophe Pouillot, M.D.; Elisa Larrieu-Ardilouze, M.D.; Franck Boccara, M.D., Ph.D.; Jean-Noël Labeque, M.D.; Paul Guedeney, M.D.; Mohamad El Kasty, M.D.; Mikael Laredo, M.D.; Raphaëlle Dumaine, M.D.; Grégory Ducrocq, M.D., Ph.D.; Jean-Philippe Collet M.D.,Ph.D.; Guillaume Cayla, M.D., Ph.D.; Katrien Blanchart, M.D.; Petr Kala, M.D., Ph.D.; Eric Vicaut, M..D., Ph.D.; and Gilles Montalescot, M.D., Ph.D. Author disclosures are in the abstract.
Assistance Publique - Hôpitaux de Paris sponsored the study, which was led by the Action Group and funded by AstraZeneca.
1. Johanne Silvain, Benoit Lattuca, Farzin Beygui, et al. Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial. Lancet. Published online November 14, 2020. DOI:https://doi.org/10.1016/S0140-6736(20)32236-4.