GEMINI-ACS-1 Study Evaluates Safety of Rivaroxaban in Post-ACS Patients
March 18, 2017—The American College of Cardiology (ACC) announced that findings from the GEMINI-ACS-1 study demonstrated that patients with acute coronary syndrome (ACS) who were treated with the oral anticoagulant rivaroxaban in addition to an antiplatelet medication (clopidogrel or ticagrelor) experienced no increase in bleeding complications compared with patients who received the standard treatment of aspirin plus an antiplatelet drug.
E. Magnus Ohman, MD, Lead Investigator of GEMINI-ACS-1, presented the findings at ACC's 66th annual scientific session in Washington, DC. The study was simultaneously published online by Dr. Ohman et al in The Lancet.
In the ACC announcement, Dr. Ohman commented, “The current standard of care for ACS is for patients to take lifelong aspirin, even though there is little evidence that this is effective in preventing a recurrent heart attack after the early phase in ACS. This study is important because it is the first to show that replacing aspirin with a newer, more targeted drug—low-dose rivaroxaban, an anticoagulant—presents no additional risk of bleeding complications when given as dual therapy with an antiplatelet drug.” Dr. Ohman is Professor of Medicine at Duke University Medical Center in Durham, North Carolina.
The announcement explained the background of the study, which is that current ACC and American Heart Association guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus clopidogrel or a similar drug such as ticagrelor after a heart attack. However, other studies show that even when patients receive optimal DAPT, approximately 10% will experience an adverse event such as a heart attack or stroke. Earlier trials exploring the effect of adding an anticoagulant agent such as rivaroxaban to DAPT showed that this three-drug approach increased the risk of bleeding complications twofold or more.
Dr. Ohman reported that in the GEMINI-ACS-1 study, clinically significant bleeding—the study’s primary endpoint—occurred equally, in 5.3% of patients who received rivaroxaban compared with 4.9% of those who received aspirin, not a statistically significant difference. The most common type of bleeding was minor bleeding, such as a nosebleed for which the patient needed to see a doctor. Bleeding rates did not significantly differ between patients on clopidogrel and those on ticagrelor.
As summarized in the ACC press release, GEMINI-ACS-1 enrolled 3,037 patients in 21 countries (average age, 63 years; 75% men). Patients were enrolled in the study within 10 days of being hospitalized with a heart attack (89%) or unstable angina (11%). Patients were excluded if they had a history of impaired kidney function, active bleeding, or bleeding in the brain or gastrointestinal tract within the previous year. Patients receiving long-term anticoagulant therapy were also excluded.
After patients had been on a stable dose of clopidogrel or ticagrelor for more than 48 hours, they were randomly assigned to receive either low-dose rivaroxaban (2.5 mg twice per day) or aspirin (100 mg per day). The study was double blinded.
Patients were treated for a median of 291 days; the median follow-up period was 326 days. The number of patients who discontinued the study treatment prematurely was similar in the rivaroxaban and aspirin groups (11.3% vs 12.7%).
The investigators also evaluated the rate of death caused by a heart attack, stroke, other heart or vascular disease, or a blood clot in a coronary artery in which a stent had been placed. The rate was 5% for rivaroxaban and 4.7% for aspirin, not a statistically significant difference.
Although the findings of this phase 2 trial show that treatment with rivaroxaban and an antiplatelet drug is safe, they do not demonstrate that this drug regimen is effective in preventing recurrent heart attacks. A larger phase 3 trial would be required to definitively establish that this treatment approach is both safe and effective. Another limitation is that because 93% of those participating in the study were Caucasian, the findings may not apply to more racially and ethnically diverse groups of patients, advised Dr. Ohman in the ACC press release.
The study was funded by a grant to Duke University and Harvard School of Medicine by Janssen Research & Development and Bayer AG.