WILLOW CCS - Version 1
Research type
Research Study
Full title
Characterisation of a novel regimen of very low-dose aspirin combined with rivaroxaban in patients with chronic coronary syndromes: WILL lOWer dose aspirin be better with rivaroxaban in patients with Chronic Coronary Syndromes? – (WILLOW CCS)
IRAS ID
273020
Contact name
Robert Storey
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Eudract number
2019-000267-25
Duration of Study in the UK
1 years, 3 months, 1 days
Research summary
Patients with Chronic Coronary Syndromes (CCS), including those with stable coronary artery disease or a history of heart attack >1 year ago at particular risk of major adverse cardiovascular events (MACE), including heart attack, may be treated with standard-dose aspirin (75 mg) once-daily. In high-risk individuals, adding low-dose twice-daily rivaroxaban, an anticoagulant, to standard treatment leads to a lower risk of MACE. This may be because the combination, known as dual antithrombotic therapy (DATT), provides both antiplatelet and anticoagulation effect, reducing the risk of blood clot formation. However this approach also leads to an increased risk of bleeding, dissuading clinicians and patients from long term use. Improving the safety of DATT could lead to wider applicability of the approach and improved clinical outcomes in patients at risk of MACE.
We previously showed a novel regimen of aspirin, 20 mg twice-daily, reduced peak effect of aspirin resulting in reduced bleeding risk when compared to standard-dose, in patients receiving a second antithrombotic drug. Trough steady-state effects were maintained with adequate antiplatelet effect over a 24-hour period. We also saw an expected reduction in inflammatory markers and no differences in clot formation parameters.
This study is comparing a twice-daily very-low-dose of aspirin plus rivaroxaban with two currently-used regimens: once-daily standard-dose aspirin alone, and once-daily standard-dose aspirin plus twice-daily rivaroxaban. Patients with a diagnosis of CCS, already taking aspirin 75 mg once-daily and meeting the study inclusion/exclusion criteria will be invited to participate. Patients will be randomised to one of two sequences, each containing three treatment periods, for a total of 36-42 days. Bleeding time measurements and blood/urine samples will be taken before and after the last dose of each treatment period.
Lay summary of study results: Patients with heart disease are often treated with 75 mg of aspirin once a day. A large study found that adding another blood-thinning drug, rivaroxaban, reduced the risk of future heart problems but also increased the chance of bleeding.
Our earlier research showed that taking aspirin at a lower dose but twice a day (20 mg twice a day) reduced bleeding risks while still providing effective protection against blood clotting round the clock.
The WILLOW CCS study was designed to see if combining this very-low-dose aspirin with rivaroxaban could improves markers of bleeding while still protecting against blood clots. The study tested three treatment options:
1. Aspirin 75 mg once a day
2. Aspirin 75 mg once a day combined with rivaroxaban
3. Aspirin 20 mg twice a day combined with rivaroxabanPatients received all three treatments in different orders. We measured bleeding time (marker of bleeding risk), blood clotting, and inflammation both before and after taking the medications to see how each treatment affected these factors.
The results showed that the combination of very-low-dose aspirin (20 mg twice a day) with rivaroxaban led to a shorter bleeding time compared to standard-dose aspirin (75 mg) with rivaroxaban. This combination also maintained good anti-clotting activity compared to the standard-dose treatments.
In summary, combining rivaroxaban with very-low-dose aspirin has less impact on bleeding while still effectively preventing blood clots, making it a promising approach to balance safety and effectiveness for patients at high risk of heart problems.REC name
London - City & East Research Ethics Committee
REC reference
20/LO/0147
Date of REC Opinion
21 Feb 2020
REC opinion
Favourable Opinion