CLARITY

CLopidogrel, Aspirin and RIvaroxaban after revascularisation with angioplasTY.

Background

Blocked leg arteries are very common and are often caused by diabetes or smoking. Blocked leg arteries are becoming more common as diabetes becomes more common and can lead to amputation, or even death if left untreated. Each year in the United Kingdom (UK), between 16,500 and 30,000 people die and 3,500 legs are amputated because of heavily blocked leg arteries. The most common way to reduce these risks is to open the blocked arteries with a balloon or stent, a procedure called an angioplasty.

Over 4,000 angioplasties to increase blood flow in the leg are performed each year in the UK. Patients are given blood-thinning tablets after the procedure to reduce the risk of artery-blocking again, amputation, and blockages of other arteries in the body therefore preventing heart attack, stroke or death.

There are many types of blood-thinning tablets, and no one knows which one or combination is the best. Sometimes, two types are used together. If two blood thinners work better than one, we may be able to save up to 1,600 lives and prevent 800 amputations each year in the UK by using them routinely.

Study Design

The study will compare three different combinations of blood-thinning tablets after angioplasty. The study will be a ‘randomised’ trial. This means patients will be randomly chosen to have either:

1. Clopidogrel
2. Aspirin and Clopidogrel
3. Aspirin and Rivaroxaban

Participants will take the tablets for up to three years. We will follow them up to see if a certain tablet or combination of tablets is better at saving legs and lives after angioplasty. We will also check that the tablets do not cause too much bleeding.

Patient and public involvement

The selection of drugs we are using was collaboratively chosen with input from PPI and UK-based clinician using questionnaires and group discussions in 2019 and 2022.

We had two members of the public on the trial development group. One takes blood-thinning tablets for blocked leg arteries and one has parents who died of blocked leg arteries. Ten people who had taken blood thinners confirmed their acceptance of being involved in a trial of blood thinners to prevent amputation. Subsequently, six people who had taken blood thinners helped develop the trial and what it would measure. For example, they had a clear preference for preventing amputation resulting from blocked arteries and their feedback reduced the number of questionnaires.

Publications

• Twine CP, Ahmed H, Lugg-Widger FV, Waldron CA, Bown MJ, Sydes MR. Challenges of Using Routinely Collected Healthcare System Data in Randomised Trials. Eur J Vasc Endovasc Surg. 2024 May 10:S1078-5884(24)00388-5. doi: 10.1016/j.ejvs.2024.05.010. Epub ahead of print.

Publication: https://www.ejves.com/article/S1078-5884(24)00388-5/abstract

• Twine CP, Kakkos SK, Aboyans V, Baumgartner I, Behrendt CA, Bellmunt-Montoya S, et al. Editor’s Choice - European Society for Vascular Surgery (ESVS) 2023 Clinical  Practice Guidelines on Antithrombotic Therapy for Vascular Diseases. Eur J Vasc Endovasc Surg. 2023 May;65(5):627–89.

Open access: https://www.ejves.com/article/S1078-5884(23)00284-8/fulltext

• Ambler GK, Waldron CA, Contractor UB, Hinchliffe RJ, Twine CP. Umbrella review and meta-analysis of antiplatelet therapy for peripheral artery disease. Br J Surg. 2020 Jan;107(1):20–32.

Open access: https://academic.oup.com/bjs/article/107/1/20/6120942

• Chinai N, Ambler GK, Wardle BG, Locker D, Bosanquet D, Goyal N, et al. Single versus dual antiplatelet therapy following peripheral arterial endovascular intervention for chronic limb threatening ischaemia: Retrospective cohort study. PLoS One. 2020;15:e0234271.

Open access: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234271

• Qureshi MI, Li HL, Ambler GK, Wong KHF, Dawson S, Chaplin K, et al. Antiplatelet and Anticoagulant Use in Randomised Trials of Patients Undergoing Endovascular Intervention for Peripheral Arterial Disease: Systematic Review and Narrative Synthesis. Eur J Vasc Endovasc Surg. 2020;60:77-87.

Open access: https://www.ejves.com/article/S1078-5884(20)30238-0/fulltext

• Wong KHF, Bosanquet DC, Ambler GK, Qureshi MI, Hinchliffe RJ, Twine CP. The CLEAR (Considering Leading Experts’ Antithrombotic Regimes around peripheral  angioplasty) survey: an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention. CVIR Endovasc. 2019 Nov;2(1):37.

Open access: https://cvirendovasc.springeropen.com/articles/10.1186/s42155-019-0079-8