Antiplatelet therapy following peripheral endovascular intervention

The effect of anti platelet therapy on amputation-free survival following lower limb peripheral endovascular intervention for patients with peripheral arterial disease.

Status

Completed

Phases

Unknown

Study type

Observational

Source

ANZCTR

Registry ID

ACTRN12618000523202

Enrollment

516

Registered

2018-04-10

Start date

2018-04-16

Completion date

2018-09-28

Last updated

2021-05-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Peripheral endovascular intervention describes a group of procedures which are used to open up arteries away from the heart which have been blocked by cardiovascular disease. The past decade has seen a huge expansion in these interventions, with cases increasing threefold in England over the past decade from around 12,000 cases in 2004-5 to over 33,000 in 2014-15 according to Hospital Episode Statistics. Despite this expansion, there is a dearth of high quality evidence regarding the optimal medical management of these patients. A high quality (Cochrane) review of anti-platelet and anticoagulant therapy in this context found only small trials which enrolled a mixture of patients with varying levels of disease, affecting a variety of peripheral arteries, in a mixture of diabetic and non-diabetic patients. Current practice is therefore varied, with some practitioners borrowing evidence from cardiology trials. Doing so is attractive, as multiple large randomised controlled trials of coronary endovascular interventions have enrolled thousands of patients. Good evidence supports the use of dual anti-platelet therapy with aspirin and a thienopyridine derived agent such as clopidogrel in this setting. However there are key differences between coronary and peripheral arterial intervention. In coronary disease the majority of trial evidence relates to sudden vessel blockages (acute vessel thrombosis) leading to myocardial infarction. By contrast, peripheral intervention is principally performed in patients with stable disease. Results of a large trial have resulted in a move towards routine stent implantation (placing a permanent metal tube within the artery in an attempt to keep it open) in coronary intervention, whereas the evidence for lower limb endovascular procedures has led the UK National Institute for Health and Care Excellence to recommend angioplasty (using a balloon to open up an artery) without stenting. Our hypothesis, which is borne out by the limited amount of research that currently exists in this area, is that dual anti-platelet therapy following peripheral endovascular intervention has significant benefits in terms of both increasing the likelihood that arteries which have been re-opened by angioplasty will remain open (lesion patency), and also reducing the chances that the patient will suffer other cardiovascular events in the early post-procedural period. We will perform a review of patients treated with peripheral endovascular intervention in our region since 2010 to assess the effect of different anti-platelet medications on outcomes. The primary outcome will be amputation free survival. Secondary outcomes will be limb salvage, overall survival and the need for further intervention.

Interventions

Patients undergoing peripheral endovascular intervention (angioplasty and/or stenting of the iliac, femoral, popliteal, tibial or peroneal arteries) for treatment of peripheral arterial disease at Aneurin Bevan University Health Board between January 2010 and January 2017 and not receiving therapeutic anticoagulation following the procedure. Patients will be followed up for a minimum of 12 months following their procedure for assessment of outcomes. Exposure arm is according to the antiplatelet agents documented in the medical notes as being given following the procedure. Arm 1: Neither Aspirin at a dose of at least 75mg daily, nor any P2Y12 inhibitor (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose) given orally following peripheral endovascular intervention. Arm 2: Aspirin at a dose of at least 75mg daily given orally following peripheral endovascular intervention without concomitant P2Y12 inhibitor (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose). Arm 3: P2Y12 inhibitor given orally following peripheral endovascular intervention (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose) without concomitant oral aspirin at a dose of 75mg daily or more. Arm 4: Aspirin at a dose of at least 75mg daily given orally AND a P2Y12 inhibitor given orally following peripheral endovascular intervention (this is likely to be clopidogrel 75mg daily in the majority of cases, but could be ticlopidine, prasugrel, ticagrelor, or any other P2Y12 inhibitor at a standard therapeutic dose). Patients receiving antiplatelet agents other than aspirin or a P2Y12 inhibitor will be included and their treatment arm determined according to the rules above. Treatment administered is at the discretion of the treating clinician - all treatments are routinely administered as part of standard care and documented in the medical notes. Treatment arm will be allocated based on the treatment given immediately following the procedure, not the duration of treatment.

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

• Patients undergoing primary angioplasty or stenting with bare metal or drug-eluting stents of the infra-renal aorta; common or external iliac arteries; common, superficial or deep femoral artery; popliteal artery; tibio-peroneal trunk; anterior or posterior tibial artery or peroneal artery or any pedal artery for stenotic or occlusive peripheral arterial disease • Patients undergoing primary angioplasty or stenting of a stenosis in a surgical bypass graft running between two of the included arteries mentioned above • Patients already included in the study by virtue of treatment of the contralateral limb, who subsequently undergo endovascular therapy to the other leg

Exclusion criteria

• Patients undergoing treatment for aneurysmal disease, or for a complication of treatment of aneurysmal disease • Lesions treated with covered stent grafts • Patients already recruited into the study and undergoing repeated endovascular therapy to the same limb • Patients undergoing treatment proximal to the infra-renal aorta, to the upper limb, head and next vessels, mesenteric or renal vessels • Patients undergoing diagnostic angiogram only, with no attempt made to perform angioplasty • Patients undergoing intra-arterial embolectomy, thrombectomy or thrombolysis, other than those where this is commenced immediately following primary angioplasty or stenting in order to treat a complication. • Venous procedures (e.g. stenting of veins following DVT) • Angioplasty or stenting of arterio-venous fistulas • Treatment of arterio-venous malformations • Patients receiving therapeutic anticoagulation in the form of therapeutic dose low molecular weight heparin; or warfarin with a target international normalised ratio of 2.0 or more; or a direct oral anticoagulant such as apixaban, dabigatran or rivaroxaban at therapeutic dosage.

Outcome results