New guidance aims to improve blood clot prevention in chronic limb-threatening ischemia patients

A new statement from leading heart and blood vessel experts in Europe is providing clinical guidance for treatments to prevent blood clots in patients with a serious condition called chronic limb-threatening ischemia (CLTI), after they have had procedures to restore blood flow in their lower limbs. The statement, and the systematic review it is based on, comes from the European Society of Cardiology (ESC) Working Group on Aorta and Peripheral Vascular Diseases and Working Group on Cardiovascular Pharmacotherapy.

Prof. Christian Heiss, Professor of Cardiovascular Medicine at the University of Surrey and interventional NHS consultant, is an author of this comprehensive review, published in the European Heart Journal. It is the first such statement to specifically address this group of vulnerable patients. It points out a lack of dedicated research and states that using dual pathway inhibition (DPI) and dual antiplatelet therapy (DAPT) after procedures improves outcomes in CLTI patients.

CLTI is a severe form of peripheral artery disease (PAD), where blood flow to the legs and feet is severely reduced. It is characterised by severe leg pain that occurs even when resting, due to a lack of oxygen in the muscles, and wounds or ulcers on the feet or legs that are unable to heal because of poor blood circulation.

Patients with CLTI often need lower limb revascularization (LLR), which are procedures to restore blood flow. These can be less invasive, like angioplasty (using a balloon to open a narrowed artery) or stenting (placing a small mesh tube to keep the artery open); more invasive procedures, like bypass surgery, create new paths for blood to flow around blocked arteries.

However, even after these procedures CLTI patients may face a high risk of serious complications including Major Adverse Limb Events (MALE) - problems related to the affected leg, including further procedures on the limb, major amputation, or death from a limb-related issue; and Major Adverse Cardiovascular Events (MACE) - serious heart-related issues, such as heart attack, stroke, or death from a cardiovascular cause.

An international team including University of Surrey researchers based their statement on 34 scientific articles and found that while only three large-scale randomised controlled trials (RCTs) directly researched treatments to prevent blood clots in CLTI patients after LLR, none clearly showed a superior outcome.

However, promising clues emerged from broader studies: eight RCTs that looked at blood clot prevention in general PAD populations (which included some CLTI patients) suggested that Dual Antiplatelet Therapy (DAPT) might be beneficial in preventing limb-related issues. DAPT typically involves taking two different antiplatelet medications, most commonly, aspirin and clopidogel, which help stop blood cells called platelets from clumping together to form clots. Furthermore, data from 22 observational studies indicated that DAPT was linked to a lower risk of MALE, as well as improved overall survival and the chances of avoiding an amputation.

Significantly, one RCT showed that Dual Pathway Inhibition (DPI), which combines aspirin with a low dose of blood thinner rivaroxaban, significantly reduced the risk of MALE, MACE, and the need for further procedures on the treated limb. This makes DPI the only treatment supported by a large, high-quality study that has been shown to reduce both major limb-related and heart-related complications after LLR.

Professor Christian Heiss, the upcoming chairperson of the expert group, coauthor of the ESC statement, NHS consultant and Professor of Cardiovascular Medicine at the University of Surrey, said:

"This review highlights a need for more dedicated, large-scale research specifically focused on blood clot prevention therapies for patients with CLTI after their revascularisation procedures.

"While current guidelines offer general advice for peripheral artery disease, the unique vulnerability of CLTI patients, including their susceptibility to bleeding complications, demands tailored approaches to improve their outcomes and prevent negative consequences.

"Additionally, a direct comparison of DPI versus DAPT in CLTI patients after LLR is needed to determine the best approach."