Amputation Risks Higher After Revascularization in Younger vs Older PAD Patients

Following an emergency lower limb revascularization, people with PAD who are in their 50s have a higher risk than those in their 80s of needing major amputation, according to a large analysis of patients in England.

The researchers say the poor limb salvage rates they found in younger PAD patients, coupled with poor outcomes in general for those needing nonelective treatment, highlight the need for better planning.

“It is therefore of vital importance to involve interventions early, such as early diagnosis, lifestyle risk factors adjustment, and having treatment care planned in advance to help prevent patients [from developing] the late-stage severe forms of PAD,” lead study author Qiuju Li, PhD (London School of Hygiene and Tropical Medicine, England), told TCTMD.

Among patients in their 50s who had emergency revascularization, the risk of major amputation at 1 year and 5 years was 18% and 28.8%, respectively. By contrast, those in their 80s had an 11.9% risk at 1 year that increased to 17% at 5 years. Patients in the older age group were overall at higher risk of death after revascularization, with or without the contribution of major amputation, than younger patients regardless of whether revascularization was emergent or elective, however.

The study was published July 22, 2024, in Circulation.

In an email, Li said the study represents the distribution of PAD patients with different types of revascularization procedures in the real world. Its source is the nationwide Data from Hospital Episode Statistics Admitted Patient Care, an administrative database that collects information on all admissions to hospitals within the National Health Service (NHS) in England.

Commenting for TCTMD, Sahil Parikh, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), said that while the study is hypothesis generating, it includes a mixture of different patient types treated only within the NHS, where it has been shown that PAD is often identified late in the disease course. This, he noted, makes it difficult to generalize the findings to the PAD population at large.

“We know that age is a powerful risk factor, but if you're identified with PAD at a younger age it probably marks a higher, more aggressive form of the disease,” he said. “I know the authors tried to correct for that, but it's difficult to do in these analyses.”

Still, Parikh said the study is yet another reminder of the need to optimize the management of younger patients so they don’t get to the point of needing emergency revascularization.

“Once the diagnosis is made, the treatment has to be incredibly aggressive both medically and, when needed, with revascularization,” he said. “We’d assume from this study that these patients were diagnosed and in the system receiving appropriate treatment, but given the realities of wait times it’s hard to know if people had delays or barriers to getting appointments and that’s why they presented young and in an emergency situation.”

Illness-Death Model

To explore how patient and clinical disease characteristics influenced death and major amputation after lower limb revascularization, Li and colleagues employed an illness-death model, also known as a Markov multistate model. Between April 2013 and March 2020, 94,690 PAD patients (median age 72 years; 34% women) underwent emergent (34.8%) or elective (65.2%) revascularization in NHS hospitals. Procedure type was endovascular in 74%, open surgery in 20%, and hybrid revascularization in the remaining patients.

Approximately 40% of the cohort had diabetes, more than half had one or more Charlson comorbidity, and nearly 40% were categorized as severely frail. Compared with elective procedures, patients who had emergency revascularizations were older and more likely to have diabetes, tissue loss, and moderate or severe frailty.

At a median follow-up of 4.9 years, 10% of the cohort had a major amputation. Among them, 66.8% had undergone an emergency revascularization.

The cumulative risk of major amputation at 5 years was 10.8% in patients 50 to 54 years of age and 6.5% in those 80 to 84 years of age. In the older age group, the rate of death after major amputation was 39.2% if the amputation occurred within 3 months of revascularization and 29.8% if it occurred within 1 year. In the younger patient population, the death rates were 20.3% and 14.9%, respectively.

Compared with the older age group, the percentage contribution of major amputation to mortality was higher in the younger age group, but only when the procedure was nonelective.

Once the diagnosis is made, the treatment has to be incredibly aggressive both medically and, when needed, with revascularization. Sahil Parikh

Among the study’s limitations are that repeat revascularizations after the index procedure, which might indicate a more severe disease state, were not included in the model. Additionally, the severity of PAD was not classified using a standard scale, with the classification based on presentation and tissue loss only. It also is not discernable from the data how many of the patients had acute limb ischemia at presentation and no information was available on medication use or smoking status.

Asked whether the vast majority of patients having undergone endovascular procedures skews the generalizability of the results to all PAD revascularizations, Li said there might be some differences in exact risks of outcomes between patient groups undergoing different types of procedures.

As for the illness-death model, the researchers say it has potential to be used more widely in cardiology.

“Multistate models can be used to capture a complete picture of disease progression, and therefore provide a much more comprehensive understanding of disease trajectories,” Li noted.

Parikh said artificial intelligence may be an option to help train the model to be more effective and more reflective of real-world populations.

“It does seem like it could have a lot of possibilities,” he said. “The question is how predictive is it in a global population. You would want it to be scalable to extend to other populations, both in continental Europe and the US, and maybe then to a lesser degree to the other geographies where the genetic identity of the patients is going to be largely different.”