Race and Socioeconomic Status Independently Affect Risk of Major Amputation in Peripheral Artery Disease

Background Rates of major lower extremity amputation in patients with peripheral artery disease are higher in rural communities with markers of low socioeconomic status, but most Americans live in metropolitan areas. Whether amputation rates vary within US metropolitan areas is unclear, as are characteristics of high amputation rate urban communities. Methods and Results We estimated rates of major lower extremity amputation per 100 000 Medicare beneficiaries between 2010 and 2018 at the ZIP code level among ZIP codes with ≥100 beneficiaries. We described demographic characteristics of high and low amputation ZIP codes, and the association between major amputation rate and 3 ZIP code–level markers of socioeconomic status—the proportion of patients with dual eligibility for Medicaid, median household income, and Distressed Communities Index score—for metropolitan, micropolitan, and rural ZIP code cohorts. Between 2010 and 2018, 188 995 Medicare fee‐for‐service patients living in 31 391 ZIP codes with ≥100 beneficiaries had a major lower extremity amputation. The median (interquartile range) ZIP code–level number of amputations per 100 000 beneficiaries was 262 (75–469). Though nonmetropolitan ZIP codes had higher rates of major amputation than metropolitan areas, 78.2% of patients undergoing major amputation lived in metropolitan areas. Compared with ZIP codes with lower amputation rates, top quartile amputation rate ZIP codes had a greater proportion of Black residents (4.4% versus 17.5%, P <0.001). In metropolitan areas, after adjusting for clinical comorbidities and demographics, every $10 000 lower median household income was associated with a 4.4% (95% CI, 3.9–4.8) higher amputation rate, and a 10‐point higher Distressed Communities Index score was associated with a 3.8% (95% CI, 3.4%–4.2%) higher amputation rate; there was no association between the proportion of patients eligible for Medicaid and amputation rate. These findings were comparable to the associations identified across all ZIP codes. Conclusions In metropolitan areas, where most individuals undergoing lower extremity amputation live, markers of lower socioeconomic status and Black race were associated with higher rates of major lower extremity amputation. Development of community‐based tools for peripheral artery disease diagnosis and management targeted to communities with high amputation rates in urban areas may help reduce inequities in peripheral artery disease outcomes.

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Stromal Cell–Derived Factor-1 Plasmid Treatment for Patients With Peripheral Artery Disease (STOP-PAD) Trial: Six-Month Results

Journal of Endovascular Therapy ◽

10.1177/1526602820919951 ◽

2020 ◽

Vol 27 (4) ◽

pp. 669-675

Author(s):

Tarek A. Hammad ◽

John Rundback ◽

Matthew Bunte ◽

Leslie Miller ◽

Parag D. Patel ◽

...

Keyword(s):

Wound Healing ◽

Peripheral Artery Disease ◽

Stromal Cell ◽

Biological Therapy ◽

Target Lesion ◽

Major Amputation ◽

Peripheral Artery ◽

Below The Knee ◽

Stromal Cell Derived Factor ◽

Artery Disease

Purpose: To present the 6-month results of the Stromal Cell–Derived Factor-1 Plasmid Treatment for Patients with Peripheral Artery Disease (STOP-PAD) trial. The trial was an attempt to alter the course of chronic limb-threatening ischemia (CLTI) with a biological agent vs placebo after successful arterial revascularization at or below the knee. Materials and Methods: The multicenter, randomized, double-blinded, placebo-controlled, phase 2B STOP-PAD trial ( ClinicalTrials.gov identifier NCT02544204) randomized 109 patients (mean age 71 years; 68 men) with Rutherford category 5 or 6 CLTI and evidence of persistent impaired forefoot perfusion following recent successful revascularization to 8- (n=34) or 16-mg (n=36) intramuscular injections of a non-viral DNA plasmid–based treatment vs placebo (n=34). The primary efficacy outcome was the 6-month wound healing score evaluated by an independent wound core laboratory; the primary safety endpoint was major adverse limb events (MALE), a composite of major amputation plus clinically-driven target lesion revascularization at 6 months. Results: Only one-third of the patients had complete wound healing at 6 months in the placebo (31%), 8-mg injection (33%), and 16-mg injection (33%) groups. In addition, the observed increase in the toe-brachial index from baseline to 6 months was statistically significant in each group; however, this did not result in lower rates of MALE at 6 months (24% in the placebo, 29% in the 8-mg injection, and 11% in the 16-mg injection groups). During the 6-month period, 6 patients (6%) died, and 24 patients (23%) had an amputation [only 4 (4%) major]. Conclusion: Combining revascularization and biological therapy failed to improve outcomes in CLTI at 6 months. STOP-PAD has provided insights for future trials to evaluate biological therapy.

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Socioeconomic Status and Incidence of Hospitalization With Lower‐Extremity Peripheral Artery Disease: Atherosclerosis Risk in Communities Study

Journal of the American Heart Association ◽

10.1161/jaha.116.004995 ◽

2017 ◽

Vol 6 (8) ◽

Cited By ~ 11

Author(s):

Priya Vart ◽

Josef Coresh ◽

Lucia Kwak ◽

Shoshana H. Ballew ◽

Gerardo Heiss ◽

...

Keyword(s):

Socioeconomic Status ◽

Lower Extremity ◽

Peripheral Artery Disease ◽

Peripheral Artery ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk ◽

Artery Disease ◽

Incidence Of Hospitalization

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Chronic kidney disease and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: The EUCLID trial

Vascular Medicine ◽

10.1177/1358863x19864172 ◽

2019 ◽

Vol 24 (5) ◽

pp. 422-430 ◽

Cited By ~ 1

Author(s):

Charles W Hopley ◽

Sarah Kavanagh ◽

Manesh R Patel ◽

Cara Ostrom ◽

Iris Baumgartner ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Ischemic Stroke ◽

Kidney Disease ◽

Peripheral Artery Disease ◽

Major Bleeding ◽

Cardiovascular Death ◽

Major Amputation ◽

Peripheral Artery ◽

Increased Risk ◽

Artery Disease

In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients with PAD to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. This post hoc analysis compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction (MI), or ischemic stroke) in patients with CKD (eGFR < 60 mL/min/1.73 m2) with those without CKD (eGFR ⩾ 60 mL/min/1.73 m2). The primary safety endpoint was thrombolysis in MI (TIMI) major bleeding. A total of 13,483 patients were included; 3332 (25%) had CKD, of whom 237 had stage 4/5 disease. Median follow-up was approximately 30 months. After statistical adjustment, patients with CKD had a higher rate of the primary endpoint compared with those without CKD (6.75 vs 3.72 events/100 patient-years; adjusted hazard ratio (HR) 1.45, 95% CI 1.30–1.63). CKD was not associated with increased risk of hospitalization for acute limb ischemia (ALI) (adjusted HR 0.96, 95% CI 0.69–1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66–1.28). CKD was not associated with a significantly increased risk of major bleeding (adjusted HR 1.21, 95% CI 0.89–1.64), but minor bleeding was significantly increased (adjusted HR 1.51, 95% CI 1.07–2.15). In conclusion, patients with PAD and CKD had higher rates of cardiovascular death, MI, and ischemic stroke, but similar rates of ALI, major amputation, and TIMI major bleeding when compared with patients without CKD. ClinicalTrials.gov Identifier: NCT01732822

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Vorapaxar for Prevention of Major Adverse Cardiovascular and Limb Events in Peripheral Artery Disease

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/10742484211056115 ◽

2022 ◽

Vol 27 ◽

pp. 107424842110561

Author(s):

Justin T. Morrison ◽

Nicholas Govsyeyev ◽

Connie N. Hess ◽

Marc P. Bonaca

Keyword(s):

Peripheral Artery Disease ◽

Limb Ischemia ◽

Major Amputation ◽

Acute Limb Ischemia ◽

Peripheral Artery ◽

Cellular Effects ◽

Thrombin Inhibition ◽

Severe Manifestation ◽

Artery Disease

Peripheral artery disease (PAD) is a severe manifestation of atherosclerosis. Patients with PAD are at heightened risk for atherothrombotic complications, including myocardial infarction and stroke (MACE); however, there is also an equal or greater risk of major adverse limb events (MALE), such as acute limb ischemia (ALI) and major amputation. Therefore, there is a need for effective medical therapies to reduce the risk of both MACE and MALE. Recent trials have demonstrated the role of thrombin inhibition in reducing the risk of MACE and MALE in PAD patients. One such medical therapy, vorapaxar, is a potent inhibitor of protease activated receptor-1 which mediates the cellular effects of thrombin. Vorapaxar, used in addition to aspirin, has demonstrated robust reductions in MACE and MALE in PAD patients. In this article, we provide a contemporary review of the current state of PAD and the role of antithrombotic medications in the treatment of PAD, as well as the current clinical data on vorapaxar and strategies to integrate vorapaxar into contemporary medical management of peripheral artery disease.

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Peripheral artery disease leading to major amputation: trends in revascularisation and mortality over 18 years

Annals of Vascular Surgery ◽

10.1016/j.avsg.2021.04.037 ◽

2021 ◽

Author(s):

Lisa Abry ◽

Salome Weiss ◽

Vladimir Makaloski ◽

Alan G. Haynes ◽

Jürg Schmidli ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Major Amputation ◽

Peripheral Artery ◽

Artery Disease

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Growth Differentiation Factor 15 Is Associated With Major Amputation and Mortality in Patients With Peripheral Artery Disease

Journal of the American Heart Association ◽

10.1161/jaha.117.006225 ◽

2017 ◽

Vol 6 (9) ◽

Cited By ~ 13

Author(s):

Judith J. De Haan ◽

Saskia Haitjema ◽

Hester M. den Ruijter ◽

Gerard Pasterkamp ◽

Gert J. de Borst ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Major Amputation ◽

Peripheral Artery ◽

Growth Differentiation Factor 15 ◽

Differentiation Factor ◽

Artery Disease

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SOCIOECONOMIC STATUS AND PERIPHERAL ARTERY DISEASE IN US ADULTS: NHANES 99-04

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(11)61563-5 ◽

2011 ◽

Vol 57 (14) ◽

pp. E1563

Author(s):

Reena L. Pande ◽

Todd S. Perlstein ◽

Joshua A. Beckman ◽

Mark A. Creager

Keyword(s):

Socioeconomic Status ◽

Peripheral Artery Disease ◽

Peripheral Artery ◽

Artery Disease

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Three-Year Outcomes From the LIBERTY 360 Study of Endovascular Interventions for Peripheral Artery Disease Stratified by Rutherford Category

Journal of Endovascular Therapy ◽

10.1177/1526602820962972 ◽

2020 ◽

pp. 152660282096297

Author(s):

Stefanos Giannopoulos ◽

Jihad Mustapha ◽

William A. Gray ◽

Gary Ansel ◽

George Adams ◽

...

Keyword(s):

Quality Of Life ◽

Peripheral Artery Disease ◽

Survival Rates ◽

Target Lesion ◽

Major Amputation ◽

Peripheral Artery ◽

Target Vessel Revascularization ◽

Endovascular Interventions ◽

Artery Disease

Purpose: To report the 3-year results of the LIBERTY 360 study, which investigated outcomes of endovascular treatment of symptomatic peripheral artery disease (PAD). Materials and Methods: The LIBERTY trial ( ClinicalTrials.gov identifier NCT01855412) was a prospective, observational, core laboratory–assessed, multicenter study of endovascular interventions enrolling >1200 participants treated at 51 sites. Data from 1189 patients were stratified according to Rutherford category (RC) and analyzed [RC 2-3 (n=500), RC 4-5 (n=589), and RC 6 (n=100)]. The primary outcomes were major amputation of the target limb and all-cause death; secondary outcomes were target vessel revascularization (TVR) or target lesion revascularization (TLR); major adverse events (MAEs; death within 30 days, TVR or TLR, and major amputation); death or major amputation combined; and change in self-reported quality of life (QoL) measures (VascuQol-25). The Kaplan-Meier (KM) method was employed to estimate the outcomes; estimates are presented with the 95% confidence intervals (CI). Predictors of 3-year MAE, death, TVR, and major amputation were analyzed using Cox proportional hazard regression modeling. Results: The 36-month KM survival rates were 86.0% in RC 2-3, 79.8% in RC 4-5, and 62.0% in RC 6 groups. The KM estimates of freedom from major amputation at 36 months were 98.5% in RC 2-3, 94.0% in RC 4-5, and 79.9% in RC 6. The 36-month KM estimates for freedom from TVR/TLR were 71.1% in RC 2-3, 64.2% in RC 4-5 and 61.9% in RC 6 groups. Patients with claudication at baseline were at lower risk for MAEs compared with RC 4-5 and RC 6 patients during the 36-month follow-up. Vascular QoL improved from baseline and persisted up to 36 months in all patients. Conclusion: Endovascular therapy is a viable treatment option for patients with symptomatic PAD, with sustained improved quality of life in both claudicants and patients with chronic limb-threatening ischemia. These results provide important point estimates for midterm outcomes after modern endovascular interventions for PAD.

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