scholarly journals Incidence and Factors Associated With Major Amputation in Patients With Peripheral Artery Disease

2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Chandler A. Long ◽  
Hillary Mulder ◽  
F. Gerry R. Fowkes ◽  
Iris Baumgartner ◽  
Jeffrey S. Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Mortality Rate ◽  
Peripheral Artery Disease ◽  
Limb Ischemia ◽  
Major Amputation ◽  
Peripheral Artery ◽  
Factors Associated ◽  
Increased Risk ◽  
Baseline Group ◽  
Artery Disease

Background: Peripheral artery disease (PAD) is associated with increased risk of mortality, cardiovascular morbidity, and major amputation. Data on major amputation from a large randomized trial that included a substantial cohort of patients without critical limb ischemia (CLI) have not been described. The objective was to describe the incidence and types of amputations in the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease) population, subcategorize amputations in the CLI versus no CLI cohorts, and describe the events surrounding major amputation. Methods and Results: Postrandomization major amputation was analyzed in the EUCLID trial. Patients were stratified by baseline CLI status. The occurrence of major amputation was ascertained and defined as the highest level. Perioperative events surrounding major amputation were obtained including acute limb ischemia, revascularization, and all-cause mortality. All variables were assessed for significance in univariable and multivariable models. The rate of major amputation during the course of the trial was 1.6% overall, 8.4% in the CLI at baseline group, and 1.2% in the no CLI at baseline group. The annualized rate of major amputation was 0.6% in PAD overall, 3.9% in the CLI at baseline group, and 0.5% in the no CLI at baseline group. Several factors were associated with increased risk of major amputation, including history of amputation, the presence of diabetes mellitus, baseline Rutherford category 4 to 6, and an ankle-brachial index <0.8. Factors associated with a lower risk for major amputation included prior statin use. The 30-day mortality rate after major amputation was 6.5% overall, 5.6% in the CLI at baseline group, and 6.8% in the no CLI at baseline group. The annual mortality rate following major amputation was 22.8% in the CLI at baseline group and 16.0% in the no CLI at baseline group. Conclusions: The risk factors for major amputation in EUCLID patients are similar to previous large registries’ reports except for diabetes mellitus in patients with CLI. The mortality following major amputation is lower in the EUCLID trial compared with registry data. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

scholarly journals Major Limb Outcomes Following Lower Extremity Endovascular Revascularization in Patients With and Without Diabetes Mellitus

2017 ◽  
Vol 24 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Andrew N. Shammas ◽  
Haekyung Jeon-Slaughter ◽  
Shirling Tsai ◽  
Houman Khalili ◽  
Mujtaba Ali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Endovascular Procedures ◽  
Major Amputation ◽  
Peripheral Artery ◽  
Entire Study ◽  
Endovascular Revascularization ◽  
Increased Risk ◽  
Artery Disease

Purpose: To determine whether diabetes mellitus has an independent impact on major limb outcomes at 1 year after endovascular treatment of lower extremity peripheral artery disease (PAD). Methods: The study involved 1906 consecutive patients (mean age 66 years; 1469 men) enrolled in the observational Excellence in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier NCT01904851) between January 2005 and October 2015 after undergoing index endovascular procedures in 2426 limbs for arterial occlusive disease. Patient outcomes included 12-month target limb amputation (above ankle) and target limb revascularization as well as all-cause death. Kaplan-Meier analysis and adjusted Cox proportional hazard models were used for time-to-event analysis of outcomes for the entire study sample as well as for the critical limb ischemia (CLI) and claudication subgroups. Results of the Cox regression models are reported as the hazard ratio (HR) and 95% confidence interval (CI). Results: Diabetics undergoing endovascular procedures had higher rates of comorbid conditions (p<0.001), CLI (p<0.001), heavily calcified lesions (p=0.002), multivessel disease (p=0.030), and fewer infrapopliteal runoff vessels (p<0.001). Regression analysis after adjusting for confounders revealed significantly higher target limb major amputation in diabetics compared with nondiabetics (HR 5.02, 95% CI 1.44 to 17.56, p=0.011). However, repeat revascularization rates were similar. When considering CLI and claudication subgroups, diabetes was associated with a nonsignificant increased risk of 12-month major amputation only for patients presenting with CLI (HR 3.48, 95% CI 0.97 to 12.51, p=0.056). Diabetes was also associated with an increased risk of 12-month all-cause mortality in the overall study sample (HR 4.64, 95% CI 2.01 to 10.70, p<0.001) and in the CLI subgroup (HR 14.15, 95% CI 3.16 to 63.32, p<0.001) but not in the claudication subgroup (HR 1.42, 95% CI 0.45 to 4.54, p=0.552). Conclusion: Diabetes increases the risk of major amputation and all-cause death at 12 months following endovascular revascularization in patients with symptomatic PAD. These risks are especially heightened in patients presenting with CLI.

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

2019 ◽  
Vol 24 (5) ◽  
pp. 422-430 ◽  
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

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

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.

Abstract 18307: Prevalence, Predictors and Prognostic Impact of High On-treatment Platelet Reactivity to Aspirin and Clopidogrel in Patients With Symptomatic Peripheral Artery Disease in Japanese Population

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
KEIKO FUKINO ◽  
Koji Hozawa ◽  
Takahiro Matsumoto ◽  
Hisaaki Ishiguro ◽  
Sunao Nakamura
Keyword(s):  
Peripheral Artery Disease ◽  
Japanese Population ◽  
Platelet Reactivity ◽  
Asian Population ◽  
Limb Ischemia ◽  
Tissue Loss ◽  
Prognostic Impact ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Introduction: High on-treatment platelet reactivity (HPR) is associated with increased risk of ischemic events and therapeutic failure in patients with coronary artery disease, whereas its role in patients with peripheral artery disease is not widely reported. Purpose: This study aims to investigate the prevalence of HPR in patients with symptomatic peripheral artery disease and its possible predictors in Asian population. Methods: Among patients who underwent endovascular therapy at our institution during September 2013 to April 2014, 125 patients who received aspirin and/or clopidogrel were included. Residual platelet reactivity was assessed with VerifyNow aspirin and P2Y12 assays. HPR was defined as aspirin reaction units (ARU) ≧ 550 for aspirin and P2Y12 reaction units (PRU) ≧ 235 for clopidogrel. Results: The prevalence of HPR to aspirin was not significantly different between patients with intermittent claudication (IMC) and critical limb ischemia patients (22.2% and 23.2%, respectively), whereas the prevalence of HPR to clopidogrel was higher in CLI patients, especially in patients with tissue loss compared to IMC patients (39.3% and 62.5%, respectively, p<0.05). 7.7% of IMC patients and 12.5% of CLI patients showed HPR to both aspirin and clopidogrel. Multivariate analysis revealed that age and diabetes were independent predictors for HPR to clopidogrel. Conclusion: HPR to aspirin and/or clopidogrel was highly prevalent in symptomatic PAD patients in Japanese population. The prevalence of HPR was significantly higher in patients with tissue loss compared with those without. Optimizing antiplatelet regimen according to residual platelet reactivity in CLI patients would be indispensable to avoid repeat revascularization and unexpected amputation.

scholarly journals Noncoding RNAs in Critical Limb Ischemia

2020 ◽  
Vol 40 (3) ◽  
pp. 523-533 ◽  
Author(s):  
Daniel Pérez-Cremades ◽  
Henry S. Cheng ◽  
Mark W. Feinberg
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Peripheral Artery Disease ◽  
Critical Limb Ischemia ◽  
Noncoding Rnas ◽  
Arterial Occlusion ◽  
Limb Ischemia ◽  
Limb Amputation ◽  
Peripheral Artery ◽  
Artery Disease

Peripheral artery disease, caused by chronic arterial occlusion of the lower extremities, affects over 200 million people worldwide. Peripheral artery disease can progress into critical limb ischemia (CLI), its more severe manifestation, which is associated with higher risk of limb amputation and cardiovascular death. Aiming to improve tissue perfusion, therapeutic angiogenesis held promise to improve ischemic limbs using delivery of growth factors but has not successfully translated into benefits for patients. Moreover, accumulating studies suggest that impaired downstream signaling of these growth factors (or angiogenic resistance) may significantly contribute to CLI, particularly under harsh environments, such as diabetes mellitus. Noncoding RNAs are essential regulators of gene expression that control a range of pathophysiologies relevant to CLI, including angiogenesis/arteriogenesis, hypoxia, inflammation, stem/progenitor cells, and diabetes mellitus. In this review, we summarize the role of noncoding RNAs, including microRNAs and long noncoding RNAs, as functional mediators or biomarkers in the pathophysiology of CLI. A better understanding of these ncRNAs in CLI may provide opportunities for new targets in the prevention, diagnosis, and therapeutic management of this disabling disease state.

P935Effect of hypertension and systolic blood pressure on cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: the EUCLID trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W Hiatt ◽  
C W Hopley ◽  
S Kavanagh ◽  
M R Patel ◽  
I Baumgartner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Peripheral Artery Disease ◽  
Limb Ischemia ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Cardiac Events ◽  
Increased Risk ◽  
History Of ◽  
Artery Disease

Abstract Background Hypertension is a risk factor for major adverse cardiac events (MACE) in patients with symptomatic peripheral artery disease (PAD). Purpose The effects of a history of hypertension and baseline systolic blood pressure (SBP) on MACE and major adverse limb events (MALE), including acute limb ischemia and major amputation, were evaluated in the Examining Use of tiCagreLor In paD (EUCLID) trial. Methods EUCLID randomized 13,885 patients with PAD and found no benefit of ticagrelor compared with clopidogrel on risk of MACE or MALE. The median duration of follow up was approximately 30 months. This post hoc, subgroup analysis evaluated the effects of hypertension history at baseline on the hazard for MACE and MALE. An adjusted restricted cubic spline regression analysis evaluated the association of SBP with MACE and MALE. Results A clinical history of hypertension was present in 10,857 (78%) patients at baseline and these patients were more likely to be older, female, white or African American, and reside in North America compared with the 3026 without hypertension. Hypertension was associated with a higher prevalence of concomitant cardiovascular diseases, polyvascular disease, diabetes, and prior coronary interventions. MACE occurred at a rate of 4.63 events/100 pt-yrs in participants with hypertension and 3.64 events/100 pt-yrs in participants without hypertension, (adjusted hazard ratio [aHR] 0.94, 95% CI 0.82–1.08; p=0.38). MALE occurred at a rate of 1.11 events/100 pt-yrs in those with hypertension and 1.38 events/100 pt-yrs in those without hypertension (p=0.054) (aHR 0.93 (95% CI 0.73, 1.18) p=0.55. The adjusted spline model for MACE and SBP demonstrated a significantly non-linear relationship with a HR 1.08 (95% CI 1.01, 1.15), p=0.0275 for every 10-unit decrease <135 mmHg SBP and HR 1.11 (1.06, 1.16), p<0.0001 for every 10-unit increase >135 mmHg (figure). There was no association between baseline SBP and MALE events. Conclusions A history of hypertension was not associated with a higher adjusted hazard for MACE or MALE in participants with PAD. In contrast, SBP at baseline was associated with increased risk of MACE at values both above and below 135 mmHg. Acknowledgement/Funding EUCLID was sponsored by AstraZeneca

scholarly journals Reduction in Acute Limb Ischemia with Rivaroxaban versus Placebo in Peripheral Artery Disease after Lower Extremity Revascularization: Insights from VOYAGER PAD

Circulation ◽  
2021 ◽  
Author(s):  
Connie N. Hess ◽  
E. Sebastian Debus ◽  
Mark R. Nehler ◽  
Sonia S. Anand ◽  
Manesh R. Patel ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Cumulative Incidence ◽  
Low Dose ◽  
Limb Ischemia ◽  
Major Amputation ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Prior lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. Methods: VOYAGER PAD (NCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan Meier estimates, and Cox proportional-hazards models were used to generate hazard ratios and associated confidence intervals. Analyses were performed as intention-to-treat. Results: Among 6,564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, prior LER, baseline ABI <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (HR 2.59, 95% CI 1.98-3.39) and major amputation (HR 24.87, 95% CI 18.68-33.12). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction 2.6% at 3 years, HR 0.67, 95% CI 0.55-0.82, P=0.0001), with benefit starting early (HR 0.45, 95% CI 0.24-0.85, P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and ICU stay, HR 0.58, 95% CI 0.40-0.83, P=0.003) and regardless of LER type (surgical vs endovascular revascularization, p-interaction=0.42) or clopidogrel use (p-interaction=0.59). Conclusions: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Under-Prescription of Medical Treatment for Peripheral Artery Disease in the Under 50s: A Retrospective Study

Angiology ◽  
2021 ◽  
pp. 000331972110421
Author(s):  
Simon Soudet ◽  
Lorène Bultel ◽  
Lamrani Adnane ◽  
Thierry Reix ◽  
Marie Antoinette Sevestre
Keyword(s):  
Medical Treatment ◽  
Peripheral Artery Disease ◽  
Young Patients ◽  
Limb Ischemia ◽  
Major Amputation ◽  
University Hospital ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Artery Disease

Peripheral artery disease (PAD) is a common cause of morbidity and mortality; however, data on its etiology and evolution in patients under 50 years old are scarce. Therefore, we performed a retrospective analysis of data from medical records, including cardiovascular risk factors, etiology, medical and surgical treatment, and follow-up. We included all patients with PAD aged between 18 and 50 years attending our university hospital between 2005 and 2015. Of the 87 patients included, 32 (36%) were women. Smoking was acknowledged by 81 patients (93%), and 37 had dyslipidemia (42.5%). Median follow-up was 24 months (10-59). Recurrence occurred in 41 patients (47.1%), all active smokers, with a median delay of 14 months (7-47). Acute limb ischemia at diagnosis was significantly associated with major amputation, odds ratio (OR) 5.95 (95%CI 1.41-40.90, P = .029), which was needed by 11 patients (12.6%). Treatments included antiplatelet therapy (76; 87.4%), statins (67; 77%), and anti-hypertensives (60; 69%), and 29 (32.1%) patients benefited from vascular rehabilitation. This cohort of relatively young patients with PAD showed a high level of symptom recurrence. Atherosclerosis was the most common etiology. Our study revealed that medical treatment is often under-prescribed in this age group and needs to be improved.

Novel Oral Anticoagulants in Peripheral Artery Disease: Current Evidence

2019 ◽  
Vol 24 (38) ◽  
pp. 4511-4515 ◽  
Author(s):  
A. Koutsoumpelis ◽  
C. Argyriou ◽  
K.M. Tasopoulou ◽  
E.I. Georgakarakos ◽  
G.S. Georgiadis
Keyword(s):  
Peripheral Artery Disease ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
Current Evidence ◽  
Peripheral Artery ◽  
Cardiac Events ◽  
Traditional Therapy ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Artery Disease

Background: Peripheral artery disease is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious. Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or unstable. Methods: The aim of this study is to review the current evidence with respect to recently published studies concerning the use of Novel anticoagulants in peripheral artery disease. Results: The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines propose the use of novel oral anticoagulants. Conclusion: For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.

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