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

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.

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

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.

Outcomes with cilostazol after endovascular therapy of peripheral artery disease

2019 ◽  
Vol 24 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Michael Megaly ◽  
Bishoy Abraham ◽  
Marwan Saad ◽  
Andrew Mekaiel ◽  
Peter Soukas ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Endovascular Therapy ◽  
Lower Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Target Lesion ◽  
Major Amputation ◽  
Primary Patency ◽  
Peripheral Artery ◽  
Artery Disease

The role of cilostazol after endovascular therapy (EVT) of peripheral artery disease (PAD) remains unclear. We conducted a meta-analysis for all studies reporting the outcomes of cilostazol after EVT of PAD from January 2000 through November 2018 with the outcomes of interest including primary patency, major adverse limb events (MALE), target lesion revascularization (TLR), and major amputation. We included eight studies (three randomized controlled trials (RCTs) and five observational studies) with a total of 3846 patients (4713 lesions). During a mean follow-up duration of 12.5 ± 5 months, the use of cilostazol was associated with higher primary patency (OR 2.28, 95% CI (1.77, 2.94), p < 0.001, I2 = 24%), lower risk of TLR (OR 0.37, 95% CI (0.26, 0.52), p < 0.001, I2 = 0%), and lower risk of major amputation (OR 0.15, 95% CI (0.04, 0.62), p = 0.008, I2 = 0%). The use of cilostazol in RCTs was associated with significantly higher odds of primary patency compared with observational studies (OR 3.37 vs 2.28, p-interaction = 0.03). After further subgroup analysis, cilostazol remained associated with higher primary patency regardless of the use of anticoagulants (warfarin) ( p-interaction = 0.49). We conclude that the use of cilostazol after EVT of femoropopliteal and iliac lesions is associated with improved primary patency and lower risk of major amputation and TLR. The favorable impact of cilostazol is independent of the use of warfarin. PROSPERO identifier: CRD42018092715.

scholarly journals Protease-Resistant Stromal Cell–Derived Factor-1 for the Treatment of Experimental Peripheral Artery Disease

Circulation ◽  
2011 ◽  
Vol 123 (12) ◽  
pp. 1306-1315 ◽  
Author(s):  
Vincent F.M. Segers ◽  
Vyacheslav Revin ◽  
Weitao Wu ◽  
Helen Qiu ◽  
Zheng Yan ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Stromal Cell ◽  
Peripheral Artery ◽  
Stromal Cell Derived Factor ◽  
Artery Disease

Prognostic value of myeloperoxidase in patients with peripheral artery disease

Vascular ◽  
2020 ◽  
pp. 170853812095749
Author(s):  
Nadjib Schahab ◽  
Seyid Mansuroglu ◽  
Christian Schaefer ◽  
Rolf Fimmers ◽  
Georg Nickenig ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Vascular Disease ◽  
Peripheral Artery Disease ◽  
Prognostic Value ◽  
Target Lesion ◽  
Limb Ischaemia ◽  
Target Lesion Revascularisation ◽  
Peripheral Artery ◽  
Artery Disease

Objectives The involvement of myeloperoxidase in the production of dysfunctional high-density lipoproteins and oxidised biomolecules leads to oxidative stress in the blood vessel endothelium. This prospective cohort study aimed to examine the prognostic value of myeloperoxidase in patients with peripheral artery disease in relation to major adverse cardiac events (MACEs), target lesion revascularisation, and major adverse limb events (MALEs) and its association with multi-bed vascular disease, which is defined as any combination of the following: peripheral artery disease and coronary artery disease. Methods Myeloperoxidase levels were measured in patients with peripheral artery disease and coronary artery disease during angiography. A total of 94 patients were analysed and followed up regarding their MACEs, target lesion revascularisation, and MALEs from August 2016 until February 2019. Results Among patients with peripheral artery disease, the rates of MACE and mortality were higher in patients with high myeloperoxidase levels than in those with low myeloperoxidase levels; the myeloperoxidase levels were 3.68 times higher in these patients ( p < 0.0001). Patients with peripheral artery disease and coronary artery disease (multi-bed vascular disease) had higher myeloperoxidase levels than those with only peripheral artery disease and only coronary artery disease (one-bed vascular disease). Peripheral artery disease patients with higher myeloperoxidase levels had significantly higher rates of limb ischaemia, requiring further revascularisation than those with low myeloperoxidase levels. Conclusions High myeloperoxidase levels suggest poor outcomes and are associated with MACE and limb ischaemia. Our findings indicated that myeloperoxidase levels could become a prognostic marker and may be used in conjunction with other methods for risk stratification in patients with peripheral artery disease and multi-bed vascular disease.

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.

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

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

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

2018 ◽  
Vol 7 (2) ◽  
Author(s):  
Shipra Arya ◽  
Zachary Binney ◽  
Anjali Khakharia ◽  
Luke P. Brewster ◽  
Phil Goodney ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Peripheral Artery Disease ◽  
Major Amputation ◽  
Peripheral Artery ◽  
Artery Disease

Significant prevalence of peripheral artery disease in patients with disturbed wound healing following elective foot and ankle surgery: Results from the ABI-PRIORY (ABI as a PRedictor of Impaired wound healing after ORthopedic surgerY) trial

2019 ◽  
Vol 25 (2) ◽  
pp. 118-123
Author(s):  
Arne M Müller ◽  
Andreas Toepfer ◽  
Norbert Harrasser ◽  
Bernhard Haller ◽  
Markus Walther ◽  
...  
Keyword(s):  
Wound Healing ◽  
Risk Factor ◽  
Peripheral Artery Disease ◽  
Wound Complications ◽  
Control Group ◽  
Foot And Ankle ◽  
Peripheral Artery ◽  
Impaired Wound Healing ◽  
Ankle Surgery ◽  
Artery Disease

Disturbed wound healing (DWH) following elective foot and ankle surgery is associated with a number of known risk factors. The purpose of this study was to determine if peripheral artery disease (PAD) is a potential risk factor that contributes to an increase in postoperative DWH. In a case–control study, we analyzed all patients undergoing elective foot and ankle surgery between January 1, 2014 and December 31, 2017 at two institutions and identified 51 patients with postoperative DWH. After matching with 51 control patients without DWH, all 102 patients were evaluated for PAD. The prevalence of PAD was significantly higher in the DWH group compared to the control group (41.2% vs 19.6%, p < 0.01). This difference was even more distinctive for patients with any abnormal ankle–brachial index (ABI) (51.0% vs 19.6%, p < 0.001). After adjustment for diabetes, hypertension, hypercholesterolemia, and smoking, any abnormal ABI or a history of PAD remained an independent risk factor for DWH (odds ratio 3.28; 95% CI 1.24–8.71). In this dual-center study, postoperative DWH was associated with significantly higher rates of PAD. These findings suggest that preoperative evaluation for PAD could be a helpful tool to identify patients at high risk for postoperative wound complications undergoing foot and ankle surgery. This trial is registered with drks.de, number DRKS00012580.

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