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.

scholarly journals Review of biologic and behavioral risk factors linking depression and peripheral artery disease

2018 ◽  
Vol 23 (5) ◽  
pp. 478-488 ◽  
Author(s):  
Joel L Ramirez ◽  
Laura M Drudi ◽  
S Marlene Grenon
Keyword(s):  
Risk Factors ◽  
Peripheral Artery Disease ◽  
Current Evidence ◽  
Perioperative Outcomes ◽  
Behavioral Risk Factors ◽  
Behavioral Risk ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease ◽  
Coagulation Dysfunction

The incidence of depression has been rising rapidly, and depression has been recognized as one of the world’s leading causes of disability. More recently, depression has been associated with an increased risk of symptomatic atherosclerotic disease as well as worse perioperative outcomes in patients with cardiovascular disease. Additionally, recent studies have demonstrated an association between depression and peripheral artery disease (PAD), which has been estimated to affect more than 200 million people worldwide. These studies have identified that depression is associated with poor functional and surgical outcomes in patients with PAD. Although the directionality and specific mechanisms underlying this association have yet to be clearly defined, several biologic and behavioral risk factors have been identified to play a role in this relationship. These factors include tobacco use, physical inactivity, medical non-adherence, endothelial and coagulation dysfunction, and dysregulation of the hypothalamic-pituitary-adrenal axis, autonomic system, and immune system. In this article, we review these potential mechanisms and the current evidence linking depression and PAD, as well as future directions for research and interventional strategies. Understanding and elucidating this relationship may assist in preventing the development of PAD and may improve the care that patients with PAD and comorbid depression receive.

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 Anticoagulation in Peripheral Artery Disease: Are We There Yet?

2020 ◽  
Vol 3 ◽  
Author(s):  
Alessandro Cannavale ◽  
Mariangela Santoni ◽  
Giuseppe Cannavale ◽  
Fabrizio Fanelli
Keyword(s):  
Peripheral Artery Disease ◽  
Controlled Trial ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Peripheral Artery ◽  
Unfractioned Heparin ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Artery Disease ◽  
Randomised Controlled

Thromboembolism in patients with peripheral artery disease (PAD) represents a common cause of morbidity and mortality. In this article, the authors analyse the use of anticoagulants for patients with PAD. Anticoagulants have been used to reduce the risk of venous thromboembolism, but have recently been applied to the arterial circulation. Heparins were introduced to reduce short-term major adverse limb events in patients undergoing arterial revascularisation. Low molecular weight heparins have allowed easier management and carry a lower risk of bleeding than unfractioned heparin. Vitamin K anticoagulants have been tested in trials that included patients with PAD, showing an increased risk of bleeding when compared with aspirin alone, but longer patency rates for venous surgical bypass, although the evidence remains weak. Those anticoagulants are currently recommended only in patients with PAD who need anticoagulation for other diseases. Direct oral anticoagulants have only recently been investigated for use in patients with PAD. Promising results from low dose rivaroxaban plus aspirin have been recently outlined by a randomised controlled trial and supported by international guidelines.

A Targeted Literature Review of the Disease Burden in Patients With Symptomatic Peripheral Artery Disease

Angiology ◽  
2019 ◽  
Vol 71 (4) ◽  
pp. 303-314
Author(s):  
Rupert Bauersachs ◽  
Sebastian Debus ◽  
Mark Nehler ◽  
Maria Huelsebeck ◽  
Janita Balradj ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Disease Burden ◽  
Ankle Brachial Index ◽  
Peripheral Artery ◽  
Economic Burden Of Disease ◽  
Surgical Interventions ◽  
Treatment Practice ◽  
Patient Profile ◽  
Increased Risk ◽  
Artery Disease

Patients with peripheral artery disease (PAD) have an increased risk of cardiovascular (CV) and limb events, but the disease is frequently underdiagnosed and treatment options are limited. This review examines the disease burden of symptomatic PAD as well as key guideline recommendations. Publications were identified using the ProQuest portal to access the Medline, Medline In-Process, and Embase databases. Search terms for symptomatic PAD were combined with terms relevant to epidemiology, burden, treatment practice, and physiopathology. Articles in English published between January 2001 and September 2016 were screened according to the population, interventions, comparator, outcomes, and study design criteria. Relevant publications (n = 200) were identified. The reported incidence and prevalence of PAD varied depending on the definitions used and the study populations. Patients generally had a poor prognosis, with an increased risk of mortality, CV, and limb events and decreased quality of life. Guideline recommendations included ankle–brachial index measurements, exercise testing, and angiography for diagnosis and risk factor modification, antiplatelets, cilostazol, exercise therapy, or surgical interventions for treatment, depending on the patient profile. The clinical, humanistic, and economic burden of disease in patients with symptomatic PAD is substantial and needs to be reduced through improved PAD management.

scholarly journals Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Elena M. Yubero-Serrano ◽  
Juan F. Alcalá-Diaz ◽  
Francisco M. Gutierrez-Mariscal ◽  
Antonio P. Arenas-de Larriva ◽  
Patricia J. Peña-Orihuela ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Secondary Prevention ◽  
Peripheral Artery Disease ◽  
Cholesterol Efflux ◽  
Newly Diagnosed ◽  
Peripheral Artery ◽  
Cholesterol Efflux Capacity ◽  
Increased Risk ◽  
Artery Disease

Abstract Background Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. Methods CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. Results The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. Conclusions Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00924937. Unique Identifier: NCT00924937

scholarly journals Genetic Variation in Blood Pressure and Lifetime Risk of Peripheral Artery Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Michael G Levin ◽  
Derek Klarin ◽  
Venexia M Walker ◽  
Dipender Gill ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Peripheral Artery Disease ◽  
Genetic Correlations ◽  
Channel Blockers ◽  
Peripheral Artery ◽  
Antihypertensive Medications ◽  
Increased Risk ◽  
Genes Encoding ◽  
Artery Disease

Aims: We aimed to estimate the effect of blood pressure and blood pressure lowering medications (via genetic proxies) on peripheral artery disease. Methods and Results: GWAS summary statistics were obtained for BP (International Consortium for Blood Pressure + UK Biobank GWAS; N = up to 757,601 individuals), peripheral artery disease (PAD; VA Million Veteran Program; N = 24,009 cases, 150,983 controls), and coronary artery disease (CAD; CARDIoGRAMplusC4D 1000 Genomes; N = 60,801 cases, 123,504 controls). Genetic correlations between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and CAD and PAD were estimated using LD score regression. The strongest correlation was between SBP and CAD (rg = 0.36; p = 3.9 x 10-18). Causal effects were estimated by two-sample MR using a range of pleiotropy-robust methods. Increased SBP, DBP, and PP increased risk of both PAD (SBP OR 1.25 [1.19-1.31] per 10mmHg increase, p = 3 x 10-18; DBP OR 1.27 [1.17-1.39], p = 4 x 10-8; PP OR 1.51 [1.38-1.64], p = 1 x 10-20) and CAD (SBP OR 1.37 [1.29-1.45], p = 2 x 10-24; DBP OR 1.6 [1.45-1.76], p = 7 x 10-22; PP OR 1.56 [1.4-1.75], p = 1 x 10-15). The effects of SBP and DBP were greater for CAD than PAD (pdiff = 0.024 for SBP, pdiff = 4.9 x 10-4 for DBP). Increased liability to PAD increased PP (beta = 1.04 [0.62-1.45] mmHg per 1 unit increase in log-odds in liability to PAD, p = 1 x 10-6). MR was also used to estimate the effect of BP lowering through different classes of antihypertensive medications using genetic instruments containing BP-trait associated variants located within genes encoding protein targets of each medication. SBP lowering via calcium channel blocker-associated variants was protective of CAD (OR 0.38 per 10mmHg decrease in SBP; 95% CI 0.19-0.77; p = 0.007). Conclusions: Higher BP is likely to cause both PAD and CAD but may have a larger effect on CAD risk. BP-lowering through calcium-channel blockers (as proxied by genetic variants) decreased risk of CAD.

scholarly journals Serum resistin is associated with impaired endothelial function and a higher rate of adverse cardiac events in patients with peripheral artery disease

2019 ◽  
Vol 69 (2) ◽  
pp. 497-506 ◽  
Author(s):  
Joel L. Ramirez ◽  
Sukaynah A. Khetani ◽  
Greg J. Zahner ◽  
Kimberly A. Spaulding ◽  
Melinda S. Schaller ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Cardiac Events ◽  
Adverse Cardiac Events ◽  
Artery Disease

Abstract 3073: Metabolic Syndrome, Inflammation and Risk of Symptomatic Peripheral Artery Disease in Women: A Prospective Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
David Conen ◽  
Kathryn M Rexrode ◽  
Paul M Ridker ◽  
Aruna D Pradhan
Keyword(s):  
Metabolic Syndrome ◽  
Peripheral Artery Disease ◽  
Cox Proportional Hazards ◽  
Health Study ◽  
Intercellular Adhesion Molecule ◽  
Peripheral Artery ◽  
Risk Increase ◽  
Increased Risk ◽  
Multivariable Models ◽  
Artery Disease

Background Metabolic syndrome (MetS) includes a number of cardiovascular risk factors known to predict vascular disease. Little is known, however, about the interrelationships between MetS, inflammation and the risk of incident peripheral artery disease (PAD). Methods We conducted a prospective cohort study among 27111 women participating in the Women’s Health Study. Subjects were free of cardiovascular disease at baseline and followed for the incidence of symptomatic PAD (n=114) over a follow-up period of 13.3 years. We used Cox proportional-hazards models to compare the risk of PAD among women with and without the MetS. We also evaluated relationships between MetS and markers of subclinical inflammation including high sensitivity C-reactive protein (hsCRP) and soluble intercellular adhesion molecule-1 (sICAM-1) and adjusted for these biomarker levels in multivariable models. Results At study entry, 25.5% of participants had the MetS. Women with the MetS had a 62% increased risk of incident PAD (HR 1.62; 95% CI 1.10 –2.38). After multivariable adjustment, MetS remained significantly associated with incident PAD (Table ). Similar results were obtained when we assessed the risk of PAD according to the number of MetS defining traits (21% risk increase per additional trait) (Table ). Median plasma levels of hsCRP and sICAM-1 were 4.0 mg/L versus 1.53 mg/L (p<0.0001) and 374 ng/mL versus 333 ng/mL (p<0.0001) in women with and without MetS, respectively. From 0 to 5 MetS defining traits, median hsCRP levels gradually increased from 1.0 to 5.9 mg/L (p<0.0001) and median sICAM-1 levels increased from 321 to 413 ng/mL (p<0.0001). When hsCRP and sICAM-1 were added to multivariable models for incident PAD, risk estimates for the MetS were substantially attenuated and became non-significant (Table ). Conclusion Women with the MetS have an increased risk of incident PAD. This increased risk may be largely mediated by the effects of inflammation and/or endothelial activation. Metabolic Syndrome and Risk of PAD

Abstract MP14: Proteinuria is Associated With a Greater Risk of Lower Limb Amputation in Patients With Peripheral Artery Disease

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Jung-Im Shin ◽  
Morgan Grams ◽  
Josef Coresh ◽  
Alex Chang ◽  
Kunihiro Matsushita
Keyword(s):  
Peripheral Artery Disease ◽  
Lower Limb ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Lower Limb Amputation ◽  
Limb Amputation ◽  
Antiplatelet Drug ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Introduction: Proteinuria is shown to be associated with increased risk of peripheral artery disease (PAD). However, its association with the risk of lower limb amputation in patients with PAD is unknown. Hypothesis: We hypothesized that proteinuria is associated with the risk of amputation in patients with PAD in a graded fashion. Methods: We identified 3,388 PAD patients with data on urine dipstick proteinuria within two years prior to PAD diagnosis between 1997 and 2017 in the Geisinger Health System (mean age 69.7 years, 44.8% female, 97.4% non-Hispanic White, 57.8% diabetic). We quantified the association of proteinuria with the risk of amputation using Cox proportional hazards models, adjusting for demographics, calendar year, estimated glomerular filtration rate, HbA1c, comorbidities including diabetic retinopathy/neuropathy, and medication use (antiplatelet drug, statin, and renin-angiotensin system inhibitor). Results: There were 55.2% with negative dipstick proteinuria, 11.1% trace, 14.1% with 1+, and 19.5% with ≥2+. A total of 245 patients underwent amputations over a median follow-up of 3.4 years. Incidence rate of amputation was 1.15 per 100 person-years for dipstick negative, 1.47 for trace, 2.11 for 1+, and 3.78 for ≥2+. This dose-response relationship remained similar even after accounting for potential confounders (p-trend=0.015), with particularly evident association for ≥2+ of dipstick (an adjusted hazard ratio of 1.52 [95% confidence interval: 1.08-2.17, p=0.017) (Figure). When we added proteinuria to other covariates, the risk discrimination slightly improved (Δc-statistic 0.007 [0.001-0.014]). Conclusions: Higher proteinuria was associated with a greater risk of lower limb amputation among patients with newly diagnosed PAD. Our results suggest the importance of considering proteinuria in risk assessment of limb loss in PAD patients.

scholarly journals P1234SNF472 IMPROVES LIMB BLOOD PERFUSION AND WALKING ABILITY IN A PERIPHERAL ARTERY DISEASE VASCULAR CALCIFICATION RAT MODEL

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Firas Bassissi ◽  
Miguel David Ferrer Reynes ◽  
M Mar Pérez ◽  
Joan Perelló ◽  
Carolina Salcedo
Keyword(s):  
Peripheral Artery Disease ◽  
Vascular Calcification ◽  
Rat Model ◽  
Blood Perfusion ◽  
Walking Distance ◽  
Arterial Calcification ◽  
Walking Ability ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Abstract Background and Aims Peripheral Artery disease (PAD) is a common vascular disease associated with functional impairment and increased risk of cardiovascular events in End Stage Kidney Disease (ESKD) patients undergoing dialysis. Poor limb salvage outcomes and high post-amputation mortality in hemodialysis (HD) patients highlight the need for earlier medical therapies. Cilostazol and pentoxifylline are approved for PAD. Their use in HD patients stays limited and cilostazol use requires caution in this population. Clinical studies demonstrate associations between arterial calcification and adverse outcomes in PAD patients. SNF472, a selective calcification inhibitor that interferes in the formation and growth of hydroxyapatite, is in Phase 3 for calciphylaxis treatment. This study aims to evaluate the effects of SNF472 on limb functional recovery and blood perfusion in a Vitamin D3 (VitD)-induced arterial calcification rat model. Method Arterial calcification was induced in 32 Sprague Dawley rats by 3 consecutive daily s.c. doses of 120 kIU/kg VitD. Rats were divided into four groups and treated during 12 days by: placebo s.c, placebo p.o, SNF472 (20 mg/kg/day, s.c.) or cilostazol (20 mg/kg/day, p.o.). An additional group of 8 rats without VitD received vehicle only (sham). Efficacy was evaluated at day 12 and 17 (5 days after treatment stop). Posterior limb blood perfusion was measured using Laser Doppler Imaging and limb walking ability was evaluated by measuring Maximum Walking Distance (MWD) and Maximum Walking Time (MWT) using a treadmill. Rats were sacrificed at day 26 (14 days after treatment stop), and aortas were collected for calcium analysis. Results VitD-induced arterial calcification was associated with decreased blood perfusion and impairment of limb walking ability (MWT and MWD) compared to sham. SNF472 reduced aorta calcification by 41% compared to placebo. No effects of cilostazol on vascular calcification were observed. The inhibition of calcification in SNF472-treated animals was associated with significant higher limb blood perfusion compared to placebo or Cilostazol (1.28 and 1.37-fold higher, respectively at day 12: p&lt; 0.001) and it was translated into a significant improvement in walking ability compared to placebo (515±114 meters vs 334±187 meters, respectively: p&lt;0.05). Conclusion SNF472 shows improvements in vascular calcification, blood perfusion and a functional parameter like walking distance in a PAD vascular calcification rat model. These results suggest that SNF472 may represent a new therapeutic approach for the treatment of PAD associated with high vascular calcification such as in renal disease.

Sign in / Sign up

Export Citation Format

Share Document