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 Association of Hypertension and Arterial Blood Pressure on Limb and Cardiovascular Outcomes in Symptomatic Peripheral Artery Disease

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Marat Fudim ◽  
Charles W. Hopley ◽  
Zhen Huang ◽  
Sarah Kavanagh ◽  
Frank W. Rockhold ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Hazard Ratio ◽  
Peripheral Artery ◽  
Increased Risk ◽  
History Of ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background: Current guidelines recommend aggressive management of hypertension. Recent evidence suggested potential harm with low blood pressure targets in patients with peripheral artery disease. We investigated the association of a history of hypertension and office systolic blood pressure (SBP) with major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). Methods and Results: The EUCLID trial (Examining the Use of Ticagrelor in Peripheral Artery Disease) included 13 885 participants with symptomatic peripheral artery disease; median follow-up was 30 months. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for any MACE, MALE, and MALE including lower extremity revascularization. A clinical history of arterial hypertension was present in 10 857 (78%) participants, and these participants were older and more likely to be female when compared with the 3026 (22%) patients without hypertension. In patients with a history of hypertension, the adjusted hazard ratio for MACE was 0.94, 95% CI, 0.82–1.08; P =0.39, and the adjusted hazard ratio for MALE was 1.08, 95% CI, 0.96–1.23; P =0.21. During follow-up, average SBP was 135 mm Hg (125–145). Every 10 mmHg increase in SBP>125 mmHg was associated with an increased risk of MACE (HR, 1.10 [95% CI, 1.06–1.14]; P <0.001), a marginally increased risk of MALE (HR, 1.07 [95% CI, 1.00–1.15]; P =0.062), and an increased risk of MALE/lower extremity revascularization (HR, 1.08 [95% CI, 1.04–1.11]; P <0.001). Every decrease in 10 mmHg SBP ≤125 mmHg was associated with an increased risk of MACE (HR, 1.19 [95% CI, 1.09–1.31]; P <0.001) but not MALE or MALE/lower extremity revascularization (HR, 1.02 [95% CI, 0.84–1.23], P =0.824; HR, 1.04 [95% CI, 0.95–1.13], P =0.392, respectively). Conclusions: History of hypertension was not associated with higher hazard for MACE or MALE in patients with peripheral artery disease. In contrast, there was a higher hazard of MACE in patients with out-of-target low and high SBP. High but not low SBP was associated with an increased risk of ischemic limb events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

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.

Advances in Revascularization for Peripheral Artery Disease: Revascularization in PAD

2021 ◽  
Vol 128 (12) ◽  
pp. 1885-1912
Author(s):  
Joshua A. Beckman ◽  
Peter A. Schneider ◽  
Michael S. Conte
Keyword(s):  
Intermittent Claudication ◽  
Peripheral Artery Disease ◽  
Clinical Presentation ◽  
Rapid Development ◽  
Microvascular Disease ◽  
Limb Ischemia ◽  
Medical Emergency ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Artery Disease

Effective revascularization of the patient with peripheral artery disease is about more than the procedure. The approach to the patient with symptom-limiting intermittent claudication or limb-threatening ischemia begins with understanding the population at risk and variation in clinical presentation. The urgency of revascularization varies significantly by presentation; from patients with intermittent claudication who should undergo structured exercise rehabilitation before revascularization (if needed) to those with acute limb ischemia, a medical emergency, who require revascularization within hours. Recent years have seen the rapid development of new tools including wires, catheters, drug-eluting technology, specialized balloons, and biomimetic stents. Open surgical bypass remains an important option for those with advanced disease. The strategy and techniques employed vary by clinical presentation, lesion location, and lesion severity. There is limited level 1 evidence to guide practice, but factors that determine technical success and anatomic durability are largely understood and incorporated into decision-making. Following revascularization, medical therapy to reduce adverse limb outcomes and a surveillance plan should be put in place. There are many hurdles to overcome to improve the efficacy of lower extremity revascularization, such as restenosis, calcification, microvascular disease, silent embolization, and tools for perfusion assessment. This review highlights the current state of revascularization in peripheral artery disease with an eye toward technologies at the cusp, which may significantly impact current practice.

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 Clinical Significance of Ankle Systolic Blood Pressure Following Exercise in Assessing Calf Muscle Tissue Ischemia in Peripheral Artery Disease

Angiology ◽  
2012 ◽  
Vol 64 (5) ◽  
pp. 364-370 ◽  
Author(s):  
Aman Khurana ◽  
Julie A. Stoner ◽  
Thomas L. Whitsett ◽  
Suman Rathbun ◽  
Polly S. Montgomery ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Clinical Significance ◽  
Peripheral Artery Disease ◽  
Muscle Tissue ◽  
Calf Muscle ◽  
Peripheral Artery ◽  
Tissue Ischemia ◽  
Artery Disease

Simultaneous inter-arm and inter-leg systolic blood pressure differences to diagnose peripheral artery disease: a diagnostic accuracy study

2017 ◽  
Vol 27 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Ángel Herráiz-Adillo ◽  
Alba Soriano-Cano ◽  
José Alberto Martínez-Hortelano ◽  
Miriam Garrido-Miguel ◽  
Julián Ángel Mariana-Herráiz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diagnostic Accuracy ◽  
Systolic Blood Pressure ◽  
Peripheral Artery Disease ◽  
Diagnostic Accuracy Study ◽  
Peripheral Artery ◽  
Accuracy Study ◽  
Artery Disease

scholarly journals Ankle-Brachial Index for Risk Stratification in Patients With Symptomatic Peripheral Artery Disease With and Without Prior Lower Extremity Revascularization: Observations From the EUCLID Trial

2021 ◽  
Author(s):  
William R. Hiatt ◽  
Connie N. Hess ◽  
Marc P. Bonaca ◽  
Sarah Kavanagh ◽  
Manesh R. Patel ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Ankle Brachial Index ◽  
Cubic Spline ◽  
Hazard Ratio ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background: A reduced ankle-brachial index (ABI) is a measure of atherosclerosis and is associated with ischemic risk in the general population. Whether this relationship is maintained in peripheral artery disease after lower extremity revascularization (LER), which can modify ABI, is unknown. Methods: The EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) enrolled 13 885 patients with symptomatic peripheral artery disease; 57% with prior LER, and 43% with ABI ≤0.80. The primary major adverse cardiovascular events (MACE) outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Major adverse limb events (MALE) included acute limb ischemia and major amputation. An adjusted Cox proportional hazards model demonstrated a nonlinear relationship between ABI and outcomes. A restricted cubic spline model with 4 knots was developed to identify the best fitting model to describe the relationship between ABI and MACE and MALE risk. Results: Baseline ABI (mean±SD) was 0.77±0.21 in participants with prior LER and 0.63±0.14 in those without prior LER ( P <0.0001). There was no statistical interaction between prior LER and ABI, meaning the shapes of the cubic spline models were similar between groups. In those with prior LER, for every 0.10 unit lower ABI below an ABI of 1.00, the hazard ratio for MACE was 1.08 (95% CI, 1.04–1.12; P <0.0001), below an ABI of 0.80 the hazard ratio for MALE was 1.32 (95% CI, 1.21–1.43; P <0.0001). In patients without prior LER, every 0.10 unit lower ABI below an ABI of 0.70 was associated with increased risk for MACE (hazard ratio, 1.14 [95% CI, 1.06–1.23]; P =0.0004) and MALE (hazard ratio, 1.27 [95% CI, 1.08–1.49]; P =0.003). Conclusions: Patients with established peripheral artery disease, particularly those with prior LER, have an increased risk of MACE and MALE. The ABI remains a strong predictor of MACE and MALE ischemic events with an inverse relationship below an ABI threshold for patients with and without prior LER. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

scholarly journals 2017 ACC/AHA blood pressure classification and incident peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) Study

2019 ◽  
Vol 27 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Yifei Lu ◽  
Shoshana H Ballew ◽  
Hirofumi Tanaka ◽  
Moyses Szklo ◽  
Gerardo Heiss ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Peripheral Artery Disease ◽  
Cox Regression ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Stage 1

Aims The aim of this study was to evaluate the associations of blood pressure categorization based on the 2017 American College of Cardiology and American Heart Association guideline with the risk of peripheral artery disease (PAD). Methods Among 13,113 middle-aged participants, we investigated the associations of 2017 blood pressure categories (systolic <120 and diastolic <80 mmHg (normal if no anti-hypertensive medications; reference), 120–129 and <80 (elevated), 130–139 and/or 80–89 (stage 1 hypertension), and ≥140 and/or ≥90 (stage 2 hypertension)) with incident PAD (hospitalizations with a diagnosis or leg revascularization) using Cox regression models. Analyses were separately conducted in individuals with and without anti-hypertensive medications. Results During a median follow-up of 25.4 years, 466 incident PAD occurred (271 cases in 9858 participants without anti-hypertensive medications). In participants without anti-hypertensive medications, we observed significant hazard ratios of PAD in elevated blood pressure (1.80 (1.28–2.51)) and stage 2 hypertension (2.40 (1.72–3.34)), but not in stage 1 hypertension. Analyzing systolic and diastolic blood pressure separately, higher systolic blood pressure categories showed significant associations with incident PAD in a graded fashion whereas, for diastolic blood pressure, only ≥90 mmHg did. Generally similar patterns were seen among participants on anti-hypertensive medication, while they had higher risk of PAD than those without at each blood pressure category. Conclusions Systolic blood pressure, including the category of 130–139 mmHg, showed stronger associations with incident PAD than did diastolic blood pressure. Consequently, elevated blood pressure conferred similar or even greater risk of PAD than stage 1 hypertension, with implications on how to interpret new blood pressure categories in terms of leg vascular health.

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.

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