scholarly journals Acute Limb Ischemia and Outcomes With Vorapaxar in Patients With Peripheral Artery Disease: Results From the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis in Myocardial Infarction 50 (TRA2°P-TIMI 50)

2016 ◽  
Vol 63 (6) ◽  
pp. 1663
Author(s):  
M.P. Bonaca ◽  
J.A. Gutierrez ◽  
M.A. Creager
2021 ◽  
Vol 128 (12) ◽  
pp. 1885-1912
Author(s):  
Joshua A. Beckman ◽  
Peter A. Schneider ◽  
Michael S. Conte

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.


2022 ◽  
Vol 27 ◽  
pp. 107424842110561
Author(s):  
Justin T. Morrison ◽  
Nicholas Govsyeyev ◽  
Connie N. Hess ◽  
Marc P. Bonaca

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.


Circulation ◽  
2016 ◽  
Vol 133 (10) ◽  
pp. 997-1005 ◽  
Author(s):  
Marc P. Bonaca ◽  
J. Antonio Gutierrez ◽  
Mark A. Creager ◽  
Benjamin M. Scirica ◽  
Jeffrey Olin ◽  
...  

Circulation ◽  
2019 ◽  
Vol 140 (7) ◽  
pp. 556-565 ◽  
Author(s):  
Connie N. Hess ◽  
Zhen Huang ◽  
Manesh R. Patel ◽  
Iris Baumgartner ◽  
Jeffrey S. Berger ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (23) ◽  
pp. 2219-2230
Author(s):  
William R. Hiatt ◽  
Marc P. Bonaca ◽  
Manesh R. Patel ◽  
Mark R. Nehler ◽  
Eike Sebastian Debus ◽  
...  

Background: The VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated superiority of rivaroxaban plus aspirin versus aspirin to reduce major cardiac and ischemic limb events after lower extremity revascularization. Clopidogrel is commonly used as a short-term adjunct to aspirin after endovascular revascularization. Whether clopidogrel modifies the efficacy and safety of rivaroxaban has not been described. Methods: VOYAGER PAD was a phase 3, international, double-blind, placebo-controlled trial in patients with symptomatic PAD undergoing lower extremity revascularization randomized to rivaroxaban 2.5 mg twice daily plus 100 mg aspirin daily or rivaroxaban placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was TIMI (Thrombolysis in Myocardial Infarction) major bleeding, with International Society on Thrombosis and Haemostasis major bleeding a secondary safety outcome. Clopidogrel use was allowed at the discretion of the investigator for up to 6 months after the qualifying revascularization. Results: Of the randomized patients, 3313 (50.6%) received clopidogrel for a median duration of 29.0 days. Over 3 years, the hazard ratio for the primary outcome of rivaroxaban versus placebo was 0.85 (95% CI, 0.71–1.01) with clopidogrel and 0.86 (95% CI, 0.73–1.01) without clopidogrel without statistical heterogeneity ( P for interaction=0.92). Rivaroxaban resulted in an early apparent reduction in acute limb ischemia within 30 days (hazard ratio, 0.45 [95% CI, 0.14–1.46] with clopidogrel; hazard ratio, 0.48 [95% CI, 0.22–1.01] without clopidogrel; P for interaction=0.93). Compared with aspirin, rivaroxaban increased TIMI major bleeding similarly regardless of clopidogrel use ( P for interaction=0.71). With clopidogrel use >30 days, rivaroxaban was associated with more International Society on Thrombosis and Haemostasis major bleeding within 365 days (hazard ratio, 3.20 [95% CI, 1.44–7.13]) compared with shorter durations of clopidogrel ( P for trend=0.06). Conclusions: In the VOYAGER PAD trial, rivaroxaban plus aspirin reduced the risk of adverse cardiovascular and limb events with an early benefit for acute limb ischemia regardless of clopidogrel use. The safety of rivaroxaban was consistent regardless of clopidogrel use but with a trend for more International Society on Thrombosis and Haemostasis major bleeding with clopidogrel use >30 days than with a shorter duration. These data support the addition of rivaroxaban to aspirin after lower extremity revascularization regardless of concomitant clopidogrel, with a short course (≤30 days) associated with less bleeding. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02504216.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
W Hiatt ◽  
C W Hopley ◽  
S Kavanagh ◽  
M R Patel ◽  
I Baumgartner ◽  
...  

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


Author(s):  
Connie N. Hess ◽  
E. Sebastian Debus ◽  
Mark R. Nehler ◽  
Sonia S. Anand ◽  
Manesh R. Patel ◽  
...  

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.


Angiology ◽  
2021 ◽  
pp. 000331972110421
Author(s):  
Simon Soudet ◽  
Lorène Bultel ◽  
Lamrani Adnane ◽  
Thierry Reix ◽  
Marie Antoinette Sevestre

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.


Vascular ◽  
2020 ◽  
pp. 170853812095885
Author(s):  
S Michael Gharacholou ◽  
Zhuo Li ◽  
Jonathan J Uy ◽  
Lee H Eckstein ◽  
Carolyn R Flock ◽  
...  

Background There are limited data on outcomes for patients with peripheral artery disease undergoing endovascular revascularization by multi-disciplinary teams in a community hospital setting. Methods From January 2015 through December 2015, we assembled a multi-disciplinary program comprised of cardiologists, surgeons, radiologists, nurses, and administrative staff for managing patients with peripheral artery disease undergoing endovascular revascularization. Demographic, procedural, and outcomes data were collected with use of a template from the Society for Vascular Surgery Vascular Quality Initiative database. We compared characteristics and outcomes of patients with intermittent claudication and critical limb ischemia. We used Kaplan–Meier methods to estimate the rate of overall survival and freedom from rehospitalization between groups. Results After excluding patients with acute limb ischemia ( n = 5), peripheral intervention to the upper extremity ( n = 6), or abdominal aorta ( n = 11), there were 82 patients in the study cohort; 45 had intermittent claudication and 37 had critical limb ischemia. Baseline and procedural characteristics were similar between groups, although critical limb ischemia patients were more likely to have hyperlipidemia (75.7% vs. 53.3%, P = .42). Procedural success was achieved in 91.3% of cases. Actionable access site bleeding occurred in 2.4% of patients. High rates of aspirin (91.5%) and statin (87.8%) were noted at discharge. After two years of post endovascular revascularization, survival was 57.5% for critical limb ischemia patients and 94.4% for intermittent claudication patients ( P < .001). Freedom from rehospitalization was 32.7% for critical limb ischemia patients and 83.5% for intermittent claudication patients ( P < .001). Conclusions We found that favorable outcomes may be achieved with a multi-disciplinary peripheral artery disease program at community hospitals. The incorporation of quality improvement practices may further help to develop standardized and regionalized approaches to care delivery for patients with peripheral artery disease.


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