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BACKGROUND: Rivaroxaban plus aspirin compared with aspirin alone reduced major cardiac and ischemic limb events after lower extremity revascularization (LER) in the VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) trial. The effect has not been described in patients undergoing endovascular LER. METHODS: The VOYAGER PAD trial randomized 6564 patients with symptomatic peripheral artery disease to a double-blinded treatment with 2.5 mg of rivaroxaban BID or matching placebo and 100 mg of aspirin daily. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular pathogenesis, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was Thrombolysis in Myocardial Infarction major bleeding. A prespecified subgroup of patients who underwent endovascular revascularization was included. RESULTS: Endovascular LER occurred in 4379 (66.7%) patients and surgical LER in 2185 (33.3%). Over a 3-year follow-up, rivaroxaban reduced the risk of the primary outcome by 15% (hazard ratio [HR], 0.85 [95% CI, 0.76–0.96]) with an absolute risk reduction of 0.92% at 6 months and 1.04% at 3 years and a consistent benefit in those receiving endovascular (HR, 0.89 [95% CI, 0.76–1.03]) or surgical LER (HR, 0.81 [95% CI, 0.67–0.98]; P interaction=0.43). For endovascular-treated patients, rivaroxaban reduced the risk of acute limb ischemia or major amputation of a vascular pathogenesis by 30% (HR, 0.70 [95% CI, 0.54–0.90]; P =0.005) with an absolute risk reduction of 1.0% at 6 months and 2.0% at 3 years compared with aspirin alone. Among endovascular-treated patients, the median duration of concomitant dual antiplatelet therapy with clopidogrel treatment was 31 days (interquartile range, 30–58). There was a consistent benefit for rivaroxaban regardless of background clopidogrel. Thrombolysis in Myocardial Infarction major bleeding was significantly higher for the rivaroxaban and aspirin group for the endovascular cohort (HR, 1.66 [95% CI, 1.06–2.59]) with an absolute risk increase of 0.9% at 3 years with no increase in intracranial or fatal bleeding observed (HR, 0.86 [95% CI, 0.40–1.87]; P =0.71). Mortality with rivaroxaban was higher in the endovascular-treated patients (HR, 1.24 [95% CI, 1.02–1.52]), although this finding was isolated to specific regions. CONCLUSIONS: Rivaroxaban added to aspirin or dual antiplatelet therapy after LER for peripheral artery disease reduces ischemic risk and increases major bleeding without an increased risk of intracranial or fatal bleeding. These benefits are consistent in those treated with endovascular and surgical approaches with significant benefits for major adverse limb events. These data support the use of rivaroxaban in addition to aspirin or dual antiplatelet therapy after endovascular intervention for symptomatic peripheral artery disease. [ABSTRACT FROM AUTHOR]

The article titled "Unplanned Index Limb Revascularization With Rivaroxaban Versus Placebo in Patients With Critical Limb-Threatening Ischemia After Endovascular and Surgical Treatment: Insights From VOYAGER PAD" discusses the results of the VOYAGER PAD study, which examined the efficacy of rivaroxaban in reducing ischemic events, including unplanned index limb revascularization (UILR), in patients undergoing lower-extremity revascularization (LER) for symptomatic peripheral artery disease (PAD). The study found that rivaroxaban reduced UILR by 22% in patients with critical limb-threatening ischemia (CLTI), regardless of the initial LER method (surgical or endovascular). The findings suggest that rivaroxaban may be beneficial in reducing repeat revascularization in patients with CLTI. However, it is important to note that the trial was not powered to show statistical significance for the UILR endpoint within the subgroups presented. [Extracted from the article]

Peripheral artery disease (PAD) affects 200 million individuals worldwide. In the United States, certain demographic groups experience a disproportionately higher prevalence and clinical effect of PAD. The social and clinical effect of PAD includes higher rates of individual disability, depression, minor and major limb amputation along with cardiovascular and cerebrovascular events. The reasons behind the inequitable burden of PAD and inequitable delivery of care are both multifactorial and complex in nature, including systemic and structural inequity that exists within our society. Herein, we present an overview statement of the myriad variables that contribute to PAD disparities and conclude with a summary of potential novel solutions. [ABSTRACT FROM AUTHOR]

Background: Patients with peripheral arterial disease (PAD) are at increased risk of cardiovascular morbidity and mortality. Medical prevention with antithrombotic and statin therapies is a mainstay of treatment to prevent adverse outcomes; nevertheless, patients with PAD are often undertreated. This study describes the temporal changes in medical prevention and adverse outcomes in a national cohort of patients with symptomatic PAD after revascularization.Methods: We identified all patients with a first open surgical or endovascular revascularization procedure in the lower extremities or abdomen in Denmark, from 2000 to 2016. We examined temporal changes in the use of aspirin, clopidogrel, and statins and 1-year cause-specific hazard ratios for adverse clinical outcomes, after adjusting for procedure type, treatment indication, age, sex, and cardiovascular risk factors. The analyses were performed overall and within strata of index procedure (endovascular versus surgical), treatment indication, age, sex, and high-risk comorbidities.Results: Between 2000 and 2016, we identified 32 911 patients who underwent revascularization for symptomatic PAD. The mean age was 69 years and increased over time, as did the burden of comorbidity. The cumulative incidence of medication use increased between 2000 to 2004 and 2013 to 2016, respectively, from 57.3% to 64.3% for aspirin, 3.6% to 24.8% for clopidogrel, and 36.2% to 77.1% for statins. Concurrently, the 1-year outcome rates declined. Compared with 2000 to 2004, the adjusted hazard ratios in 2013 to 2016 were 0.73 (95% CI, 0.62-0.84) for major adverse cardiovascular events, 0.92 (95% CI, 0.85-1.00) for major adverse limb events, 0.60 (95% CI, 0.48-0.74) for myocardial infarction, 0.94 (95% CI, 0.75-1.18) for ischemic stroke, 0.92 (95% CI, 0.75-1.12) for major bleeding, 0.54 (95% CI, 0.39-0.76) for cardiovascular death, and 0.80 (95% CI, 0.72-0.88) for all-cause death. These improvements in prognosis were most prominent from 2000 to 2004 to 2005 to 2008 and occurred in all strata of index procedure, treatment indication, sex, age, and comorbidity. In contrast, the adjusted hazard ratio for major amputations was 1.00 (95% CI, 0.90-1.11) when comparing 2013 to 2016 to 2000 to 2004.Conclusions: Medical prevention of adverse events has increased considerably over time in patients who underwent revascularization for symptomatic PAD. This increase was accompanied by reductions in all adverse outcomes, except major amputations. [ABSTRACT FROM AUTHOR]

Paclitaxel drug-coated balloons and drug-eluting stents became commercially available for the treatment of intermittent claudication in 2015 and 2012, respectively. Both devices demonstrated superiority in limb revascularization compared with non-paclitaxel-coated devices and were rapidly accepted into clinical practice. In a recent systematic review and study-level meta-analysis, Katsanos et al reported a late all-cause mortality signal for patients in the drug-coated balloon and drug-eluting stent arms of randomized clinical trials for both devices. As a result of this safety signal, Vascular InterVentional Advances Physicians (VIVA), a not-for-profit 501c(3) organization, convened the Vascular Leaders Forum on March 1 and 2, 2019, in Washington, DC, to initiate an open and collaborative process of investigation into this finding. The Vascular Leaders Forum brought together 100 stakeholders, including an international group of representatives of cardiovascular medicine, interventional radiology, vascular medicine, and vascular surgery; oncologists; basic scientists; the Food and Drug Administration; the Centers for Medicare and Medicaid Services; and commercial manufacturers of these products. The Vascular Leaders Forum reviewed the natural history of peripheral arterial disease, the use of paclitaxel in peripheral arterial disease and other conditions, the harm signal noted by Katsanos et al, the impact of the methods chosen by Katsanos et al, possible mechanisms of harm, the role of the Food and Drug Administration in a setting like this one, and guidance for clinicians taking care of patients with symptomatic peripheral arterial disease. This document integrates the most current data to help establish an appropriate path forward to understand the risks and benefits associated with these technologies while ensuring the best treatment paradigm for patients. [ABSTRACT FROM AUTHOR]

There are >12 million patients with peripheral artery disease in the United States. The most severe form of peripheral artery disease is critical limb ischemia (CLI). The diagnosis and management of CLI is often challenging. Ethnic differences in comorbidities and presentation of CLI exist. Compared with white patients, black and Hispanic patients have higher prevalence rates of diabetes mellitus and chronic renal disease and are more likely to present with gangrene, whereas white patients are more likely to present with ulcers and rest pain. A thorough evaluation of limb perfusion is important in the diagnosis of CLI because it can not only enable timely diagnosis but also reduce unnecessary invasive procedures in patients with adequate blood flow or among those with other causes for ulcers, including venous, neuropathic, or pressure changes. This scientific statement discusses the current tests and technologies for noninvasive assessment of limb perfusion, including the ankle-brachial index, toe-brachial index, and other perfusion technologies. In addition, limitations of the current technologies along with opportunities for improvement, research, and reducing disparities in health care for patients with CLI are discussed. [ABSTRACT FROM AUTHOR]

Background: Acute limb ischemia (ALI) is an important clinical event and an emerging cardiovascular clinical trial outcome. Risk factors for and outcomes after ALI have not been fully evaluated.Methods: EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized patients with peripheral artery disease to ticagrelor versus clopidogrel. Enrollment criteria included an ankle-brachial index ≤0.80 or previous lower extremity revascularization. Patients were grouped according to the primary outcome, postrandomization ALI hospitalization. Baseline factors associated with ALI were identified using Cox proportional hazards modeling. Models with ALI hospitalization as a time-dependent covariate were developed for secondary outcomes of major adverse cardiovascular events (myocardial infarction, cardiovascular death, ischemic stroke), all-cause mortality, and major amputation.Results: Among 13 885 patients, 1.7% (n=232) had 293 ALI hospitalizations (0.8 per 100 patient-years). Patients with versus without ALI were younger and more often had previous peripheral revascularization and lower baseline ankle-brachial index. Treatment during ALI hospitalization included endovascular revascularization (39.2%, n=115), surgical bypass (24.6%, n=72), and major amputation (13.0%, n=38). After multivariable adjustment, any previous peripheral revascularization (Hazard Ratio [HR] 4.7, 95% CI 3.3-6.8, P<0.01), baseline atrial fibrillation (HR 1.8, 95% CI 1.1-3.2, P=0.03), and baseline ankle-brachial index ≤0.60 (HR 1.3 per 0.10 decrease, 95% CI 1.1-1.5, P<0.01) were associated with higher ALI risk. Older age (HR 0.8 per 10-year increase, 95% CI 0.7-1.0, P=0.02) and baseline statin use (HR 0.7, 95% CI 0.5-0.9, P<0.01) were associated with lower risk for ALI. There was no relationship between randomized treatment to ticagrelor or clopidogrel and ALI. Among patients with previous revascularization, surgical versus endovascular procedures performed more than 6 months prior were associated with ALI (adjusted HR 2.63, 95% CI 1.75-3.96). In the overall population, ALI hospitalization was associated with subsequent MACE (adjusted HR 1.4, 95% CI 1.0-2.1, P=0.04), all-cause mortality (adjusted HR 3.3, 95% CI 2.4-4.6, P<0.01), and major amputation (adjusted HR 34.2, 95% CI 9.7-20.8, P<0.01).Conclusions: Previous peripheral revascularization, baseline atrial fibrillation, and lower ankle-brachial index identify peripheral artery disease patients at heightened risk for ALI, an event associated with subsequent cardiovascular and limb-related morbidity and mortality.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01732822. [ABSTRACT FROM AUTHOR]

First, a detailed analysis of the specific causes of death in all patients enrolled in all PTX-based trials for PAD treatment needs to be performed. Third, all ongoing PTX-based clinical trials need to determine and monitor the cause of mortality and possible link to PTX therapy. [Extracted from the article]

Introduction: The protective relation of high density lipoprotein-cholesterol (HDLC) with coronary heart disease may be weakened in the presence of inflammation; however, whether inflammation may attenuate any association of HDL-C with peripheral arterial disease (PAD) is unknown. Hypothesis: We hypothesized that inflammation measured by high-sensitivity Creactive protein (hs-CRP) will attenuate any inverse association of HDL-C with PAD. Methods: We studied 6512 men and women aged ≥ 40 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999-2004 who had measures of ankle brachial index (positive for PAD defined as <0.9 or ≥1.5), lipids, high-sensitivity CRP (hs-CRP) and other risk factors. Groups were categorized by low (<40 mg/dL for men or <50 mg/dl or women), intermediate (40 or 50-59 mg/dL), and high (≥60 mg/dL) HDL-C, and low (<1 mg/L), normal (1-3), and high (3 mg/L) hs-CRP levels. We evaluated the odds ratio (ORs) for PAD by logistic regression adjusted for age, race, gender, low density lipoproteincholesterol, smoking, diabetes, body mass index, systolic blood pressure waist circumference and triglycerides. Results: Those with the highest hs-CRP levels had the highest prevalence of PAD (8.5-10.8%), regardless of level of HDL-C (figure 1). Using high HDL-C/low hs-CRP as the reference, the likelihood of PAD was significantly increased among those with normal and high hs-CRP within the intermediate HDL-C group: OR 4.7 (95%CI 1.6, 14.1) and OR 4.5 (95% CI 1.4,14.2), respectively. Among those with normal and high hs-CRP within the low HDL-C group, the likelihood of PAD was also increased:OR 5.0 (95% CI 2.1,12,1) and OR 6.4 (95% CI 2.2,18.1), respectively. Conclusion: High hs-CRP is associated with higher likelihood of PAD across all ranges of HDL-C, but especially when HDL-C is normal or low. These results support the value of combined hs-CRP and HDL-C in risk stratification for PAD which should be validated by prospective studies. [ABSTRACT FROM AUTHOR]