Risultati per: Arteriopatia Periferica: in chi sospettare una PAD

Circulation, Volume 148, Issue Suppl_1, Page A16776-A16776, November 6, 2023. Introduction:Peripheral artery disease (PAD) and chronic kidney disease (CKD) are common comorbidities in patients with heart failure (HF). Importantly, CKD is associated with a greater risk of incident PAD and is a known risk factor for worse outcomes in HF patients. However, it is unclear whether the concomitant existence of PAD and CKD increases the risk of recurrent hospitalization for acute decompensated heart failure (ADHF).Methods:Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted hospital surveillance of ADHF with events verified by physician review. Demographics, comorbidities, laboratory data, and medications were abstracted from medical record by trained personnel. Hazard ratios of ADHF readmissions were analyzed using repeat-events Cox regression. Models were adjusted for age, race, sex, year and hospital of admission, coronary artery disease (CAD), COPD, and diabetes mellitus. CKD was defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73m2.Results:From 2005-2018, there were 1049 index hospitalizations for ADHF (mean age 77 years, 66% white) with measured creatinine, who were discharged alive. Of these, 155 (15%) had a diagnosis of PAD and 66% had CKD stage 3a or worse (GFR ≤60 mL/min/1.73m2). Patients with PAD had a greater prevalence of smoking, CAD, myocardial infarction, and stroke. The 1-year ADHF readmission rate tended to be higher in patients with PAD, irrespective of CKD stage, compared to those without PAD (Figure 1). After adjustments, PAD was associated with greater hazards of 1-year ADHF readmissions, both in patients with CKD stage 3a or worse (HR, 1.71; 95% CI: 1.25 – 2.32) and without CKD (HR, 1.84; 95% CI: 1.07-3.15).Conclusion:Patients with ADHF and concomitant PAD have a higher prevalence of cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of the CKD status. Focused strategies to prevent ADHF readmission in this high-risk group are warranted.

Circulation, Volume 148, Issue Suppl_1, Page A14010-A14010, November 6, 2023. Background:Cardiovascular benefits of 2.5 mg twice daily rivaroxaban plus aspirin therapy (RIV+ASA) has been demonstrated in patients with arterial diseases.Hypothesis:RIV+ASA is associated with reduced platelet activation and plasma inflammation and coagulation activation markers in patients with CAD and/or PAD who were on ASA.Methods:In this open-label biomarker study, patients on 81 mg/day ASA were randomized to continue ASA or RIV+ASA for 12 weeks. We assessed ADP-, α-thrombin-, and tissue factor-induced platelet aggregation (PA) using conventional aggregometry, platelet-fibrin clot strength (PFCS) by INTEM (intrinsic pathway activator) and EXTEM (extrinsic pathway activator) using thromboelastometry, shear-induced PA by platelet function analyzer-100, D-dimer and fibrinogen using coagulation analyzer, hs-CRP and interleukin-6 using ELISA method at baseline, and four weeks and 12 weeks post-randomization.Results:Data was available in 9 patients with RIV + ASA and ten patients with ASA-only therapy. Most patients were male, Caucasians, obese and older. There were no differences in baseline demographics, medications, and laboratory values between groups, except patients in RIV + ASA group had higher white blood cell counts (p=0.028) and lower baseline 2uM ADP-induced PA (p=0.03). There were no differences in other laboratory measurements between baseline and post-randomization time points within the group or at 4- and 12-week time points between groups, except D-dimer values were significantly lower at 12 weeks (p=0.038) in the RIV + ASA vs. ASA-only group. No significant adverse events were observed.Conclusions:Twelve weeks of rivaroxaban plus aspirin vs. aspirin was associated with similar levels of platelet aggregation, platelet fibrin clot strength, fibrinogen and inflammation markers, and lower d-dimer levels.

Circulation, Ahead of Print. 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 to 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];Pinteraction=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.

Annals of Internal Medicine, Volume 176, Issue 9, Page JC99, September 2023.

Annals of Internal Medicine, Ahead of Print.

Introduction
Peripheral arterial disease (PAD) is a key risk factor for cardiovascular disease, foot ulceration and lower limb amputation in people with diabetes. Early diagnosis of PAD can enable optimisation of therapies to manage these risks. Its diagnosis is fundamental, though challenging in the context of diabetes. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most accurate in routine clinical practice.
The aim of this study is to determine the diagnostic performance of a variety of tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of PAD in people with diabetes as determined by a reference test (CT angiography (CTA) or magnetic resonance angiography (MRA)). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan).

Methods and analysis
A prospective multicentre diagnostic accuracy study (ClinicalTrials.gov Identifier NCT05009602). We aim to recruit 730 people with diabetes from 18 centres across the UK, covering primary and secondary healthcare. Consenting participants will undergo the tests under investigation. Reference tests (CTA or MRA) will be performed within 6 weeks of the index tests. Imaging will be reported by blinded consultant radiologists at a core imaging lab, using a validated scoring system, which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ≥50% stenosis, or tandem lesions with a combined value of ≥50%, will be used as the threshold for the diagnosis of PAD. The primary outcome measure of diagnostic performance will be test sensitivity.

Ethics and dissemination
The study has received approval from the National Research Ethics Service (NRES) (REC reference 21/PR/1221). Results will be disseminated through research presentations and papers.

Trial registration number
NCT05009602.

Circulation, Volume 146, Issue Suppl_1, Page A12197-A12197, November 8, 2022. Background:In trials of patients with coronary artery disease (CAD), unknown deaths (e.g. out of hospital) are often categorized as sudden/presumed cardiovascular (CV) based on observations that recurrent coronary events are a major cause of mortality. Such conventions are applied broadly to CV trials, including those in peripheral artery disease (PAD). Recent trials in patients selected on the basis symptomatic PAD, such as EUCLID trial, report that only ~1/3 have known CAD. Therefore, understanding the causes of death in patients in trials of symptomatic PAD may help elucidate whether different conventions should be considered.Hypothesis and Methods:VOYAGER PAD enrolled patients with symptomatic PAD after lower extremity revascularization. Source documents were collected for all deaths and cause was adjudicated by an independent blinded CEC using accepted CV trial conventions for those dying out of hospital. For this post-hoc analysis, source documents were re-reviewed to provide further details regarding specific causes of deaths.Results:6564 patients were randomized and followed for a median of 28 months. A total of 637 deaths occurred, and of these, 35% were CV, 22% were unknown (e.g. out of hospital, sudden deaths), and 43% were non-CV. Of the CV deaths, 40% (14% of all deaths) were atherothrombotic (e.g. acute MI, stroke, PE), while 60% (21% of all deaths) were not atherothrombotic (e.g. heart failure, shock). Deaths due to cancer (17%) and infection (15%) were more frequent than atherothrombotic deaths.Conclusions:Patients recruited into trials for symptomatic PAD die of diverse causes. Atherothrombosis caused a minority of deaths, while heart failure, cancer, and infection are as or more frequent. These observations suggest that causes of death differ in populations selected on the basis of PAD versus CAD and that assumptions underlying categorization of deaths of unknown etiology should be carefully considered in these distinct populations.

Circulation, Volume 146, Issue Suppl_1, Page A10240-A10240, November 8, 2022. Introduction:Blood pressure (BP) trials have established optimal targets for major adverse cardiovascular event (MACE) prevention; however, less intensive BP control (also called permissive hypertension) is sometimes utilized to minimize end organ damage in specific settings such as acute stroke and acute kidney injury. An analysis from ALLHAT found that systolic blood pressure (SBP)

Circulation, Volume 146, Issue Suppl_1, Page A10889-A10889, November 8, 2022. Introduction:Patients with critical limb ischemia (CLI) have a class I indication for lower extremity revascularization (LER) by either endovascular or surgical approach. A common complication is recurrent arterial occlusion requiring unplanned index limb revascularization (UILR). VOYAGER PAD established the efficacy of rivaroxaban in patients with symptomatic peripheral artery disease (PAD) after successful LER, including a reduction in UILR. Whether this benefit differs by LER approach for CLI is unknown.Hypothesis:Rivaroxaban reduces UILR regardless of LER approach for CLI.Methods:LER indication (CLI or claudication) and approach were captured at baseline. The primary composite endpoint was acute limb ischemia, major vascular amputation, MI, ischemic stroke or CV death. TIMI major bleeding was the primary safety outcome. UILR was a prespecified secondary outcome. A Cox proportional-hazards model was used to calculate hazard rations and 95% confidence intervals.Results:Among 6,564 participants randomized,1,533 (23%) had CLI, of whom 696 (45%) and 837 (55%) underwent surgical and endovascular LER, respectively. CLI patients on rivaroxaban had fewer events at three years compared to those on placebo (HR 0.85). Efficacy of rivaroxaban for the primary endpoint (p-interaction 0.40) and safety (p-interaction 0.18) in CLI were consistent regardless of approach. On background therapy (aspirin in all, statins ~80%, DAPT ~50%), at a median of 28 months, UILR occurred in 26.2% and 14.3% after endovascular and surgical LER, respectively. Rivaroxaban significantly reduced UILR by 22% in patients with CLI (HR 0.78, p=0.019, Figure), with consistent benefits in those treated with endovascular and surgical LER (p-interaction 0.70).Conclusions:CLI patients have high rates of UILR after LER. Rivaroxaban reduced the rate of UILR in this population, regardless of endovascular or surgical approach.

Circulation, Volume 146, Issue Suppl_1, Page A9928-A9928, November 8, 2022. Introduction:Amputation is a severe consequence of peripheral artery disease (PAD), and systems for risk stratification have been developed. The performance of these systems in trials of PAD patients after successful lower extremity revascularization (LER) and receiving modern medical therapies has not been well described.Hypothesis:Risk of amputation is associated with the Rutherford Chronic Limb Ischemia class as well as the wound, ischemia, and foot infection (WIfI) grade in patients with PAD after LER.Methods:Patients in the VOYAGER PAD trial were assigned a Rutherford class at baseline and follow up. A WIfI score was assigned by 2 vascular specialists blinded to outcome and treatment allocation. Incidence of the composite of first major or minor amputation through 3 years were calculated by risk group.Results:Of 6,564 randomized, Rutherford was available in 6543 and WIfI in 6471. Due to the trial’s inclusion criteria, no Rutherford 6/WIfI high risk were included. Despite successful LER, there was a stepwise increase in the risk of amputation (p

Circulation, Volume 146, Issue Suppl_1, Page A15616-A15616, November 8, 2022. Introduction:Peripheral artery disease (PAD) affects >8 million people nationwide and is disabling. PAD-associated myopathy causes weakness yet is understudied. Unbiased transcriptomic profiling of muscle satellite cells (MuSC) which drive recovery may elucidate the etiology of ischemic myopathic change.Hypothesis:MuSC in PAD differentially express injury associated pathways that may be novel targets for intervention to reduce ischemic myopathy.Methods:Muscle tissue biopsies were obtained during lower extremity amputation or bypass in PAD/ischemic (N=4; ABI

Circulation, Volume 146, Issue 14, Page 1103-1104, October 4, 2022.