Aspirin resistance (AR) and clopidogrel resistance (CR) are terms used to describe a reduction in the medication's efficacy in inhibiting platelet aggregation despite regular dosing. This review ...gives context to the clinical role and implications of antiplatelet resistance in peripheral arterial disease (PAD).
A review of English-language literature on AR and CR in PAD involving human subjects using PubMed and MEDLINE databases was performed in April 2017. A total of 2075 patients in 22 relevant studies were identified. To give this issue context, a review of the larger, more established literature on antiplatelet resistance in coronary disease was undertaken, identifying significant research associating resistance to major adverse cardiovascular events (MACEs).
Studies in the coronary arterial disease literature have strongly associated antiplatelet resistance with increased MACE. Prevalence of AR or CR in coronary disease appears to be >55% for each in some studies. Meta-analyses of >50 studies revealed that AR and CR are significantly associated with MACE (relative risk of 2.09 and 2.8, respectively). This adds further weight to the literature reporting antiplatelet resistance as an independent predictor of and a threefold risk factor for major adverse cardiovascular events. The prevalence of resistance in PAD in this review was comparable to that in the coronary disease literature, with AR and CR prevalence up to 60% and 65%, respectively. There is evidence that the adverse effects of antiplatelet resistance are significant in PAD. In fact, research directly studying stent thrombosis populations with either coronary arterial disease or PAD revealed more significantly impaired platelet responsiveness to clopidogrel and aspirin in PAD compared with similar individuals with coronary disease. AR in PAD was found in studies to be a significant risk factor for iliofemoral stent reocclusion (P = .0093) and stroke in patients with symptomatic carotid disease (P = .018). CR was found to be a significant, independent risk factor in predicting ischemic outcomes in several recent PAD studies (P < .0001). Loss-of-function carriers of enzyme CYP2C19, important in clopidogrel metabolism, have a 30% greater risk of ischemic events (P < .001). Importantly, less antiplatelet drug resistance may be encountered with newer antiplatelet agents, including ticagrelor and prasugrel, because of reduced enzymatic polymorphisms.
The limited research addressing AR and CR in PAD suggests that further research is required to clarify the role of platelet assays and potential for individualized antiplatelet therapy.
Surveillance of cardiovascular Events in Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN (SEASON) is a 2-year, prospective, real-world, registry study conducted in Japan from 2009 ...to 2013. This post hoc analysis evaluated risk factors for limb ischemia in patients with peripheral arterial disease (PAD) and ankle–brachial index (ABI) <0.90. Vascular events were adjudicated by an Efficacy Endpoint Review Committee. Cox regression identified predictors of limb-specific peripheral vascular events (amputation, development of critical limb ischemia, and acute limb ischemia). Patients (n = 6565) were stratified according to ABI: normal (≥1.0; n = 1300), borderline (0.90 ≤ ABI ≤ 1.0; n = 776), and abnormal (<0.90; n = 4489). Compared to normal ABI, patients with ABI <0.90 had a significantly higher risk of any vascular event, all-cause death, and any limb-specific peripheral vascular event. Risk factors for limb-specific vascular events included history of lower extremity revascularization/amputation (adjusted hazard ratio: 2.18; 95% confidence interval CI: 1.49-3.20), chronic kidney disease (2.00; 1.33-3.00), diabetes (1.71; 1.16-2.52), and ABI <0.4 (4.45; 2.62-7.55) or <0.7 (1.78; 1.15-2.76). These findings from a Japanese real-world population confirm the increased vascular risk of patients with PAD and ABI <0.90 and identified risk factors for limb-specific peripheral vascular events.
Peripheral Arterial Disease in Women: The Gender Effect Patel, Toralben; Baydoun, Hassan; Patel, Nimesh K. ...
Cardiovascular revascularization medicine,
March 2020, 2020-03-00, 20200301, Letnik:
21, Številka:
3
Journal Article
Recenzirano
Peripheral arterial disease (PAD) is a common atherosclerotic disease approximately affecting 8.5 million Americans above age 40 and is associated with significant functional impairment, morbidity ...and mortality from both cardiovascular and non-cardiovascular causes. PAD has increasing prevalence in females contrary to previous findings. Compared to men, women with PAD are more asymptomatic or have atypical symptoms. Women with PAD have increased quality of life impairment, increased risk of depression and increased cardiovascular mortality. The intent of this review is to provide an update on gender differences in PAD that can help in timely diagnosis and appropriate management through intensive cardiovascular risk factor modification, exercise program and guideline directed therapy to improve cardiovascular outcomes.
•Peripheral arterial disease (PAD) is a significant healthcare burden affecting 8–10 million Americans.•PAD confers equal morbidity and mortality as well as economic costs to coronary artery disease and stroke.•Significant gender differences exist in epidemiology, clinical assessment, treatment and outcomes for PAD patients.•Women suffer from functional impairment, morbidity and mortality from PAD at higher rates as compared to men.•Timely diagnosis, treatment and cardiovascular risk modification in women will reduce significant morbidity and mortality from cardiovascular as well as non-cardiovascular causes.
Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and ...cardiovascular risk.
Healthy volunteers (n=58, discovery; n=49, validation) were exposed to 4 weeks of ticagrelor with platelet RNA data, platelet function, and self-reported bleeding measured pre-/post-ticagrelor. RNA sequencing was used to discover platelet genes affected by ticagrelor, and a subset of the most informative was summarized into a composite score and tested for validation. This score was further analyzed (1) in CD34+ megakaryocytes exposed to an P2Y12 inhibitor in vitro, (2) with baseline platelet function in healthy controls, (3) in peripheral artery disease patients (n=139) versus patient controls (n=30) without atherosclerosis, and (4) in patients with peripheral artery disease for correlation with atherosclerosis severity and risk of incident major adverse cardiovascular and limb events.
Ticagrelor exposure differentially expressed 3409 platelet transcripts. Of these, 111 were prioritized to calculate a Ticagrelor Exposure Signature score, which ticagrelor reproducibly increased in discovery and validation cohorts. Ticagrelor's effects on platelets transcripts positively correlated with effects of P2Y12 inhibition in primary megakaryocytes. In healthy controls, higher baseline scores correlated with lower baseline platelet function and with minor bleeding while receiving ticagrelor. In patients, lower scores independently associated with both the presence and extent of atherosclerosis and incident ischemic events.
Ticagrelor-responsive platelet transcripts are a biomarker for platelet function and cardiovascular risk and may have clinical utility for selecting patients with optimal risk:benefit for ticagrelor use.
The Global Limb Anatomic Staging System (GLASS) is a new method of quantifying the anatomic severity of infrainguinal disease in patients with chronic limb-threatening ischemia. However, because ...GLASS has undergone limited validation, its value as an aid to shared decision-making regarding the choice of revascularization strategy remains incompletely defined. Here we report the relationship between GLASS and outcomes in a contemporary series comprising all 309 patients who underwent an attempt at femoropopliteal and/or infrapopiteal endovascular therapy for chronic limb-threatening ischemia in our unit between 2009 and 2014.
Baseline patient characteristics and outcome data including immediate technical success (ITS), amputation-free survival (AFS), overall survival, limb salvage, freedom from reintervention (FF-R), and freedom from major adverse limb events (FF-MALE) were obtained from hospital databases. GLASS grades and stage were obtained from pre-endovascular therapy angiographic imaging. Outcome data were censored on May 31, 2017.
Baseline patient characteristics were similar across different GLASS femoropopliteal and IP grades and overall limb stages. Worsening GLASS stage was associated with a significant reduction in ITS (97.5% vs 91.5% vs 84.0%; P = .029). At 72 months FF-R (hazard ratio, 2.00; 95% confidence interval, 1.11-3.57; P = .020) and FF-MALE (hazard ratio, 1.76, 95% confidence interval, 1.10-2.81; P = .019) were significant worse in GLASS stage 3 than in stage 2 limbs.
In our study, there were significant differences in ITS, FF-R and FF-MALE between limbs with GLASS stage 2 and 3 disease. However, further GLASS refinement seems likely to be required if its usefulness in everyday clinical practice as an aid to shared decision-making regarding the choice of revascularization strategy is to be maximized.
To evaluate safety and effectiveness of the iCAST Covered Stent for treatment of iliac artery atherosclerotic lesions.
The iCARUS trial (ClinicalTrials.gov Identifier: NCT00593385) was a single-arm, ...prospective, multicenter study that enrolled 152 per protocol subjects at 25 sites in the United States and Germany. Subjects with multiple lesions and/or stents were eligible. The primary endpoint was the composite rate of death within 30 days, target lesion revascularization (TLR) within 9 months, or restenosis at 9 months after procedure. Secondary endpoints included major adverse vascular events (MAVEs), primary patency, freedom from TLR, and clinical success.
Device and acute procedural success were achieved in 98.7% and 92.7% of cases, respectively. MAVE rate was 4.6% at 30 days. The 9-month primary composite endpoint rate was 8.1% (10/123), which was below the performance goal of 16.57%. Nine-month primary patency, defined as continuous flow without revascularization, bypass, or target limb amputation, was 96.4%. Freedom from TLR at 9 months and 3 years was 97.2% and 86.6%, respectively. Early clinical success was seen in 88.7% of subjects at 30 days with sustained clinical benefit in 72.4% of subjects at 3 years.
The iCARUS study demonstrated that the iCAST Covered Stent was safe and effective for treatment of atherosclerotic iliac artery lesions with sustained clinical benefit out to 3 years.
Abstract Background Low ankle–brachial index (ABI) is associated with increased risk of subsequent cardiovascular disease events, independent of Framingham risk factors, but its ability to improve ...risk prediction prospectively has not been examined. Methods We conducted post-hoc analysis of data from Atherosclerosis Risk in Communities Study (ARIC Study), a large prospective cohort study. 11,594 white and African American (24.2%) men and women, aged 45–64 years, with available Framingham Risk Score (FRS) variables and ABIs at baseline, and without known history of cardiovascular disease or diabetes mellitus or known peripheral arterial disease at baseline were assessed for hard cardiovascular events (hCVD; defined as heart attack, coronary death or stroke) over median follow-up of 10 years. Hazard ratios, C statistic, and net reclassification indexes were calculated to determine the independent predictive ability of ABI compared with FRS. Results 659 hCVD events occurred. Standardized ABI was significantly associated with hCVD events but with a relatively small effect on events (hazard ratios of 0.85 per standard deviation (95% CI 0.79–0.91) ( p -value < 0.0001)). The C statistic of FRS modified with ABI was only modestly improved (0.756–0.758). Net reclassification improvement, an indicator of prospective prediction performance, using an ABI threshold of 0.9 was small and statistically insignificant (0.8%, p = 0.50). Conclusions Although the ABI adjusted for Framingham risk variables was independently associated with subsequent events in terms of hazard ratios, the independent effect of ABI when adjusted for FRS was small in magnitude, and the FRS performed similarly with or without integration or supplementation with ABI. These findings do not provide strong evidence to support FRS modification to include ABI.
Background
Atherosclerosis is a chronic inflammatory process involving the immune system and formation of reactive oxygen species (ROS). We investigated changes of mononuclear blood cells and ROS ...production in relation to the walking distance of patients with intermittent claudication during home-based exercise training.
Methods
Forty patients with intermittent claudication were asked to perform a home-based exercise training for a mean time of 12 months. ROS formation was measured using the luminol analogue L-012. Peripheral blood leucocytes monocytes, polymorphonuclear neutrophils (PMN) and dendritic cells (DC) were analysed by flow cytometry and analysed for the expression of major inflammatory surface molecules.
Results
At follow-up, patients showed an increased walking distance and reduced ROS production upon stimulation with a phorbol ester derivative (PDBu) (
p
< 0.01). Monocytes changed their inflammatory phenotype towards an increased anti-inflammatory CD14
++
CD16
−
subpopulation (
p
< 0.0001). Adhesion molecules CD11b, CD11c and TREM-1 on monocytes and PMN decreased (all
p
< 0.01). On DC expression of HLA-DR, CD86 or CD40 decreased at follow-up. Inflammatory markers like fibrinogen, C-reactive protein or soluble TREM-1 (sTREM-1) decreased over the observation period. Finally, we found a close relation of sTREM-1 with the walking distance, fibrinogen and ROS production.
Conclusions
We observed an amelioration of the proinflammatory phenotype on monocytes, DC and PMN, as well as a reduced ROS production in PAD patients under home-based exercise, paralleled by an increased walking distance. Our data suggest that a reduced inflammatory state might be achieved by regular walking exercise, possibly in a dimension proportionately to changes in walking distance.
Local drug delivery of an anti-proliferative drug from balloon catheter systems to the site of arterial injury has been attempted repeatedly over the years with limited success in drug uptake and ...retention. Accessibility of the drug at the site is critical to combat the body's response to the procedural trauma of angioplasty. Recently, formulations have been designed which achieve delivery of therapeutic doses of the anti-proliferative drug paclitaxel to arteries with higher efficiency and longer tissue retention. These formulations succeed through formation of a drug reservoir in the artery wall enabling release after the initial angioplasty procedure. These formulations have become the cornerstone of several drug coated balloon (DCB) technologies which have found an initial, broad therapeutic application in the treatment of stenosis of the superficial femoral artery (SFA). DCBs achieve drug delivery while leaving no implant behind and represent a new class of combination products developed at the interface of engineering, chemistry and medical science. This review article summarizes the development of the LUTONIX® drug coated balloon catheter. The introduction of DCB technology has provided clinicians and patients with new SFA treatment options while ongoing clinical evidence in additional vascular beds is generated.
Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European ...Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin-based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2 × 2.5 mg) is also indicated to prevent cardiovascular events. Dual antiplatelet therapy (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD.
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