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This study aimed to elucidate the prognostic influence of statins in relation to the degree of inflammation at the time of endovascular therapy (EVT) for patients with peripheral artery disease (PAD). This observational study included patients with PAD who underwent EVT, including 285 statin users and 275 statin non-users. They were assigned into four groups depending on C-reactive protein (CRP) level at the time of EVT: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1-0.3 mg/dL), intermediate-high CRP (0.3-1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category. Overall, statin users showed a lower event rate than non-users (log-rank, p=0.02). However, the event rates did not differ significantly between statin users and non-users in the low, intermediate-low, and intermediate-high CRP categories. In the high CRP category, statin users showed a lower event rate than non-users (p=0.002). In this population, multivariate Cox regression analysis revealed that statin use was independently associated with the primary endpoint (hazard ratio: 0.28 [95% confidence interval: 0.14-0.55]). Statins may exert favorable prognostic effects in PAD patients with highly elevated CRP levels, but not in those with low-to-moderate CRP levels., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Peripheral artery disease (PAD) remains a major cause of morbidity and future cardiovascular events despite advancement in the surgical interventions and optimal medical therapy. The aim of our study is to evaluate the efficacy and safety of anticoagulation (AC) therapy for reducing cardiovascular and limb events in patients with PAD. PUBMED, Medline, and Cochrane Library were searched through 2020 for randomized clinical trials comparing major adverse cardiovascular events (MACE) and risk of major bleeding (MB), between AC and standard of care (SOC) therapy, among patients with PAD. Meta-analysis was performed using weighted pooled absolute risk difference (RD) with 95% confidence interval (CI) and fixed effects model for overall and sub-groups of full dose (FD) and low dose (LD) AC therapies. Amongst 17,684 patients from 7 different studies, the addition of AC to SOC therapy was associated with MACE reduction (RD -0.022, 95% CI -0.033 to -0.012, p <0.001) and increased MB (RD 0.02, 95% CI 0.014 to 0.025, p <0.001). For FD, MACE reduction was (RD -0.021, 95% CI -0.042 to 0.001, p = 0.061) and MB (RD 0.036, 95% CI 0.025 to 0.047, p <0.001). For LD, MACE reduction was (RD -0.023, 95% CI -0.035 to -0.011, p <0.001) and MB (RD 0.011, 95% CI 0.005 to 0.017, p <0.001). In conclusion, addition of AC to the current SOC therapy can mitigate future MACE events in patients with PAD albeit at risk of increased bleeding. LD AC is associated with an efficacy/safety net benefit compared to FD AC therapy., (Copyright © 2021. Published by Elsevier Inc.)

Peripheral arterial disease (PAD) is an atherosclerotic process involving both modifiable and nonmodifiable risk factors. Prospective cohort studies show that patients with PAD have a 6-fold greater risk of death from cardiovascular disease than those without PAD. Currently, there is no effective treatment for PAD. The study was a randomized, placebo-controlled trial, involving 180 patients, aged 35 to 75. The subjects were divided into 2 groups. One group underwent 24 weeks of nutraceutical treatment consisting in the administration of 4 capsules of Annurca apple polyphenolic extract (AMS)/day. The placebo group was administered with identically appearing capsules containing only maltodextrin. Primary outcome measures were: walking autonomy, ankle-brachial index, acceleration time. In the AMS group, at the end of the treatment period, walking autonomy was increased on average by 69% (p <0.05), while slighter effects were registered as regards ankle-brachial index (+25%; p <0.05) and acceleration time (-3.6%; p <0.05), when compared with baseline. Placebo group revealed no significant differences as regards variations of all outcomes measures (p >0.05). Our preliminary results may indicate AMS product as a promising natural and safe tool for treatment of symptoms related to PAD., (Copyright © 2018. Published by Elsevier Inc.)

Patients with previous atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) are at high risk of future cardiovascular events. Despite maximally tolerated doses of statins, many patients still have elevated low-density lipoprotein cholesterol (LDL-C) levels. We evaluated the efficacy and safety of alirocumab in patients with ASCVD and/or HeFH on a maximally tolerated dose of statin (rosuvastatin 20 or 40 mg, atorvastatin 40 or 80 mg, or simvastatin 80 mg, or lower doses with an investigator-approved reason) ± other lipid-lowering therapies from 5 placebo-controlled phase 3 trials (52 to 78 weeks). Patients with (n = 2,449) and without (n = 1,050) ASCVD were pooled from the FH I, FH II, HIGH FH, LONG TERM, and COMBO I trials. Patients with HeFH with (n = 575) and without ASCVD (n = 682) were pooled from all trials except COMBO I. High-intensity statins were utilized in 55.7% to 59.0% and in 72.4% to 87.6% of the ASCVD and the HeFH groups, respectively. Efficacy end points included LDL-C percent change from baseline to week 24 stratified by alirocumab dose. Mean baseline demographics and lipid levels were comparable in alirocumab- and placebo-treated patients. LDL-C reductions from baseline at week 24 ranged from 46.6% to 51.3% for alirocumab 75/150 mg and from 54.1% to 61.9% for alirocumab 150 mg in ASCVD and HeFH groups and were sustained for up to 78 weeks. LDL-C reductions with alirocumab were independent of ASCVD and/or HeFH status (interaction p value >0.05). Concordant results were observed for other lipids analyzed. The overall safety in the subgroups analyzed was similar in both treatment arms. Injection-site reactions were observed more frequently with alirocumab versus placebo., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

There are limited contemporary data on guideline-directed medical therapy (GDMT) utilization and long-term clinical outcomes in patients with peripheral artery disease (PAD) with and without concomitant coronary artery disease (CAD). From 2006 to 2013, 879 patients with claudication or critical limb ischemia (CLI) underwent diagnostic angiography or therapeutic endovascular intervention at our multidisciplinary vascular center. GDMT use was assessed at the time of angiography, and major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality were determined during 5 years of follow-up. Cox proportional hazard modeling was used to adjust for baseline differences between patients with and without concomitant CAD. Despite a higher adherence to GDMT (all p ≤0.002) for the use of aspirin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and statins, patients with PAD and concomitant CAD had higher unadjusted 5-year rates of MACCE (hazard ratio [HR] 1.7, 95% CI 1.3 to 2.1, p = 0.0001) and all-cause mortality (HR 1.86, 95% CI 1.4 to 2.4, p = 0.0001). After adjustment for baseline co-morbidities, the presence of CAD remained an independent risk factor for mortality (adjusted HR 1.35, 95% CI 1.02 to 1.80, p = 0.04) but not for MACCE (adjusted HR 1.24, 95% CI 0.96 to 1.60, p = 0.10) in patients with PAD. A sensitivity analysis limited to patients with CLI demonstrated that concomitant CAD was associated with significantly higher adjusted rates of both MACCE (adjusted HR 1.52, 95% CI 1.14 to 2.03, p = 0.01) and mortality (adjusted HR 1.64, 95% CI 1.12 to 2.20, p = 0.006). In conclusion, despite higher rates of GDMT use, PAD patients with concomitant CAD had significantly increased risk of all-cause mortality during a 5-year postprocedural follow-up. The subgroup of CLI patients with concomitant CAD was at particularly high risk for both MACCE and all-cause mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is a systemic process involving multiple vascular beds and includes coronary heart disease (CHD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD). All these manifestations are associated with an increased risk of subsequent myocardial infarction, stroke, and death. Guideline-directed medical therapy is recommended for all patients with CVD. In a cohort of US veterans, we identified 1,242,015 patients with CVD receiving care in 130 Veterans Affairs facilities from October 1, 2013 to September 30, 2014. CVD included diagnoses of CHD, PAD, or ICVD. We assessed the frequency of risk factor optimization and the use of guideline-directed medical therapy in patients with CHD, PAD alone, ICVD alone, and PAD + ICVD groups. A composite of 4 measures (blood pressure <140/90 mm Hg, A1c <7% in diabetics, statin use, and antiplatelet use in eligible patients), termed optimal medical therapy (OMT) was compared among groups. Multivariate logistic regression was performed with CHD as the referent category. CHD comprised 989,380 (79.7%), PAD alone 70,404 (5.7%), ICVD alone 163,730 (13.2%), and PAD + ICVD 18,501 (1.5%) of the cohort. Overall, only 36% received OMT with adjusted odds ratios of 0.54 (95% CI 0.53 to 0.55), 0.77 (0.76 to 0.78), and 0.97 (0.94 to 1.00) for patients with PAD alone, ICVD alone, and PAD + ICVD, respectively, compared with patients with CHD. In conclusion, OMT was low in all groups. Patients with PAD alone and ICVD alone were less likely to receive OMT than those with CHD and PAD + ICVD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction <40%, on warfarin response has not been evaluated. Here, we assess the influence of LVSD on warfarin dose, anticoagulation control (percent time in target range), and risk of over-anticoagulation (international normalized ratio >4) and major hemorrhage. Of the 1,354 patients included in this prospective cohort study, 214 patients (16%) had LVSD. Patients with LVSD required 11% lower warfarin dose compared with those without LVSD (p <0.001) using multivariate linear regression analyses. Using multivariate Cox proportional hazards model, patients with LVSD experienced similar levels of anticoagulation control (percent time in target range: 51% vs 53% p = 0.15), risk of over-anticoagulation (international normalized ratio >4; hazard ratio 1.01, 95% confidence interval 0.82 to 1.25; p = 0.91), and risk of major hemorrhage (hazard ratio 1.11; 95% confidence interval 0.70 to 1.74; p = 0.66). Addition of LVSD variable in the model increased the variability explained from 35% to 36% for warfarin dose prediction. In conclusion, our results demonstrate that patients with LVSD require lower doses of warfarin. Whether warfarin dosing algorithms incorporating LVSD in determining initial doses improves outcomes needs to be evaluated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Peripheral arterial disease (PAD), similar to coronary artery disease (CAD), is a significant predictor of cardiovascular morbidity and mortality. Guidelines recommend a low-density lipoprotein (LDL) goal of <100 mg/dl for both groups. We assessed whether lipid control and statin use were as aggressively applied to PAD as to patients with CAD. This retrospective study of patients with the diagnosis of CAD, PAD, or both CAD and PAD compared lipid levels and statin use. For comparison of statins, we used a statin potency unit (1 potency unit=10 mg of simvastatin). Among 11,134 subjects (CAD 9,563, PAD 596, and both CAD and PAD 975), mean LDL in the PAD group was higher than the CAD (92 vs 83 mg/dl, respectively, p<0.001) and the combined CAD and PAD groups (92 vs 80 mg/dl, respectively, p<0.001). Fewer patients with PAD achieved a target LDL of <100 mg/dl compared with CAD (62% vs 78%, respectively, p<0.001) and the combined group (62% vs 79%, respectively, p<0.001). Similar differences were noted for a target LDL of <70 mg/dl. Compared with the CAD group, a lesser number of patients with PAD received statin therapy (76% vs 100%, respectively, p<0.001) with lower mean potency unit (5.3 vs 8.1, respectively, p<0.001). In conclusion, our study demonstrated lower use and less aggressive application of statins in patients with PAD compared with patients with CAD, ensuing lower mean LDL in the CAD and combined PAD and CAD groups. Our study suggests that physicians are more aggressive with lipid control in patients with CAD compared with patients with PAD alone., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Peripheral arterial disease (PAD) is a strong risk factor for cardiovascular morbidity and mortality. Therefore, target low-density lipoprotein (LDL) cholesterol level in patients with PAD is ≤70 mg/dl, similar to patients with coronary artery disease (CAD). However, despite their high cardiovascular risk, patients with PAD less frequently achieve LDL cholesterol goals compared to patients with CAD. We aimed to compare LDL cholesterol control in patients after first coronary or peripheral vascular intervention. Included were patients ≥18 years of age without a history of cardiovascular disease who underwent first coronary or peripheral vascular intervention from 2004 through 2010. Primary end points were percentage of patients who achieved the LDL cholesterol goal of <100 and <70 mg/dl. Of 9,138 patients available for analysis, 7,512 (82.2%) underwent first coronary revascularization and 1,626 (17.8%) underwent first peripheral revascularization. Patients after first coronary revascularization were treated more frequently with any statin and with highly potent statins. Furthermore, they more frequently achieved the LDL cholesterol goals compared to patients after first peripheral intervention. This was true for the LDL cholesterol goal of <100 mg/dl (65% and 46.7%, p <0.0001) and for the lower LDL cholesterol goal of <70 mg/dl (23.3% and 13.3%, p <0.0001). Differences in LDL cholesterol control between the 2 groups remained statistically significant after multivariate adjustment. In conclusion, lipid control in patients with PAD is poor and significantly inferior to that of patients with CAD even after the first vascular intervention., (Copyright © 2012 Elsevier Inc. All rights reserved.)