Fibromuscular Disease Research Articles

Outcomes of Direct Oral Anticoagulants with Aspirin Versus Warfarin with Aspirin for Atrial Fibrillation and/or Venous Thromboembolic Disease

▪IntroductionThe direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are increasingly utilized for the management of venous thromboembolic disease (VTE) and/or non-valvular atrial fibrillation (NVAF). Adding aspirin (ASA) to warfarin or DOAC therapy increases bleeding risk. Patients on combination therapy with ASA and an anticoagulant were not well represented in clinical trials comparing DOACs to warfarin. We sought to compare bleeding and thrombotic outcomes with DOACs and ASA compared to warfarin and ASA in a non-trial setting.MethodsWe conducted a retrospective registry-based cohort study of adults on DOAC or warfarin therapy for VTE and/or NVAF. Warfarin treated patients were followed by six anticoagulation clinics. Four out of the six clinics contributed data on their patients that were on DOACs in the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) from January 2009 to June 2021. Patients were excluded if they had a history of heart valve replacement, recent myocardial infarction, or less than 3 months of follow-up. Two propensity matched cohorts (warfarin+ASA vs DOAC+ASA) of patients were analyzed based on ASA use at the time of study enrollment. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression.ResultsWe identified a total of 1,139 patients on DOACs plus ASA and 4,422 patients on warfarin plus ASA. After propensity matching, we compared two groups of 1,114 matched patients. DOAC treated patients were predominately on apixaban (62.3%) and rivaroxaban (30.4%), most often at therapeutic doses (Table 1). Patients were largely (90.5%) on low dose ASA (≤ 100 mg). Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for a median of 11.7 months (interquartile range 4.4 and 34 months). Patients treated with DOAC+ASA had 2.4 thrombotic events per 100 patient years compared to 2.2 thrombotic events per 100 patient years with warfarin+ASA (P=0.78). There were no significant differences observed between groups by thrombotic subtype (stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, table 1). Bleeding was also similar with 30.1 bleeding events per 100 patient years with DOAC+ASA compared to 27.8 bleeds per 100 patient years with warfarin+ASA (P=0.24). There were no significant differences by bleeding subtype (table 1). Hospitalizations for clotting occurred less frequently with DOAC+ASA (0.9 hospitalizations per 100 patient years) compared to warfarin+ASA (1.7 hospitalizations per 100 patient years, P=0.03). Mortality, transfusions, and healthcare utilization were otherwise similar between the two groups.ConclusionsFor patients on a DOAC versus warfarin with ASA for atrial fibrillation and/or venous thromboembolic disease without a recent myocardial infarction or heart valve replacement, bleeding and thrombotic outcomes were similar. [Display omitted] DisclosuresKaatz: Gilead: Consultancy; CSL Behring: Consultancy; Novartis: Consultancy; Bristol Myer Squibb: Consultancy, Research Funding; Pfizer: Consultancy; Alexion: Consultancy; Janssen: Consultancy, Research Funding; Osmosis Research: Research Funding. Kline-Rogers: Janssen: Consultancy; American College of Physicians: Consultancy. Sood: Bayer: Consultancy. Froehlich: Merck: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Boehringer-Ingelheim: Consultancy; Pfizer: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; Fibromuscular Disease Society of America: Research Funding. Barnes: National Certification Board of Anticoagulation Providers: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Acelis: Consultancy; AMAG Pharmaceuticals: Consultancy; Connected Health: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; AC Forum: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy.

The Impact of Adding Aspirin to Warfarin without an Apparent Indication: An Exploration of Patients Anticoagulated for Atrial Fibrillation or Venous Thromboembolic Disease

▪Introduction: Warfarin and aspirin (ASA) are widely used to prevent or treat thromboembolic and atherosclerotic diseases. The most common indications for warfarin use are stroke prevention in atrial fibrillation (AF) and for the treatment of venous thromboembolic disease (VTE). When patients are started on warfarin, many are already taking ASA or they are subsequently placed on ASA due to other co-morbidities. There are limited indications for the combination of warfarin plus ASA, including mechanical heart valves, after percutaneous coronary intervention (PCI), or after acute coronary syndromes. Evidence suggests combination warfarin-ASA may offer no benefit, but place patients at increased bleeding risk outside of these indications.We sought to assess the patient characteristics and outcomes of patients on warfarin for AF or VTE, comparing those who were on concurrent ASA without a strong indication (myocardial infarction [MI] within 6 months, mechanical heart valve or PCI) to those not on ASA. We hypothesized that combination therapy (warfarin-ASA) would result in increased bleeding rates with similar rates of MI, recurrent VTE, stroke, or death.Methods: We conducted a retrospective cohort study of adult patients, initiated on warfarin for AF or VTE between January 2009 and June 2017. Patients were recruited through the Michigan Anticoagulation Quality Improvement Initiative, a collaborative of six outpatient anticoagulation clinics throughout the state of Michigan. Patients with less than three months of follow-up, a MI within six months, and/or history of valve replacement were excluded. Patients were analyzed based on their aspirin use at the time of study enrollment. A HAS-BLED score, modified to exclude aspirin use, and a Charlson Co-morbidity Index was calculated for each patient at enrollment.Analyses were performed using Student's t-tests, Wilcoxon Rank-sum tests, chi-square tests and Fisher's exact tests when appropriate. Survival and Poisson regression analyses were used to evaluate the effect of ASA use on various outcomes.Results: A total of 6,572 patients met the inclusion criteria, with a mean duration of follow-up of 21.2 months; 38% were on warfarin-ASA compared to 62% on warfarin monotherapy. Patients on warfarin-ASA were older (mean 70.2±12.7 vs. 63.7±16.5, p<0.001), more often male (56.7% vs. 47.3%, p<0.001), and were more likely anticoagulated for AF (66.3% vs. 42.3%, p<0.001). Warfarin-ASA patients were more likely to have cardiovascular risk factors (diabetes mellitus, tobacco use, or hypertension), a history of stroke, heart failure, or a history of coronary artery disease (CAD). Patients on warfarin-ASA had a higher HAS-BLED score (mean 2.4±1.2 vs. 1.8±1.2, p<0.001), and Charlson Co-morbidity Index (mean 4.8±2.0 vs. 3.6±2.1, p<0.001).Patients treated with warfarin-ASA vs. warfarin alone experienced less DVTs (0.7/100 patient years [pt-yr] vs. 1.3/100-pt-yr, p=0.002) and PE (0.1/100-pt-yr vs. 0.4/100-pt-yr, p=0.002), but had a higher rate of ischemic/embolic strokes (0.7/100-pt-yr vs. 0.4/100-pt-yr, p=0.02). Emergency department visits and hospitalizations for thromboembolic events were similar. Patients treated with warfarin-ASA vs. warfarin alone had a higher 1-year probability of having a major bleeding event (6.1% vs. 3.2%, p<0.001) or non-major bleeding event (22.9% vs. 18.7%, p=0.004). Warfarin-ASA treated patients had a higher rate of hospitalizations for bleeding (8.4/100-pt-yr vs. 5.7/100-pt-yr, p<0.001), blood transfusions (5.2/100-pt-yr vs. 4.1/100-pt-yr, p=0.009) and all-cause mortality relative to warfarin alone (4.1/100-pt-yr vs. 3.1/100-pt-yr, p=0.005). Kaplan-Meier curves for any clotting event, all bleeding events, major bleeding events, and death are shown (figure 1). A sensitivity analysis was performed that further excluded any history of MI, CAD, PCI, peripheral arterial disease, or coronary artery bypass grafting, and showed similar results.Conclusion: Over one-third of patients in an unselected practice-based setting are treated with warfarin-ASA for AF and/or VTE without a clear indication. Compared to warfarin monotherapy, this was associated with minimally increased protection against VTE but with a significant increase in bleeding and perhaps mortality. Further research is needed to better stratify who should receive aspirin while on warfarin. [Display omitted] DisclosuresSood:Bayer: Research Funding. Kline-Rogers:Janssen: Consultancy; ACP: Consultancy; AC Forum: Membership on an entity's Board of Directors or advisory committees. Almany:Trice Orthopedics: Consultancy; Micardia: Consultancy; Ablative Solutions: Equity Ownership; Kona: Consultancy; Biostar Ventures: Equity Ownership; Boston Scientific Watchman: Research Funding; Abbott Absorb Trial: Research Funding. Kaatz:Daiichi Sankyo: Consultancy, Honoraria; CSL Behring: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Portola: Consultancy. Froehlich:Merck: Consultancy; Fibromuscular Disease Society of America: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Novartis: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees. Barnes:Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Aralez: Consultancy.

Renal artery stenosis: the challenging in diagnosis and therapy

Hypertension is still the most prevalent non-communicable diseases in Indonesia. Renovascular hypertension is one type of secondary hypertension. It is commonly caused by the presence of renal artery stenosis (RAS). Whereas, atherosclerosis (ARAS) and fibromuscular disease (FMD) are the most common causes of RAS. Early diagnosis is necessary because it has the potential to be cured by eliminating stenosis of the renal artery. However, the signs and symptoms of renovascular hypertension are not specific. The supporting examination to diagnose RAS is also expensive. So, screening in the population at risk is needed. The examinations to prove the presence of RAS are arteriography, captopril renogram, renal ultrasonography, renal Doppler ultrasonography, magnetic resonance angiography (MRA), and computed angiographic tomography (CTA).&#x0D; Until now, three therapeutic modalities can be selected in the management of renovascular hypertension; pharmacological therapy, surgical intervention, percutaneous intervention angioplasty with and without stenting. This narrative review summarizes the literature focused on the diagnosis and therapy of RAS.

Renal Artery Stenosis: The Challenging in Diagnosis and Therapy

Hypertension is still the most prevalent of non-communicable diseases in Indonesia. Renovascular hypertension is one type of secondary hypertension. It is commonly caused by the presence of renal artery stenosis (RAS). Whereas, atherosclerosis (ARAS) and fibromuscular disease (FMD) are the most common causes of RAS. Early diagnosis is necessary because it has the potential to be cured by eliminating stenosis of the renal artery. However, the signs and symptoms of renovascular hypertension are not specific. The supporting examination to diagnose RAS is also expensive. So, screening in the population at risk is needed. The examinations to prove the presence of RAS are arteriography, captopril renogram, renal ultrasonography, renal Doppler ultrasonography, magnetic resonance angiography (MRA), and computed angiographic tomography (CTA). Until now, three therapeutic modalities can be selected in the management of renovascular hypertension; pharmacological therapy, surgical intervention, percutaneous intervention angioplasty with and without stenting. This narrative review summarizes the literature focused on the diagnosis and therapy of RAS.

E-Selectin Antagonist GMI-1271 Shows a Favorable Safety, PK and Bleeding Profile in Phase I Studies of Healthy Volunteers

Background: Selectins, among other adhesion-mediated functions, facilitate and augment thrombosis; standard anticoagulants address thrombosis but also increase bleeding risk. Previous work in animal models showed inhibiting E-selectin decreases venous thrombosis (VTE) and vein wall inflammation without adverse bleeding events, making E-selectin inhibition a favorable therapeutic candidate for VTE. GMI-1271 is a potent, specific E-selectin antagonist. Here we report final analysis of safety, PK, biomarker and bleeding risk profile for GMI-1271 in 2 phase 1 studies of healthy subjects.Methods: The first study was a blinded single ascending dose (SAD) evaluation of 2, 5, 20, or 40mg/kg of GMI-1271 (n=4/cohort), vs placebo control saline (n=4) or active control Lovenox 1mg/kg (n=4). The second was an open-label multiple ascending dose (MAD) study of 10 (n=3) or 20mg/kg (n=3) of GMI-1271 QD d 1-5 vs Lovenox 1mg/kg (n=2) d 1-5.Assessments included safety (adverse events [AEs], clinical labs, bleeding time, PT/PTT, vitals, exam); PK (plasma and urine); and biomarkers. Biomarkers included ELISAs (CRP, D-dimer, IL-10, MPO, Prothrombin fragment 1.2, soluble E-selectin (sEsel), soluble P-selectin (sPsel), sICAM, Thrombin-antithrombin complex (TAT), Tissue Factor (TF), TNFα, VWF activity, and sCD40L); PicoGreen Assay for circulating DNA; flow cytometry (Platelet Monocyte Aggregates (PMA), Mac-1, LFA-1, and CD44) and Thromboelastography (TEG). See Table 1 for functional description.SAD remains blinded to GMI-1271 or placebo (GMI-1271/p). In SAD, we measured biomarker values at baseline, 8 and 24 h after dosing. Analysis was performed of biomarkers at each dose level and then pooled by GMI-1271/p vs Lovenox. In MAD, we measured biomarker values at baseline and day 4. Comparisons were made using unpaired t-test.Results: In total, 32 subjects enrolled and received GMI-1271/placebo (GMI-1271/p; 20), GMI-1271 (6) or Lovenox (L; 6). SafetyAll subjects completed dosing uneventfully. Safety findings for GMI-1271/p were unremarkable. No moderate or serious AE were seen. AE overall were as expected in healthy volunteers. In SAD, only 1/20 GMI-1271/p subjects experienced an AE possibly related to study drug (mild transient headache); 0/6 in MAD. In the L group we saw expected mild transaminitis and injection site bruising. In all studies, GMI-1271 had no effect on bleeding time, PT, or PTT. PKPlasma levels, Cmax, and AUC increased in a linear manner. Cl, Vz, and t ½ were not dose dependent; no accumulation was seen with multiple dosing (Fig 1 and 2). TEGIn SAD, there was a tendency to increase R, K, and decrease A and MA with no change in % lysis in L vs GMI-1271/p. In MAD, we saw a similar trend as SAD except for an increase in % lysis in L. In the pooled SAD analysis, there was a statistically significant difference between GMI-1271/p and L (higher values) for R (p<0.001) and K (p<0.001); MA was statistically higher in GMI-1271/p vs L (p<0.05). sEselIn SAD, there was a trend for sEsel to decrease with treatment in all cohorts (combined GMI-1271/p vs L p= 0.017). In MAD, there was non-significant trend for sEsel to decrease between Day 0 and Day 4 in GMI-1271; sEsel levels trended upward with L in comparison. MPOIn SAD, there was a trend for increased values in L vs GMI-1271/p, except for the 40mg/kg cohort. When pooled, there was a significant difference between GMI-1271/p vs L (higher levels) p<0.01. In MAD, there was a non-significant trend for higher levels in L vs GMI-1271.MAC-1 In SAD, there was no change. In MAD, there was a significant decrease in MAC-1 at the 10mg/kg dose (p<0.01).No other notable trend was seen in the other biomarkers measured.Conclusion: We report a favorable safety, biomarker and bleeding profile for the E-selectin antagonist GMI-1271 in healthy subjects. There is no signal to suggest GMI-1271 increases bleeding potential based on adverse events, PT, PTT, bleeding time, and TEG values, unlike traditional anticoagulants. An additional unblinded analysis of the biomarkers will be presented at ASH. We note a trend for sE-sel to decrease with GMI-1271 treatment even in this healthy volunteer population, consistent with previous experience and as expected based on mechanism of action. A phase 1 study of GMI-1271 is currently ongoing to evaluate the safety and efficacy of E-selectin antagonism for the treatment of patients with calf vein DVT. PK FiguresFigure 1: SAD; Figure 2: MAD. [Display omitted] [Display omitted] [Display omitted] DisclosuresHemmer:GlycoMimetics, Inc.: Employment, Equity Ownership. Flanner:GlycoMimetics, Inc.: Employment. Parker:GlycoMimetics, Inc.: Employment. Li:GlycoMimetics, Inc.: Employment, Equity Ownership. Froehlich:Novartis: Consultancy; Janssen: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Fibromuscular Disease Society of America: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Merck: Consultancy. Magnani:GlycoMimetics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Thackray:GlycoMimetics: Employment, Equity Ownership. Sood:Bayer: Research Funding.

A Comparison of Socioeconomic Factors in Patients Continuing Warfarin Versus Those Transitioning to Direct Oral Anticoagulants (DOACs) for Venous Thromboembolic Disease or Atrial Fibrillation

Introduction: The regulatory approval and growing clinical acceptance of the direct oral anticoagulants (DOACs: apixaban, dabigatran, edoxaban, and rivaroxaban) has challenged warfarin as the mainstay of anticoagulation for the management of venous thromboembolic disease (VTE: deep vein thrombosis and pulmonary embolism) and atrial fibrillation/flutter (Afib). As clinicians and patients choose from the expanded menu of oral anticoagulant options, it is unknown how socioeconomic variables like income, race, gender, health insurance, or marital status may influence which anticoagulant a patient utilizes.We sought to explore if patients who stayed on warfarin differed from those who changed to a DOAC, with regard to the aforementioned socioeconomic variables. Furthermore, we desired to assess how the clinical variable of INR management, as reflected by the percent of time in therapeutic range (TTR), compared between these two groups.Methods: The Michigan Anticoagulation Quality Improvement Initiative (MAQI2) is a multi-center collaborative registry of 6 active anticoagulation clinics across Michigan. Patients newly initiating warfarin for Afib or VTE between October 2009 and July 2016 were included. Enrollees who remained on warfarin in follow-up ("non-switchers") were compared to those that transitioned to a DOAC ("switchers") on the basis of demographics, TTR by linear interpolation, race, marital status, and insurance. Patients in each group were further analyzed in quartiles based on the median household income of their zip code of residence, derived from the 2014 U.S. Census Bureau's American Community Survey. Analyses were performed using Student's t-tests and Wilcoxon Rank-sum tests for continuous variables, and chi-square and Fisher's exact tests for categorical variables.Results: 8,480 patients met the inclusion criteria, 54.4% with Afib, 45.6% with VTE, and 1.1% with both; out of this group, 675 (8%) switched from warfarin to a DOAC. There were no significant differences between switchers and non-switchers for age (mean 68.1±13.6 and 67.4±15.7, p=0.23), gender (53.9% vs. 51.5% male, p=0.23), percent TTR on warfarin (55.1% vs. 56.9%, p=0.056), or percent with commercial health insurance (33.9% vs. 34.4%, p=0.78) or uninsured (0.3% vs. 0.9%, p=0.17).Patients were more likely to switch to DOAC therapy if they had Afib vs. VTE (10.9% vs. 4.5%, p<0.001). When comparing switchers to non-switchers, switchers were more often white race (88.8% vs. 81.5%, p<0.001), married/living with a partner (68.9% vs. 59.7%, p<0.001), and had Government Health Insurance (58.9% vs. 54.6%, p=0.032). As compared to non-switchers, switchers were less often African American (7% vs. 15.3%, p<0.001), and less often had insurance through a Health Maintenance Organization (HMO) (6.9% vs. 10.2%, p=0.008). Non-switchers more often resided in a zip code with a lower median household income compared to switchers (p<0.001).Conclusion: While DOACs are often considered in patients who have difficulty maintaining a therapeutic INR, TTR was not predictive of changing from warfarin to a DOAC in this population. However, we found that SES factors, such as race, insurance status and income are associated with a patient's likelihood for switching to DOAC therapy vs. remaining on warfarin therapy. Further investigation into the reason for, and clinical impact of, these observed disparities in the care of our patients is needed. [Display omitted] DisclosuresSood:Bayer: Research Funding. Kline-Rogers:Janssen: Consultancy; ACP: Consultancy; AC Forum: Membership on an entity's Board of Directors or advisory committees. Almany:Abbott: Research Funding; Kona: Consultancy; Trice Orthopedics: Consultancy; MiCardia: Consultancy; Biostar Ventures: Equity Ownership; Ablative Solutions: Equity Ownership; Boston Scientific: Research Funding. Kaatz:Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; Daiichi Sankyo: Consultancy; Janssen: Consultancy; Boehringer Ingelheim: Consultancy; Boehringer Ingelheim: Honoraria; Janssen: Honoraria; Bristol Myer Squibb: Honoraria; Pfizer: Honoraria; CSL Behring: Honoraria. Froehlich:Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Fibromuscular Disease Society of America: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Novartis: Consultancy; Janssen: Consultancy; Merck: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees. Barnes:Portolal: Consultancy; Blue Cross Blue Shield of Michigan: Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding.

To Stent or Not to Stent? Update on Revascularization for Atherosclerotic Renovascular Disease.

Renal artery stenosis (RAS) is increasingly encountered in clinical practice. The two most common etiologies are fibromuscular dysplasia (FMD) and atherosclerotic renal artery disease (ARAS), with the latter accounting for the vast majority of cases. Significant RAS activates the renin-angiotensin-aldosterone system and is associated with three major clinical syndromes: ischemic nephropathy, hypertension, and destabilizing cardiac syndromes. Over the past two decades, advancements in diagnostic and interventional techniques have led to improved detection and the widespread use of endovascular renal artery revascularization strategies in the management of ARAS. However, renal artery stenting for ARAS remains controversial. Although several studies have demonstrated some benefit with renal artery revascularization, this has not been to the extent anticipated or predicted. Moreover, these trials have significant flaws in their study design and are hampered with inherent bias which make their interpretation challenging. In this review, we evaluate the existing body of evidence and offer an approach to the management of patients with ARAS in light of the current literature. From the data provided, identification of subgroup of patients, namely, those with a hemodynamically significant RAS in the context of progressive renal insufficiency and/or deteriorating arterial hypertension, seems possible and may derive clinical benefit from ARAS stent revascularization. Appropriate patient selection is therefore the key and more robust studies are required.

Ischemic renal disease and renal artery stenosis

Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary or transplant kidney, renal insufficiency (ischemic renal disease) or rarely pulmonary flash edema may occur. In most cases arteriosclerotic disease is the underlying cause; less prevalent are the various manifestations of fibromuscular disease. Renal artery stenosis may be treated by revasularization, using either percutaneous (balloon angioplasty, stenting) or rarely open surgical procedures, both with excellent primary patency rates. However, randomized trials of renal artery angioplasty or stenting in patients with arteriosclerotic lesions have failed to demonstrate a longer-term benefit with regard to hypertension control and renal dysfunction over medical management alone. Careful patient selection is essential to maximize the potential benefit (e.g., in patients with refractory hypertension, progressive renal failure or recurrent pulmonary flash edema).

Basic Data Underlying Decision Making in Nonatherosclerotic Causes of Intermittent Claudication

Although most cases of vasculogenic intermittent claudication are caused by atherosclerosis, there is an important minority of cases that are due to nonatherosclerotic causes. Because of their rarity and younger population affected, often without traditional atherosclerotic risk factors, there is frequently a significant delay in diagnosis of nonatherosclerotic peripheral arterial diseases by several months to years in some cases. Here, we review the literature on nonatherosclerotic causes of lower extremity claudication, symptoms, management including surgical and endovascular interventions, and outcomes. Conditions included are popliteal artery entrapment syndrome, cystic adventitial disease, pseudoxanthoma elasticum, persistent sciatic artery, fibromuscular disease, giant cell arteritis, iliac endofibrosis, neurogenic claudication, and chronic exertional compartment syndrome.

Aktuelle Strategien in der Therapie der Nierenarterienstenose

Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary kidney, renal insufficiency (ischemic kidney disease) or rarely pulmonary flush edema may occur. Renal artery stenosis may be treated by revascularization, using either percutaneous (balloon angioplasty, stenting) or less common open surgical procedures, both with excellent primary patency rates. However, randomized trials of renal artery angioplasty or stenting have failed to demonstrate a longer-term benefit with regard to blood pressure control and renal function over medical management alone (except for fibromuscular disease). Furthermore, endovascular procedures are associated with substantial risks. It has not yet been demonstrated that renal revascularization leads to a prolongation of event-free survival. Careful patient selection is essential to maximize the potential benefit.

Onyx Embolization of High-Flow Spontaneous Cervical Vertebral Arteriovenous Fistula

High-flow spontaneous vertebral arteriovenous shunts in patients with fibromuscular disease (FMD) are rare. Onyx embolization of the recipient veins with shunt disconnection and preservation of the affected vertebral artery in a patient with FMD has not been reported. A 59-year-old female presented with progressive dizziness, pre-syncopal episodes, and tinnitus. Catheter-based angiography identified features of fibromuscular dysplasia and a high-flow right cervical vertebral artery arteriovenous shunt. Onyx embolization of the principle draining veins was performed with initial detachable coil placement. Complete disconnection of the shunt was achieved without sacrifice of the parent vertebral artery. Spontaneous high-flow vertebral arteriovenous shunts can be successfully occluded with Onyx/detachable coil embolization of the principle recipient veins.

PS178. Non-operative Treatment of Spontaneous Visceral Artery Dissection

Spontaneous visceral artery dissection (SVAD) is rare, and little is known about its natural history. Our goal is to determine early and late outcomes of patients managed non-operatively. A retrospective review of all consecutive patients with visceral artery dissection confirmed by imaging from 1990 to 2011. Patients with SVAD associated with fibromuscular disease, vasculitis, and iatrogenic or traumatic injury were excluded. Sixty-one men and 28 women ( mean age 54 +/- 12 years ) were treated for SVAD over 20 years. Eighty-one patients were Caucasian (96%); comorbidities included hypertension (60%), hyperlipidemia (47%), and smoking (45%). Sixty patients (67%) presented with abdominal pain or GI symptoms; 29 were asymptomatic (33%) with dissection discovered incidentally. Diagnosis was confirmed by CTA in most patients. SVAD involved an average of 2.4 +/- 2.2 vessels per patient with celiac territory involvement in 61%, SMA in 43%, and both in 27%. Average WBC was 7.9 (Normal range 4-10), CRP 4.9 (Normal <10), and ESR 16.5 (Normal <20). Seventy-three patients were managed successfully medically with initiation of anti-hypertensives in 22 (25%), anti-coagulation in 21 (24%), and aspirin in 14 (16%). Seventeen (19%) patients underwent intervention (13 surgical, 4 coil embolization) at diagnosis; 6 for rupture, 7 for worsening symptoms, and 4 for enlarging aneurysms or dissections. There were no peri-procedural deaths within 30 days. Six patients died over a mean follow-up of 5.9 +/- 3.2 years. On surveillance imaging, the majority of dissections remained stable or resolved. Estimated survival at 1, 3, 5, and 10 years was 100%, 94%, 94%, and 65%. SVAD is a rare disease. Most Caucasian patients with this problem can be treated medically with good long-term survival. Operation and/or endovascular therapy is necessary for rupture or persistent symptoms despite maximum medical therapy.

Diagnosis of non-atherosclerotic carotid disease

Summary Non-atherosclerotic carotid disease in an uncommon group of angiographic defects. It includes the entities: Takayasu's arteritis, giant cell arteritis, fibromuscular disease, moyamoya syndrome, arterial dissection and extracranial carotid aneurysms. Due to advance in imaging techniques, they are being increasingly identified. Growing awareness of diverse clinical picture along with advances in imaging technologies enables early diagnosis. Although catheter angiography is a gold standard in diagnosing most of these diseases, neurosonological tests serve as an excellent screening tool, and are suitable for monitoring. Brain MR and MRA are sometimes essential for confirmation of the diagnosis. Mortality rates are low and functional outcome is generally good if the disease is diagnosed early.

Endovascular treatment of bilateral internal carotid artery aneurysm

BACKGROUND: Aneurysms of the extra cranial internal carotid artery (ICA) are rare and caused by infection, arteriosclerosis, fibro muscular dysplasia, neurofibromatosis, Behcet disease, Ehlers-Danlos syndrome, radiotherapy, iatrogenic injury or trauma. Increasing number of high-risk patients and more accurate diagnosing of unapproachable lesions make the consideration of endovascular treatment more acceptable. METHODS: We are reporting a case of a 36-year-old male with bilateral aneurysms of ICA and a history of several transitory ischemic attacks. Bilateral successive implantation of a 19 mm long covered stent (Jostent) was performed, with a delay of one month between the two procedures. After exclusion of the right ICA with covered stent, patient developed transitory ischemic attack and control multi detector computed tomography revealed occlusion of the left ICA. RESULTS: Further recovery of the patient was uneventful and a control examination after 2 years show patent right ICA, occluded left ICA with no clinical consequences. CONCLUSIONS: Patients with recurrent symptoms associated with extra cranial aneurysm need prompt treatment. Surgical resection with various reconstruction techniques is established method. Endovascular exclusion by covered stent in surgically unapproachable aneurysms is feasible; however, there is still need for more technical improvement and experience before it becomes preferable treatment option.

Late Outcomes of Endovascular and Open Revascularization for Nonatherosclerotic Renal Artery Disease

Conclusion: In patients with nonatherosclerotic renal artery disease (NARAD), open revascularization results in superior 1- and 5-year outcomes compared with endovascular management. Summary: Fibromuscular dysplasia and Takayasu arteritis are the most common etiologies of NARAD leading to hypertension. Open or endovascular revascularization is preferred over medical management alone in patients with severe hypertension associated with NARAD. Percutaneous transluminal angioplasty (PTA) is generally considered first-line therapy for fibromuscular disease, whereas open revascularization is generally thought to be the best treatment for patients with Takayasu arteritis. The purpose of this report was to evaluate long-term outcomes of endovascular and open treatment of NARAD. This was a retrospective review of 55 patients (47 women), with a mean age of 40 years. Underlying disease processes included Takayasu arteritis in 31 patients and fibromuscular dysplasia in 24. Open revascularization was compared with renal artery PTA, with and without stenting, for primary, primary assisted, and secondary patency rates as well as blood pressure, antihypertensive medication requirements, renal function, and mortality. Among the 79 renal artery interventions performed were 59 aortorenal bypasses (16 ex vivo), 3 visceral-to-renal artery bypasses, 5 nephrectomies, and 12 endovascular percutaneous revascularizations, 4 of which included stent placement. There were no procedural deaths. Mean follow-up was 75 months. Rates of primary patency at 1, 3, and 5 years for any intervention were 87%, 75% and 75%, respectively. Primary, primary assisted, and secondary patency rates were 92%, 86%, and 86%, respectively. Primary patency rates for endovascular interventions at 1, 3, and 5 years were 73%, 49%, and 49%. Primary assisted/secondary patency rates for endovascular interventions were 83%, 83%, and 83% at 1, 3, and 5 years. At 1, 3, and 5 years, primary patency rates for open revascularization were 91%, 80%, and 80%. Primary assisted/secondary patency rates for open interventions at 1, 3 and 5 years were 94%, 87%, and 87%, respectively. Open and endovascular interventions both resulted in improvements in blood pressure and the number of antihypertensive medications compared with preintervention values (all P < .05). Revascularization also improved serum creatinine levels and estimated glomerular filtration rate (both P < .05). The 5- and 10-year actuarial survival rates were 94% and 78%, respectively. Comment: The authors demonstrated open and endovascular intervention can be safe and effective in management of renal artery-mediated hypertension and renal dysfunction associated with NARAD. The patients are not randomized, and any conclusions are somewhat weakened by the study design, but in general, the data indicate primary open revascularization, when compared with endovascular intervention, results in superior outcome with respect to patency with equivalent safety. The authors' conclusion is that open revascularization should be considered selectively as first-line of therapy for NARAD in the young patient with moderate to complex renal artery disease. This conclusion is clearly suggested but not confirmed by the data.

“Re: Renal Artery Stenting is no Longer Indicated After ASTRAL: Pros and Cons”

The authors of the ASTRAL trial [1] were interested to read the debate about the trial in CVIR [2]. They have listened with some bemusement to the criticisms that have been levelled at the study in this debate and other publications [3]. Although constructive criticism and intelligent debate is healthy, it appears that many are confused about the methodology and results of the ASTRAL Trial. It is important to be clear that after years of small case series, cohorts, and randomized, controlled trials, ASTRAL succeeded in randomizing a significant number of patients with chronic renal impairment to renal stenting and best medical therapy against best medical therapy alone. It is more than 7.5-times larger than the previous largest reported study [4]. This was quite an achievement. Some critics of ASTRAL did not enter any patients into the trial, either because they were never ‘‘uncertain’’ how to treat their patients (lucky them) or they misunderstood the ‘‘uncertainty principle.’’ Patient eligibility based on the ‘‘uncertainty principle’’ has been widely used in a number of trials [5] and is scientifically and ethically acceptable in those situations where a clinician is uncertain how to treat a patient. This principle resulted in a heterogeneous patient population being entered into the trial, as different clinicians had different areas of uncertainty regarding the use of renal stenting. One of the criticisms levelled at ASTRAL is that many patients (and especially patients considered likely to benefit from renal stenting) were not entered into the trial. However, randomization is only ethically justified if one is unsure of the benefits of intervention to the individual patient. In the event, the patients recruited to ASTRAL did not have trivial disease. The majority had severe renal artery stenosis and/or impaired renal function. Randomization was stratified according to disease severity and the number in each prespecified subgroup was substantial (often larger in patient numbers than the previous trials). We found no evidence of benefit for renal stenting in any of the subgroup analyses or in the post-hoc analysis of the most severe patients. Those who criticize the ASTRAL trial on the basis that it excluded those patients who were likely to benefit from intervention have misunderstood the uncertainty principle. It is impossible to know why individual patients were excluded, but it is likely that many patients with accepted indications for intervention, such as acute anuric renal failure, very rapid decline in renal function, malignant hypertension, and flash pulmonary edema, were not randomized. Fibromuscular disease was a specific exclusion criterion. Critics should recognize that ASTRAL is not at a variance with all the previous small studies mentioned above. In fact many of these results are supported by the ASTRAL analyses. The difference between ASTRAL and these other studies is that nearly all of the patients in ASTRAL were taking best medical therapy. Quite simply, the benefits attributed to angioplasty or stenting in previous studies could be achieved by best medical therapy alone. It is important to recognize that no other study on renal artery N. Chalmers (&) Department of Radiology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK e-mail: Nicholas.chalmers@cmft.nhs.uk

Clinical management of atheromatous renovascular disease

Renal artery stenosis (RAS) is common, being due to atheroma in over 90% of cases in developed countries with the remainder mainly due to fibromuscular disease (FMD). The latter tends to occur in younger patients, predominantly women, and usually presents with severe hypertension; a good outcome can

Renovascular Hypertension: Lesion Detection, Patient Selection, Treatment Options and Results

Renal artery stenosis (RAS) causing either renovascular hypertension (RVH) or ischemic nephropathy (IN) is a complicated pathophysiologic entity. The diagnosis may remain uncertain in many cases and is frequently obscured by other overlapping sources of hypertension. Improved sensitivities of non-invasive diagnostic imaging modalities has led to an increase in the detection of RAS without necessarily guiding treatment recommendations. Simultaneously, widespread, multidisciplinary competence with minimally-invasive, catheter-based therapies has led to frequent treatment of RAS without clearcut benefit. Establishing a causal relationship between the renal artery lesion and hypertension, when feasible, is of paramount importance in recommending therapy and achieving expected results. Broad lesion classification and location is also helpful in guiding therapies when indicated. Developmental lesions of the renal arteries typical of RVH affecting children behave differently than typical fibromuscular dysplastic (FMD) lesions or atherosclerotic renal artery disease (ASO-RAS). Unilaterality versus bilaterality, ostial versus branch vessel, focal versus diffuse and renal functional status are equally important in recommending therapy. Renovascular surgery and results of renal artery angioplasty /stenting (RAA) are discussed in the context of outcomes and durability. Ongoing investigations examining results of catheter-based treatments of RAS utilizing embolic protection devices (EPD) are presently in the forefront of the current literature and discussed in this review.

Renal infarction resulting from traumatic renal artery dissection

Renal artery dissection may be caused by iatrogenic injury, trauma, underlying arterial diseases such as fibromuscular disease, atherosclerotic disease, or connective tissue disease. Radiological imaging may be helpful in detecting renal artery pathology, such as renal artery dissection. For patients with acute, isolated renal artery dissection, surgical treatment, endovascular management, or medical treatment have been considered effective measures to preserve renal function. We report a case of renal infarction that came about as a consequence of renal artery dissection.

Diagnosis and Management of Renovascular Disease and Renovascular Hypertension

Renovascular disease is a common but complex disorder, the most common causes of which are fibromuscular dysplasia and atherosclerosis. Clinically, it can present as asymptomatic renal artery stenosis, renovascular hypertension, or ischemic nephropathy. Assessing the clinical index of suspicion remains essential in determining an appropriate diagnostic strategy. For diagnosis in patients with suspected fibromuscular disease, it may be reasonable to proceed directly to renal angiography; however, for most patients with suspected atherosclerotic disease, there are a number of noninvasive tests available that can aid in decision making. The choice of the most appropriate initial test should be based on patient characteristics, clinical presentation, and local expertise. Treatment options include medical, surgical, or percutaneous approaches. Generally, in patients with fibromuscular disease, percutaneous intervention provides durable improvement or cure of hypertension. In patients with atherosclerotic disease, the data are less consistent, and there does appear to be a group of patients who will respond well to medical management alone. As technology advances, the diagnostic and treatment paradigms will continue to evolve.