Previous Peripheral Arterial Disease Research Articles

Long-term clinical and imaging outcomes of patients undergoing percutaneous femoral intervention following TAVI-related vascular access complications

Abstract Introdcution: Vascular access complications (VAC) are the most common in-hospital adverse event following transcatheter aortic valve implantation (TAVI). Often, ileo-femoral VAC requires bail-out percutaneous interventions with either prolonged balloon inflation and/or stent implantation. The long-term outcomes of these procedures have not been characterized. We aim to assess the clinical and imaging outcomes of patients who underwent bailout percutaneous vascular interventions due to VAC following TAVI. Methods Single-centre prospective study including all consecutive patients with a VAC following trans-femoral TAVI, between 2015-July 2023. VAC was defined as uncontrolled bleeding, acute occlusion or flow limiting stenosis of the femoral vessel leading to percutaneous treatment. Clinical and imaging follow-up was performed with bilateral arterial ultrasound (US) Doppler to assess patency and peak systolic velocity of common femoral arteries. Results A total of 1518 patients underwent TF-TAVI, of which 107 (7%) underwent concomitant ileo-femoral percutaneous angioplasty (PTA) intervention in the same day as TAVI. In patients submitted to PTA, 7 were treated to gain access for TAVI, and 100 (7%) were performed to treat vascular access complications. At a mean follow-up time of 23±3 months, 37 patients died (37%), 6 (16%) from in-hospital complications and 31 (84%) from non-vascular causes after discharge. From the surviving 63 patients (study group) – mean age 83±6 years-old, 29% male, 46% with previous peripheral arterial disease –, 24 underwent bilateral US. Unable to perform imaging on 39 patients due to geographical or mobility issues. At a mean follow-up time of 30±23 months, only 6 patients (10%) reported intermittent claudication, of which 4 (67%) had pre-TAVI symptoms. No patient had at rest symptoms or amputation history. All but one had patent vessel on US. The mean peak systolic velocity of the treated vessel and the contralateral vessel were 71.1±22.9cm/s and 73.1±23.8cm/s, respectively, with no statistically significant difference between them in each patient (mean difference 1.9±25.4, p=0.709). We found no statistically significant differences between peak systolic velocities between both vessels in each patient, accordingly with the treated vessel (Table 2). Conclusion This prospective study shows that patients submitted to percutaneous bailout iliofemoral interventions have a very low rate of lower limb adverse events with very good patency rates at mean follow up of 2.5 years.

Short- and long-term effects of the COVID-19 pandemic on patients with cardiovascular diseases: A mini-review

The COVID-19 pandemic had profound implications for patients with cardiovascular diseases (CVDs), both in the short- and long-term. In this article, we provide an overview of the effects of the pandemic on individuals with preexisting cardiovascular conditions. In the short term, the severe acute respiratory syndrome coronavirus 2 infection increased the risk of many cardiovascular events. Furthermore, the pandemic has disrupted health-care systems worldwide, leading to constraints in routine care, and limited access to specialized cardiovascular services and procedure. This has resulted in increased morbidity and mortality rates among patients with CVD (coronary artery disease, hypertrophic cardiomyopathy, heart failure (HF), heart transplant recipients, atrial fibrillation, atrial flutter, previous stroke, or previous peripheral artery disease). In the long term, the COVID-19 impact on patients with CVD extends beyond the acute phase of the disease. Studies have highlighted the development of long-term cardiovascular complications in COVID-19 survivors, such as acute coronary syndrome myocarditis, HF, stroke, venous thromboembolism, and arrhythmias, which may lead to a surge of new cases associated with CVD in the postpandemic era. Health-care systems must prioritize cardiovascular care, developing strategies to identify the patients at higher risk and provide the care to minimize the impact of the pandemic on patients with CVD.

2MACE score predicts cardiovascular adverse events in real-world atrial fibrillation patients under rivaroxaban therapy. Data from EMIR study

Abstract Background Atrial Fibrillation (AF) patients have higher risk of major adverse cardiovascular events (MACEs). In 2015, the 2MACE score (2 points for metabolic syndrome and age ≥75, and 1 point for myocardial infarction [MI] or revascularization, congestive heart failure [ejection fraction ≤40%] and thromboembolism [stroke or transient ischemic attack]) was described to stratify cardiovascular risk and 2MACE≥3 was related with high risk of MACE in AF patients but a long-term validation in prospective patients under direct anticoagulants has not been performed yet. The aim of this study was to analyse the incidence of cardiovascular events and to validate the 2MACE score as predictor of MACEs. Methods EMIR study [acronym from 'Estudio observacional para la identificaciόn de los factores de riesgo asociados a eventos cardiovasculares Mayores en pacientes con fIbrilaciόn auricular no valvular tratados con un anticoagulante oral directo (Rivaroxaban)'] was an observational, multicenter, post-authorization and prospective study that involved AF patients under oral anticoagulation with rivaroxaban at least 6 months before enrolment. We analyzed baseline clinical characteristics and adverse events after 2.5 years of follow up: annual incidence of thromboembolic events, MACE (composite of nonfatal MI, coronary revascularization and cardiac death) and cardiovascular mortality were analyzed. Results We analyzed 1,433 patients (55.5% women, mean 74.2±9.7 years). 385 (26.9%) patients had 2MACE score ≥3 and of those high-risk patients, 42.1% had previous coronary disease, 12.5% had previous peripheral artery disease, 40.7% had diabetes mellitus, 39% heart failure and 50% had chronic kidney disease (GFR<60 ml/min). After 2.5 (2.2–2.6) years of follow-up, we observed patients with 2MACE score ≥3 had higher rate of adverse events (Table), specially of higher rate of cardiovascular mortality and MACE. Patients with 2MACE score ≥3 had RR 4.09 (2.59–6.45; p<0.001) for MACE. Indeed, patients with 2MACE score ≥3 had around 6-fold risk of cardiovascular death due heart failure than patients with 2MACE score <3 (0.17%/year vs 1.09%/year; p=0.003). 2MACE score had suitable predictive performance for MACE (AUC 0.638 [(0.534–0.742); p=0.010). Conclusion In a Real-world AF patients under rivaroxaban therapy from EMIR registry, the 2MACE score is a good predictor of long-term cardiovascular events, MACE and major bleeding. A 2MACE score ≥3 categorize patients at “high-risk” with almost 4-fold risk of MACE in a long-term follow-up. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer Hispania S.L. Table 1. Adverse events according to 2MACE

European differences in characteristics, treatments and outcomes in patients with non-ST-elevation myocardial infarction – novel insights from four national real-world registries

Abstract Background Large-scale collection of standardized variables in patients with myocardial infarction (MI) in national real-world registries are only available in a few European countries and there is lack of cross-country comparisons. Purpose To compare demography, risk factors, hospital treatment and short- and long-term survival in patients hospitalized for non-ST elevation MI (NSTEMI) in four different European countries. Methods NSTEMI patients hospitalized and enrolled in national MI registries; EMIR (Estonia), HUMIR (Hungary), NORMI (Norway (2013–2016)) and SWEDEHEART (Sweden) from 2014 to 2017 were included. Results In total 119,191 patients with NSTEMI were included. The mean age at admission ranged from 70 years (Hungary) to 75 years (Estonia). The proportion of women was 36% in Sweden and 44% in Estonia. In Norway 24% were smokers, as compared to 17% in Sweden. Patients in Hungary had a high rate of diabetes mellitus (37%) and antihypertensive treatment (84%) but a low rate of lipid lowering treatment (32%). The proportion of patients with prior MI ranged from 28% (Norway) to 37% (Sweden). The presence of previous peripheral artery disease ranged from 7% (Sweden) to 17% (Hungary). The absolute proportion of performed coronary angiographies (58% versus 75%) and percutaneous coronary interventions (38% versus 56%), differed most between Norway and Hungary. Dual antiplatelet therapy ranged from 60% (Estonia) to 81% (Hungary) and statins from 78% (Norway) to 89% (Hungary), at discharge. The crude mortality rates at 1 month and 1 year are listed in table 1. Conclusion Cross-comparison of four national European MI registries provide new insights in differences in risk factors, treatment and outcomes. Possible reasons for the observed differences, include differences in the underlying expected mortality in the populations, inclusion-criteria and coverage of the registries and variable definitions, that need to be further explored. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Estonian Research Council

Procedural Characteristics and Late Outcomes of Percutaneous Coronary Intervention in the Workup Pre-TAVR.

This study sought to determine, in patients undergoing percutaneous coronary intervention (PCI) during the work-up pre-transcatheter aortic valve replacement (TAVR): 1) the clinical and peri-procedural PCI characteristics; 2) the long-term outcomes; and 3) the clinical events in those patients with complex coronary features. A PCI is performed in about 25% of TAVR candidates, but procedural features and late outcomes of pre-TAVR PCI remain largely unknown. Multicenter study including 1197 consecutive patients who had PCI in the work-up pre-TAVR. A total of 1,705 lesions (1.5 ± 0.7 lesions per patient) were included. Death, stroke, myocardial infarction, and major adverse cardiovascular and cerebrovascular events (MACCE) were recorded, as well as target lesion failure (TLF) and target vessel failure (TVF). One-half of patients exhibited a multivessel disease and the mean SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) score was 12.1 ± 9.1. The lesions were of B2/C type, calcified, bifurcation, and ostial in 49.9%, 45.8%, 21.4%, and 19.3% of cases, respectively. After a median follow-up of 2 (interquartile range: 1 to 3) years, a total of 444 (37.1%) patients presented an MACCE. Forty patients exhibited TVF (3.3%), with TLF identified in 32 (2.7%) patients. By multivariable analysis, previous peripheral artery disease (p<0.001), chronic obstructive pulmonary disease (p=0.002), atrial fibrillation (p=0.003), diabetes mellitus (p=0.012), and incomplete revascularization (p=0.014) determined an increased risk of MACCE. In patients with unprotected left main or SYNTAX score >32 (n=128), TLF, TVF, and MACCE rates were 3.9%, 6.3%, and 35.9%, respectively (p=0.378; p=0.065, and p=0.847, respectively, vs. the rest of the population). Patients undergoing PCI in the work-up pre-TAVR frequently exhibited complex coronary lesions and multivessel disease. PCI was successful in most cases, and TLF and TVF rates at 2-year follow-up were low, also among patients with high-risk coronary features. However, overall MACCE occurred in about one-third of patients, with incomplete revascularization determining an increased risk. These results should inform future studies to better determine the optimal revascularization strategy pre-TAVR.

Temporal trends in the premorbid use of preventive treatments in patients with acute ischemic cerebrovascular events and a history of vascular disease: The Dijon Stroke Registry (1985–2010)

Although secondary prevention in patients with arterial vascular diseases has improved, a gap between recommendations and clinical practice may exist. We aimed to evaluate temporal trends in the premorbid use of preventive treatments in patients with ischemic cerebrovascular events (ICVE) and prior vascular disease. Patients with acute ICVE (ischemic stroke/TIA) were identified through the population-based stroke registry of Dijon, France (1985-2010). Only those with history of arterial vascular disease were included and were classified into four groups: patients with previous coronary artery disease only (CAD), previous peripheral artery disease only (PAD), previous ICVE only, and patients with at least two different past vascular diseases (polyvascular group). We assessed trends in the proportion of patients who were treated with antihypertensive treatments and antithrombotics at the time of their ICVE using multivariable logistic regression models. Among the 5309 patients with acute ICVE, 2128 had a history of vascular disease (mean age 77.3±11.9, 51% men; 25.1% CAD 7.5% PAD, 39.8% ICVE, and 27.5% poylvascular). A total of 45.8% of them were on antithrombotics, 64.1% on antihypertensive treatment, and 34.4% on both. Compared with period 1985-1993, periods 1994-2002 and 2003-2010 were associated with a greater frequency of prior-to-ICVE use of antithrombotics (adjusted OR=5.94; 95% CI: 4.61-7.65, P<0.01, and adjusted OR=6.92; 95% CI: 5.33-8.98, P<0.01, respectively) but not of antihypertensive drugs. Consistent results were found when analyses were stratified according to the type of history of arterial vascular disease. Patients with ICVE and previous vascular disease were still undertreated with recommended preventive therapies.

Cumulative Number of Treatment Interventions Predicts Health-Related Quality of Life in Patients with Critical Limb Ischemia

Health-related quality of life (QOL) is usually assessed after a defined interval following a single intervention, but critical limb ischemia (CLI) is a chronic condition where multiple interventions are often required over a patient's lifetime. We hypothesized that the impact of CLI treatment interventions on QOL is diminished in the setting of multiple previous interventions. To test this hypothesis, we performed a cross-sectional study evaluating associations between cumulative number of previous peripheral artery disease (PAD) treatment interventions and QOL adjusting for both comorbidity and disease severity. Participants with CLI (abnormal ankle brachial index [ABI] plus rest pain and/or tissue loss) were enrolled in a cross-sectional study and completed a disease-specific QOL assessment, (the Vascular Quality of Life Questionnaire-6 [VascuQol-6]). Minimum ABI was used to assess disease severity, and comorbidity was evaluated based on Charlson Comorbidity Index. Cumulative number of PAD treatment interventions was defined based on the lifelong total for both legs. QOL associations were evaluated using a multivariable linear regression model adjusted for age and gender. Thirty-two patients with CLI participated. Mean age was 63±10years, 72% were men, and 63% were white; mean ABI was 0.6±0.2. Mean VQ-6 score was 11.6±4.2, and QOL was lower in patients with more previous interventions. Multivariable models demonstrated that an increasing number of previous treatment interventions negatively impacted QOL (P=0.047), whereas positive associations were identified for female gender (P=0.006) and ABI (P=0.006). No association between comorbidity and QOL was identified. Vascular-specific factors appear to be key determinants of QOL among patients with CLI, whereas comorbidity appears less important. Strategies focused on definitive and durable revascularization may reduce cumulative interventions and potentially maximize QOL for patients with CLI.

Subjective health complaints predict functional outcome six months after stroke.

ObjectivesCerebrovascular stroke is a main cause of lasting disability in older age, and initial stroke severity has been established as a main determinant for the degree of functional loss. In this study, we searched for other predictors of functional outcome in a cohort of stroke patients participating in an early supported discharge randomised controlled trial.MethodsThirty candidate variables related either to premorbid history or to the acute stroke were examined by ordered logistic regression in 229 stroke patients. Dependent variables were modified Rankin Scale (mRS) at 6 months and mRS change from baseline to 6 months.ResultsFor mRS at 6 months, Barthel Index at stable baseline post‐stroke was the main predictor, with sex, age, previous cerebrovascular disease, previous peripheral artery disease and the necessity for tube feeding in the acute phase also contributing to the final model. For mRS change, only age and previous cerebrovascular disease were significant predictors. Prestroke subjective health complaints added significantly to all final models concurrently with sex losing its predictive power.ConclusionsInitial stroke severity was the main predictor of functional outcome. Subjective health complaints score was a potent predictor for both outcome and improvement from baseline to 6 months and at the same time ameliorated the predictive impact of sex. The poorer functional prognosis for women after stroke may therefore be related to their higher load of subjective health complaints rather than to their sex itself. Treating these complaints may possibly improve the functional prognosis.

A single center experience of Zilver PTX for femoro-popliteal lesions

Clinical trial data show overall favorable outcomes of paclitaxel-eluting stents for treatment of femoro-popliteal (FP) occlusive disease. However, external validity of trial results may be restricted to less complex FP lesions, and limited data on outcomes of paclitaxel-eluting stents in real world practice have been published. This is a retrospective analysis of data of all patients who received Zilver® PTX® for FP lesion from February 2013 to October 2014 at our center. The primary endpoint was primary patency, defined as peak systolic velocity ratio <2.0 by Doppler ultrasound, or angiographic diameter stenosis <50%, or freedom from clinically driven target lesion revascularization. Seventy-eight patients received Zilver® PTX® for FP lesions in the pre-specified time period. Of them, 63 had follow-up data and were included in this study. Mean patient age was 66.3±9.4years, and 57.1% of the patients were men. Participants had a high prevalence of diabetes (49.2%), hypertension (93.7%), hyperlipidemia (93.7%), previous coronary revascularization (52.4%), or previous peripheral arterial disease (77.8%). Critical limb ischemia was present in 25.4% of the patients, Trans-Atlantic Inter-Society Consensus (TASC) class C or D in 76.2%, in-stent restenosis (ISR) in 36.5%, and total occlusion in 69.8%. Mean lesion length was 218.9±128.3mm, mean number of stents was 2.02±1.0, and total stent length was 189.0±128.5mm. Mean follow-up was 270.4±190.3days. Primary patency rate at 1year was 66.7% by Kaplan-Meier survival curve. When compared with patients with primary patency at follow up, those with an adverse outcome had higher prevalence of TASC II class C or D lesions (100% vs. 68.8%, p=0.013), and were more likely to have ISR (66.7% vs. 27.1%, p=0.012), longer lesion (291.3±138.7 vs. 195.7±117.1, p=0.011), and incomplete coverage of the lesion (full coverage of lesions: 40% vs. 77.1%, p=0.011). Post marketing use of Zilver® PTX® for the treatment of FP lesions is associated with lower patency rates compared with clinical trial data. This may be related to the high prevalence of TASC II class C or D lesions and ISR in real world practice. Future studies should be more representative of contemporary clinical practice.

Procedural outcomes of chronic total occlusion percutaneous coronary intervention: a report from the NCDR (National Cardiovascular Data Registry).

The aim of this study was to describe contemporary frequency, predictors, and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in the United States. CTO PCI can provide significant clinical benefits, yet there is limited information on its success and safety in unselected patient populations. We analyzed the frequency and outcomes of CTO PCI compared with non-CTO PCI in elective patients, and of successful versus failed CTO PCI between July 1, 2009, and March 31, 2013, in the National Cardiovascular Data Registry CathPCI Registry. Generalized estimating equations logistic regression modeling was used to generate independent variables associated with procedural success and procedural complications. During the study period, CTO PCI represented 3.8% of the total PCI volume for stable coronary artery disease (22,365 of 594,510). Overall, patients undergoing CTO PCI required greater contrast volume and longer fluoroscopy time and had lower procedural success (59% vs. 96%, p < 0.001) and higher major adverse cardiac event (1.6% vs. 0.8%, p < 0.001) rates than non-CTO PCI patients. On multivariable analysis, several parameters (including older age, current smoking, previous myocardial infarction, previous coronary artery bypass graft, previous peripheral arterial disease, previous cardiac arrest, right coronary artery CTO target vessel, and less operator experience) were associated with a lower likelihood of CTO PCI procedural success, whereas operators' annual CTO PCI volume was associated with improved success without a significant increase in major complications. CTO PCI is currently performed infrequently in the United States for stable coronary artery disease and is associated with lower procedural success and higher complication rates compared with non-CTO PCI. Procedural success was associated with several patient factors and operator experience.

Importancia de la carga vascular previa en la mortalidad intrahospitalaria y a largo plazo de pacientes con infarto de miocardio y segmento ST elevado

Introduction and objectivesPatients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up. MethodsProspective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease («vascular burden») were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality. ResultsOne vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P=.34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844). ConclusionsIn patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge.Full English text available from: www.revespcardiol.org/en

Impact of Previous Vascular Burden on In-hospital and Long-term Mortality in Patients With ST-segment Elevation Myocardial Infarction

Introduction and objectivesPatients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up. MethodsProspective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease («vascular burden») were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality. ResultsOne vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P = .34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844). ConclusionsIn patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge.

Analysis of Clinical Arterial and Metabolic Parameters in Chronic Phase CML Patients On Nilotinib in a Single Center Cohort

AbstractAbstract ▪3756▪This icon denotes a clinically relevant abstractThe introduction of second generation tyrosine kinase inhibitors (TKI2) in the treatment of chronic phase chronic myelogenous leukemia (CML) has improved the response rates in the second, and now, in the first line setting. Nilotinib, a TKI2 with a restricted kinase inhibition profile, demonstrated higher rates of response over imatinib (IM) as front line therapy with a very good short-term tolerability profile. Even if the proportion of patients (pts) in undetectable disease increases with time, the majority will have to continue this treatment for several yrs to avoid progression. In this perspective, mid- and long-term safety issues are of concern, and recent reports point out the onset of arteriopathies in such pts with a suspected abnormal frequency.We have prospectively analysed our on-nilotinib cohort of CP CML between September 2011 and July 2012 with standard clinical assessments [height, weight, body mass index (BMI), ankle-brachial index (ABI)], and basic routine metabolic laboratory assessments (fasting glucose, total, HDL and LDL cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glycosylated hemoglobin) and BCR-ABL (IS), to explore and detect at early stages abnormalities that may have some later cardio-vascular consequences for pts on this drug.We analysed a series of 54 CML pts all in CP. The median age at diagnosis was 50 (18–73) and 55 (20–78) yrs at nilotinib initiation. The Sokal score was low for 27%, intermediate for 55%, high for 8%, unknown for 10 pts. At CML diagnosis, 13 pts had hypertension, 4 diabetes mellitus, 2 previous peripheral arterial disease (PAD), 4 coronary artery disease (CAD), and 9 pts had tobacco addiction. Thirty-seven pts had IM first line for a median of 4.2 (0.2–11) yrs, then nilotinib for IM-intolerance (14 pts) or IM-resistance (16 pts), or entering a clinical trial (5 pts) and 2 for unknown reasons for a median of 2.8 (0.5–5.6) yrs. Seventeen pts had nilotinib first line for a median of 1 (0.3–4.7) year. The disease duration ranged from 0.4 to 19.3 yrs (median 5.6). Overall, the median duration of nilotinib was 2.2 (0.3–6.8) yrs. Two pts were in CHR, 11 pts in CCyR, 28 in MMR, 13 in undetectable disease (MR4.5) at assessment. In pts on nilotinib without statins at time of assessment, 62% (n=40) showed high total cholesterol values (>2 g/l), 46% (n=37) had high LDL cholesterol (>1.5 g/l) and 57% (n=37) low HDL cholesterol values (<0.6 g/l). Triglycerides were high (>1.48 g/l) in 18% of pts (n=49). Glycosylated hemoglobin was high (>6%) in 18% of the pts treated (n=38), and glucose (> 5.8 mmol/l) in 20% (n=11). Seven pts (13%) were overweight (BMI>30) and the median BMI was 24.6 (16.7–47). On 54 pts, 25% of pts (n=13) had an abnormal ABI (<1) and true arterial problems were authentified by Doppler ultrasound in 13% (n=7) of pts after a median of 2.6 (0.6–4.4) yrs of nilotinib: carotid atherosclerosis, inflammatory carotiditis, one CAD, 4 PADs, with 5 newly diagnosed on nilotinib. In order to correlate the different parameters together we use the correlation circle strategy (see figure 1 below) resulting from the principle components analysis (PCA), in this circle each arrow represents a studied parameter, and the closest one parameter is to another one, the closest the arrows are. Perpendicular arrows denote no correlation at all. The length of each arrow depends on the weight of each parameter compared to the others within the PCA. [Display omitted] As seen; there is a strong correlation between the duration of nilotinib and the total cholesterol, high LDL cholesterol, arterial problems and age at nilotinib initiation. ABI failed in detecting authentified arterial problems detected by other means. The Pearson correlation test nearly reached statistical significance between nilotinib duration and arterial problems (p=0.07).In conclusion, nilotinib induces clear metabolic disturbances along treatment, particularly for lipids and glucose parameters, which can be responsible for significant arteriopathies, that ABI failed to detect. These results should promote the lipids and glucose parameters follow-up during CML treatment by nilotinib in order to detect disturbances at early times, correct them using strict dietary rules and/or concomitant medications to avoid arterial problems at later time points. Disclosures:Nicolini:Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (review of Technology Appraisal No. 90): a systematic review and economic analysis

Occlusive vascular events such as myocardial infarction (MI), ischaemic stroke and transient ischaemic attack (TIA) are the result of a reduction in blood flow associated with an artery becoming narrow or blocked through atherosclerosis and atherothrombosis. Peripheral arterial disease is the result of narrowing of the arteries that supply blood to the muscles and other tissues, usually in the lower extremities. The primary objective in the treatment of all patients with a history of occlusive vascular events and peripheral arterial disease is to prevent the occurrence of new occlusive vascular events. To assess the clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole (MRD) alone or with aspirin (ASA) compared with ASA (and each other where appropriate) in the prevention of occlusive vascular events in patients with a history of MI, ischaemic stroke/TIA or established peripheral arterial disease. To consider the clinical effectiveness and cost-effectiveness of clopidogrel in patients with multivascular disease. This review is an update of the evidence base for the National Institute for Health and Clinical Excellence (NICE) guidance Technology Appraisal No. 90 (TA90) entitled Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (2005). Four electronic databases (EMBASE, MEDLINE, Web of Science and The Cochrane Library) were searched for randomised controlled trials (RCTs) and economic evaluations. Submissions to NICE by the manufacturers of the interventions were also considered. A systematic review of clinical effectiveness and cost-effectiveness was conducted. To manage heterogeneity between trials, indirect analysis (using a mixed-treatment methodology) was performed on selected clinical outcomes. A new economic model was developed to assess incremental costs per life-year gained [quality-adjusted life-years (QALYs)]. For evidence of clinical effectiveness, four RCTs were identified: CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events), ESPRIT (European/Australasian Stroke Prevention in Reversible Ischaemia Trial), PRoFESS (Prevention Regimen For Effectively avoiding Second Strokes) and ESPS-2 (Second European Stroke Prevention Study). In CAPRIE (patients with MI, ischaemic stroke or peripheral arterial disease), statistically significant outcomes in favour of clopidogrel were noted for the primary outcome (first occurrence of ischaemic stroke, MI or vascular death) compared with ASA [relative risk reduction 8.7%; 95% confidence interval (CI) 0.3% to 16.5%; p = 0.043]. In ESPRIT (patients with ischaemic stroke/TIA) for the primary outcome (first occurrence of death from all vascular causes, non-fatal stroke, non-fatal MI or major bleeding complication), the risk of event occurrence was statistically significantly lower in the MRD + ASA arm than in the ASA arm [hazard ratio (HR) 0.80; 95% CI 0.66 to 0.98], with no statistically significant difference in bleeding events between the two arms. In PRoFESS (patients with ischaemic stroke) the rate of recurrent stroke of any type (primary outcome) was similar in the MRD + ASA and clopidogrel groups, and the null hypothesis (that MRD + ASA was inferior to clopidogrel) could not be rejected. In ESPS-2 (patients with ischaemic stroke/TIA), on the primary outcome of stroke, statistically significant differences in favour of MRD + ASA were observed compared with ASA and MRD alone (relative risk 0.76; 95% CI 0.63 to 0.93). The outcomes addressed in the mixed-treatment comparisons (limited by the available data) for the ischaemic stroke/TIA population confirmed the results of the direct comparisons. The 11 economic evaluations included in the review of cost-effectiveness indicated that for patients with previous peripheral arterial disease, ischaemic stroke or MI, clopidogrel is cost-effective compared with ASA, and for patients with previous ischaemic stroke/TIA, treatment with MRD + ASA is cost-effective compared with any other treatment in patients in the secondary prevention of occlusive vascular events. The relevance of the review was limited as the economic evaluations were not based on the most current clinical data. Cost-effectiveness results generated from the Assessment Group's de novo economic model suggested that the most cost-effective approach for patients with ischaemic stroke/TIA is clopidogrel followed by MRD + ASA then ASA. For patients with MI, the most cost-effective approach is ASA followed by clopidogrel. For patients with established peripheral arterial disease, the most cost-effective approach is clopidogrel followed by ASA. For patients with multivascular disease, clopidogrel followed by ASA is the most cost-effective approach. Incremental cost-effectiveness ratios (ICERs) were also calculated for patients who are intolerant to ASA. Assuming that the branded price for clopidogrel is used and TA90 guidance is not applied, all of the ICERs range between £2189 and £13,558 per QALY gained. Probabilistic sensitivity analyses were fully consistent with these findings. The evidence suggests that the most cost-effective treatment for patients with ischaemic stroke/TIA is clopidogrel followed by MRD + ASA followed by ASA; for patients with MI, ASA followed by clopidogrel; and for patients with established peripheral arterial disease or multivascular disease, clopidogrel followed by ASA. The National Institute for Health Research Health Technology Assessment programme.

Impact of Clinical and Subclinical Peripheral Arterial Disease in Mid-Term Prognosis of Patients With Acute Coronary Syndrome

Observational studies report poor prognosis of patients after acute coronary syndrome (ACS) in the presence of previous peripheral arterial disease (PAD), but data on subclinical PAD are scarce. This study was designed to assess the predictive value of clinical and subclinical PAD in the follow-up of patients after an ACS. We included 1,054 patients hospitalized for an ACS who survived the acute phase. Patients were divided into 3 groups: clinical PAD (previously diagnosed PAD or intermittent claudication), subclinical PAD (defined as ankle-brachial index <or=0.9 or >1.4), and no PAD. Clinical PAD was present in 150 patients (14.2%) and 298 cases of subclinical PAD were detected (28.3%). Patients with PAD (clinical and subclinical PAD) were significantly older and had a higher prevalence of hypertension and diabetes mellitus than those without PAD. During the 1-year follow-up, 59 patients died (5.6%). Previous PAD (hazard ratio 4.38, 95% confidence interval 1.96 to 9.82, p <0.001) and subclinical PAD (hazard ratio 2.35, 95% confidence interval 1.05 to 5.23, p <0.05) were associated with increased cardiovascular mortality. Moreover, patients with clinical PAD had higher rates of major cardiovascular events (myocardial infarction, angina, and heart failure) than patients with subclinical PAD or without PAD. In conclusion, beyond clinical PAD, measurement of ankle-brachial index after ACS provides substantial information on intermediate-term prognosis.

Impact of Prior Peripheral Arterial Disease and Stroke on Outcomes of Acute Coronary Syndromes and Effect of Evidence-Based Therapies (from the Global Registry of Acute Coronary Events)

We assessed the effect of previous peripheral arterial disease (PAD) and stroke on clinical outcomes in patients with acute coronary syndrome (ACS) and sought to ascertain the effectiveness of evidence-based therapies in these patients. We used data from the multinational Global Registry of Acute Coronary Events. Patients were enrolled at 102 hospitals in 13 countries between April 1999 and September 2005. Patients presenting with ACS were stratified according to the presence of previous PAD, stroke, PAD and stroke, or neither. In-hospital analysis included 48,418 patients and 6-month analysis included 32,735 patients. The primary end point was all-cause mortality and major adverse cardiac events during 6-month follow-up. Adverse in-hospital and 6-month events were lowest in patients with neither PAD nor stroke and highest in patients with PAD and stroke after adjustment for baseline demographics and co-morbidities. In-hospital mortality for the 4 groups (neither, PAD, stroke, PAD and stroke) was 4.5% versus 7.2% versus 8.9% versus 9.4% (p <0.001) and that for 6-month mortality was 3.9% versus 8.8% versus 9.3% versus 12%, and these differences persisted after accounting for differences in baseline characteristics. Use of evidence-based therapies was associated with significantly less morbidity and mortality in all ACS subgroups. In conclusion, outcomes after ACS are worse in patients with PAD or stroke, with the highest risk in patients with the 2 conditions and the use of evidence-based therapies are associated with improved outcomes in all ACS subgroups.