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In a randomized trial involving patients with high-risk vascular disease, the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers but was not associated with a lower rate of cardiovascular events than placebo. Pharmacologic reduction of the low-density lipoprotein (LDL) cholesterol level with statins substantially decreases the risks of death and complications from cardiovascular causes. 1 , 2 Considerable interest has focused on the identification of approaches that might further reduce cardiovascular-event rates among high-risk patients. 3 Epidemiologic studies have shown inverse associations between high-density lipoprotein (HDL) cholesterol levels and cardiovascular outcomes, 4 – 6 a correlation that persists despite treatment with statins. 7 Nevertheless, therapeutic interventions that raise the HDL cholesterol level have not been shown to reduce cardiovascular risk. Cholesteryl ester transfer protein (CETP) modulates the transfer of esterified cholesterol from HDL to apolipoprotein B–containing lipoproteins. 8 Two . . .

Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease. ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years. ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.

The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations. SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score ≥33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972. SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (pinteraction 0·0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (pinteraction 0·67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0·725 and for external (DELTA registry) validation of 0·716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0·567 and 0·612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI. Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score. Boston Scientific Corporation.

In an effort to reduce the rate of sickle cell crises and acute chest syndrome, a trial compared prasugrel with placebo in patients 2 through 17 years of age who had sickle cell anemia. Prasugrel did not have a significant effect on the rate of vaso-occlusive crises. Sickle cell anemia, which is estimated to affect 100 million persons worldwide, is an inherited blood disorder characterized by hemolytic anemia and recurrent vaso-occlusive crises that are associated with hospitalizations, impaired quality of life, and early death. 1 – 3 The pathophysiological mechanism of vaso-occlusion in sickle cell anemia is complex. The polymerization of sickle hemoglobin initiates a cascade of thrombotic and inflammatory insults that result in progressive vascular damage and ischemic end-organ injury. 4 Hydroxyurea is partially effective in reducing the frequency of acute vaso-occlusive events, but it has not been shown to prevent organ damage. 5 There is an unmet need for . . .

Peripheral artery disease (PAD), which comprises atherosclerosis of the abdominal aorta, iliac, and lower-extremity arteries, is underdiagnosed, undertreated, and poorly understood by the medical community. Patients with PAD may experience a multitude of problems, such as claudication, ischemic rest pain, ischemic ulcerations, repeated hospitalizations, revascularizations, and limb loss. This may lead to a poor quality of life and a high rate of depression. From the standpoint of the limb, the prognosis of patients with PAD is favorable in that the claudication remains stable in 70% to 80% of patients over a 10-year period. However, the rate of myocardial infarction, stroke, and cardiovascular death in patients with both symptomatic and asymptomatic PAD is markedly increased. The ankle brachial index is an excellent screening test for the presence of PAD. Imaging studies (duplex ultrasonography, computed tomographic angiography, magnetic resonance angiography, catheter-based angiography) may provide additional anatomic information if revascularization is planned. The goals of therapy are to improve symptoms and thus quality of life and to decrease the cardiovascular event rate (myocardial infarction, stroke, cardiovascular death). The former is accomplished by establishing a supervised exercise program and administering cilostazol or performing a revascularization procedure if medical therapy is ineffective. A comprehensive program of cardiovascular risk modification (discontinuation of tobacco use and control of lipids, blood pressure, and diabetes) will help to prevent the latter.

Hydroxyurea increases expression of fetal hemoglobin and decreases clinical complications in children with sickle cell anemia. A trial of a higher dose (30 mg per kg per day) as compared with a standard dose (20 mg per kg) in children in sub-Saharan Africa showed improved outcomes without increased toxicity.

Implantation of stainless-steel stents for disease of the superficial femoral artery has been associated with high rates of late clinical failure, and balloon angioplasty is therefore the preferred procedure. In this randomized trial, the use of nitinol stents was associated with lower rates of restenosis and better treadmill exercise performance at 6 months and 12 months than was the use of balloon angioplasty. The use of nitinol stents was associated with lower rates of restenosis and better treadmill exercise performance at 6 months and 12 months than was the use of balloon angioplasty. The use of percutaneous transluminal angioplasty to revascularize the superficial femoral artery can result in initial technical success rates of more than 95 percent, with a low risk of complications. 1 However, late clinical failure remains an important concern. Restenosis occurs in 40 to 60 percent of treated segments after one year. 1 – 3 The use of angioplasty to treat extensive disease of the superficial femoral artery has particularly poor results: at one year, the rates of restenosis exceed 70 percent for lesions longer than 100 mm. 4 Endovascular stenting avoids the problems of early elastic recoil, residual stenosis, and flow-limiting dissection after . . .

Background Worldwide, at least 200 million people are affected by peripheral vascular diseases (PVDs), including peripheral arterial disease (PAD), chronic venous insufficiency (CVI) and deep vein thrombosis (DVT). The high prevalence and serious consequences of PVDs have led to the development of several diagnostic tools and clinical guidelines to assist timely diagnosis and patient management. Given the increasing number of diagnostic methods available, a comprehensive review of available technologies is timely in order to understand their limitations and direct future development effort. Main body This paper reviews the available diagnostic methods for PAD, CVI, and DVT with a focus on non-invasive modalities. Each method is critically evaluated in terms of sensitivity, specificity, accuracy, ease of use, procedure time duration, and training requirements where applicable. Conclusion This review emphasizes the limitations of existing methods, highlighting a latent need for the development of new non-invasive, efficient diagnostic methods. Some newly emerging technologies are identified, in particular wearable sensors, which demonstrate considerable potential to address the need for simple, cost-effective, accurate and timely diagnosis of PVDs.

Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age ≥ 18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or ≥2 of the following: age ≥ 65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365 days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.

Purpose This study was designed to assess the effect of calcium on the efficacy of DEB during revascularization of steno-obstructive SFA lesions. Methods Sixty patients with de novo lesions of the superficial femoral artery underwent endovascular treatment with drug eluting balloons (DEB). DEB was selected according to vessel reference diameter (1:1). In case of residual stenosis > 50 % or flow-limiting dissection, postdilatation with conventional balloon or provisional stenting was done. Patients were classified into eight groups according to circumferential distribution of calcium on CT-angiography axial images (from 0° to 360°) and to its length (length < or > 3 cm) evaluated with digital-subtraction-angiography. Ankle-brachial index (ABI), late lumen loss (LLL), target lesion revascularization (TLR), primary (PP) and secondary (SP) patency, major adverse events (MAE), and Rutherford shift were evaluated at 1-year follow-up and correlated with the amount of calcium. Results Revascularization was successful in all cases. Flow-limiting dissection occurred in five cases (8.3 %) with a higher circumferential degree of calcium and solved in three cases with postdilatation and in the other two with provisional stenting. DEB effect was lower in patients with higher degree of calcium (>270° vs. <90°): ABI 0.71 ± 0.07 versus 0.92 ± 0.07; LLL 0.75 ± 0.21 versus 0.45 ± 0.1; PP 50 versus 100 %; SP 50 versus 100 %; TLR 25 versus 0 %; MAE 25 versus 0 %. Conclusions Calcium represents a barrier to optimal drug absorption. Circumferential distribution seems to be the most influencing factor with the worst effect noticed in 360° calcium presence.