Improving Adherence to Ticagrelor in Patients After Acute Coronary Syndrome: Results from the PROGRESS Trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor is recommended for at least 12 months in patients after an acute coronary syndrome (ACS). However, its underuse and premature discontinuation are common in clinical practice. We aimed to investigate the impact of a dedicated follow-up strategy with clinical visits and counselling on adherence levels to ticagrelor in patients after ACS. METHODS: PROGRESS (PROmotinG dual antiplatelet therapy adheREnce in the setting of acute coronary Syndromes) is a prospective, randomized trial enrolling 400 ACS patients treated with ticagrelor. Patients were randomized to be followed-up in a dedicated outpatient clinic (In-person follow-up group, [IN-FU], n=200), or with scheduled for phone interviews only (Telephone follow-up group [TEL-FU], n=200), to assess ticagrelor adherence and related complications. DAPT disruption was defined as an interruption of the administration of the drug due to complications or other reasons of non-adherence, and divided according to the duration into short (1-5 days), temporary (6-30 days) and permanent (≥30 days) disruption. The primary endpoint was the rate of DAPT disruption at 1-year follow-up. RESULTS: The rate of ticagrelor disruption at 1 year follow-up was higher in the TEL-FU group than in the IN-FU group (19.6 vs 5.5%; p<0.0001). The IN-FU group reported a significantly lower rate of short (3.0 vs 8.5%; p=0.012) and permanent (2.0 vs 9.6%; p=0.012) disruption than TEL-FU group. The rate of major bleeding did not differ significantly between the 2 groups (p=0.450). CONCLUSION: The PROGRESS trial showed a net reduction in DAPT disruption in patients followed-up with clinical (in-person) follow-up visits in a dedicated outpatient clinic compared with those scheduled for phone interviews only.

Transradial access versus transfemoral access: a comparison of outcomes and efficacy in reducing hemorrhagic events.

Introduction: The radial artery is currently the most widely used access site for PCI procedures both acute and stable patient settings. Thanks to advantages in pharmacological therapy as well as in interventional devices, the rate of ischemic complications following PCI has significantly decreased. Nevertheless, this has been counterbalanced by an increased risk of periprocedural and late bleeding event, that can occur both at access and non-access sites. Choice of access site for PCI is of paramount importance to reduce the risk of access-related bleeding events. Areas covered: The aim of this review is to provide an overview of the actual available evidence comparing the transradial versus transfemoral approach to reduce hemorrhagic events. The most robust evidence comes from large randomized trials, partly also from observational registries, which compared the transradial and transfemoral approach. Expert opinion: Results show that radial access has proved to be decisive in reducing the incidence of hemorrhagic events. Furthermore, it showed a significant reduction in mortality and AKI compared to transfemoral access. However, increased experience in the use of the radial approach has led to less practice in the use of the femoral approach, which may be useful in cases of emergency, complications or inability to use the radial artery.

Lomitapide in homozygous familial hypercholesterolemia: cardiology perspective from a single-center experience.

AIMS: Homozygous familial hypercholesterolemia (HoFH) is a genetic dyslipidemia characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerosis. Frequently, traditional lipid-lowering therapy is ineffective in these patients, and lipoprotein apheresis is required. Lomitapide has been recently approved for HoFH. We reported our experience in HoFH patients treated with lomitapide, evaluating its efficacy and safety profile. METHODS: Probands suspected for familial hypercholesterolemia were extrapolated from the registry of patients admitted to our cardiology department. Dutch Lipid Clinic Network (DLCN) criteria were adopted to diagnose familial hypercholesterolemia clinically. Individuals receiving a definite or probable diagnosis of familial hypercholesterolemia underwent family cascade screening and genetic test. Patients with a genetic diagnosis of HoFH were treated with lomitapide and monitored with serial follow-up visits. RESULTS: Within 1 year of screening, from a population of 3250 patients admitted to our cardiology department, seven probands were selected with a DLCN score greater than 5. A total of two patients resulted genetically homozygotes for familial hypercholesterolemia and started lomitapide. A marked reduction in LDL-C occurred in both patients on lomitapide (78% reduction in patient 1 and 86% in patient 2 already on lipoprotein apheresis, compared with baseline LDL-C), allowing the apheresis treatment to be stopped in the second case. Lomitapide was well tolerated, and both patients experienced only mild gastrointestinal events. CONCLUSION: Lomitapide is an effective and well tolerated cholesterol-lowering drug approved for the treatment of HoFH patients. It would be useful to administer it early in these patients to reduce LDL-C and avoid the development of fatal cardiovascular complications.

Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement.

von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy.

Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions. Moreover, VWF and ADAMTS13 have been recently proposed as prognostic biomarkers in cardiovascular, metabolic, and inflammatory diseases, such as diabetes, stroke, myocardial infarction, and sepsis. All these features make VWF an attractive therapeutic target in thromboinflammation. Several lines of research have recently investigated "tailor-made" inhibitors of VWF. Results from animal models and clinical studies support the potent anti-inflammatory and antithrombotic effect of VWF antagonism, providing reassuring data on its safety profile. This review describes the role of VWF in vascular inflammation "from bench to bedside" and provides an updated overview of the drugs that can directly interfere with the VWF/ADAMTS13 axis.

Cardiovascular calcification and subcortical bone demineralization in hypertension.

The present study investigated cardiovascular calcification, peripheral bone mineral density (BMD), and lab indices in hypertensive patients aged 55-74 years without severe kidney dysfunction. Cardiovascular calcification was investigated by ultrasound examinations at eight sites: aortic valve, left and right common carotid artery, left and right carotid artery bifurcation, left and right internal carotid artery, and abdominal aorta. The presence/absence of calcification at each site was coded as 1/0, respectively, for the calculation of a cumulative score. Peripheral bone mineral density was assessed by forearm quantitative computed tomography (pQCT) and was defined as low if the T-score was <-1. Lab work-up included plasma creatinine, calcium, phosphorus, parathyroid hormone and 25-(OH) vitamin D measurements. Ninety-one patients were studied. The range was 2-8 for the calcification score and 229-492 mg cm-3 for bone mineral density. The prevalence of low bone densitometry was 83.5%. The calcification score and bone densitometry were inversely correlated in a non-adjusted analysis (R=-0.297, P=0.004) and in multivariable regression (beta=-0.335, P=0.003). The association was significant for subcortical bone (beta=-0.302, P=0.007) but not for cortical bone or trabecular bone (P⩾0.194 in both cases). The calcification score was associated with a low prevalence of bone densitometry in the non-adjusted analysis (odds ratio=2.53, 95% CI=1.41/4.54, P=0.002) and in the multivariable logistic regression (odds ratio=2.46, 95% CI=1.25/4.81, P=0.009). Cardiovascular calcification was independently associated with peripheral bone densitometry in hypertensive patients. The data support the hypothesis that vascular calcification and low bone densitometry share some determinants in hypertensive patients.

Rapid ultrasound score as an indicator of atherosclerosis' clinical manifestations in a population of hypertensives: the interrelationship between flow-mediated dilatation of brachial artery, carotid intima thickness, renal resistive index and retina resistive index of central artery.

OBJECTIVE: Flow-mediated dilatation (FMD) of brachial artery, renal resistive index (RRI), retina resistive index of central artery (RRICA) and carotid intima-media thickness (IMT) have been used for ultrasound assessment of cardiovascular risk as good surrogate markers of pre-clinical atherosclerosis. We investigated the interrelationship of these four parameters and examined whether an integrated score is a good indicator of atherosclerotic disease in hypertensives. METHODS: One-hundred fifty-two consecutive subjects were enrolled in this study between April 2004 and April 2005. Each patient underwent cerebral computed tomography, coronarography, carotid, renal, central retinal and femoral arteries Doppler ultrasonographic evaluation. Statistical analysis was performed using ANOVA, Fisher test, Pearson correlation and stepwise regression analyses. RESULTS: FMD, RRICA, IMT and RRI were significantly correlated with each other. In multiple regression analysis age, pulse pressure, hypertension duration were independently related with the four parameters. Eighty-one findings of total atherosclerotic disease (ADAD were recorded overall (15 cerebrovascular disease, 20 coronary heart disease or myocardial infarction, 22 carotid plaques and 24 low limb plaques). Using an integrated score we were able to divide the population into three scoring bands. In the lowest band we classified 87 patients with 16% of total AD; in the intermediate 40 patients with 30% of total AD, in the highest 25 patients with 54% of total AD. Differences between groups were significant (p<0.05). CONCLUSION: A potential benefit of these integrated, low-cost and easy-to-detect parameters, is the stratification of patients with atherosclerotic risk. This method may prove useful in discovering those with atherosclerosis in a pre-clinical stage for whom therapy initiated before complications could reduce the risk for a cerebro-cardio-vascular event.