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San Raffaele Cimena, Italy

Quintavalle C.,CNR Institute of Neuroscience | Fiore D.,CNR Institute of Neuroscience | Donnarumma E.,Fondazione IRCCS SDN | Bianco A.,University of Naples Federico II | And 4 more authors.
Circulation | Year: 2012

BACKGROUND-: The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial. METHODS AND RESULTS-: First, we investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg within 24 hours before contrast media [CM] exposure; n=202) or (2) the control group (n=208). All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution. Second, we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase >10% of serum cystatin C concentration within 24 hours after CM exposure) occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208 patients in the control group (17.8%) (P=0.005; odds ratio=0.22; 95% confidence interval, 0.07-0.69). CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease (estimated glomerular filtration rate, 31-60 mL/min per 1.73 m). In the in vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and (2) restored the survival signals (mediated by Akt and ERK pathways). CONCLUSIONS-: A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI. This beneficial effect is observed only in patients at low to medium risk. © 2012 American Heart Association, Inc. Source

Briguori C.,Laboratory of Interventional Cardiology | Quintavalle C.,CNR Institute of Neuroscience | De Micco F.,IRCCS MultiMedica | Condorelli G.,Fondazione SDN
Archives of Toxicology | Year: 2011

Contrast-induced acute kidney injury (CI-AKI) accounts for approximately 10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay, and represents a powerful predictor of poor early and late outcome. N-acetylcysteine (NAC) is a thiol compound classically known as a mucolytic agent, which is a potent antioxidant that scavenges a wide variety of oxygen-derived-free-radicals and may be capable of preventing acute kidney injury. In the present study, we will review (1) the pathophysiology of the CI-AKI and (2) the experimental and clinical data on the effects of NAC in preventing CI-AKI. © 2010 Springer-Verlag. Source

Mureddu G.F.,Dell | Brandimarte F.,San Giovanni Addolorata Community Hospital | De Luca L.,Laboratory of Interventional Cardiology
Journal of Cardiovascular Medicine | Year: 2012

High-density lipoprotein cholesterol (HDL-C) is a strong and independent predictor of major cardiovascular events in a wide range of patients. The relationship between HDL-C cholesterol and cardiovascular risk appears to be linear, continuous, negative and independent of other risk factors such as blood pressure, smoking and BMI. In addition, the inverse relationship between HDL-C and cardiovascular events does not depend on low-density lipoprotein cholesterol (LDL-C) levels, so a substantial residual cardiovascular risk is maintained also in individuals with LDL-C levels below the target recommended by scientific guidelines. Furthermore, a strong relationship among HDL-C levels, progression of atherosclerosis and risk of cardiovascular diseases has been also demonstrated. Treatments that increase HDL-C levels have been shown to be effective in reducing incidence of cardiovascular diseases both in primary and secondary prevention settings. However, proof that increasing HDL-C levels by pharmacological treatment is able to confer a reduction in major cardiovascular outcomes independent of changes in LDL-C or triglycerides levels is not completely defined. Among currently available compounds, statins do not seems to have a sufficient effect on HDL-C profile. Studies on fibrates have shown inconclusive results. Although niacin has been demonstrated to reduce the incidence of major cardiovascular events paralleling the regression of atherosclerosis, significant side-effects still limit its use. The potential benefit of cholesterol ester transfer protein inhibition is still under investigation. The combination therapy of fibrates with statins is also controversial. Thus, despite the potentially favorable effect of raising HDL-C levels, the available guidelines still do not consider HDL-C levels as a specific target for therapy. Further studies are needed to assess the role of new compounds to raise HDL-C levels or modify HDL composition and functionality. © 2012 Italian Federation of Cardiology. Source

Rubboli A.,Laboratory of Interventional Cardiology | Oldgren J.,Uppsala University | Marin F.,Hospital Universitario Virgen Of La Arrixaca | Lip G.,University of Birmingham
Internal and Emergency Medicine | Year: 2013

Effective secondary prevention after acute coronary syndrome (ACS) is largely dependent on dual antiplatelet therapy (DAPT). Despite DAPT, however, patients remain at substantial risk of major adverse cardiovascular events (i.e., cardiovascular death, myocardial infarction, stroke), and, therefore, combination therapy of oral anticoagulant and antiplatelets has been previously proposed. Because of the increase in bleeding and the cumbersome management of vitamin K antagonists, such combination therapy has never gained much popularity. The recent development of new, non vitamin K antagonists, direct oral anticoagulants (NOACs), including dabigatran, apixaban, rivaroxaban, and darexaban, which have more favorable pharmacokinetics and pharmacodynamics, as well as higher safety, has renewed the interest on combination therapy. Whereas phase II trials with dabigatran, apixaban, rivaroxaban, and darexaban have consistently shown an increased bleeding risk with combination therapy, a potential increased efficacy has emerged for apixaban and rivaroxaban, thereby prompting phase III studies. Both APPRAISE-2 and ATLAS ACS 2-TIMI 51 trials confirm a dose-dependent increase in major bleeding events, including intracranial, with apixaban and rivaroxaban when combined with DAPT. Low-dose (2.5 mg twice daily) rivaroxaban on the other hand, is associated with a significantly higher efficacy on the occurrence of combined cardiovascular death, myocardial infarction, stroke, and of stent thrombosis. Owing to the persistent uncertainty regarding the net clinical benefit of combined therapy of NOAC, namely low-dose (2.5 mg twice daily) rivaroxaban and DAPT of aspirin and clopidogrel, further studies are warranted to identify the ACS patient who will benefit most from such treatment, also in comparison to the current therapeutic standard represented by DAPT of aspirin and ticagrelor (or prasugrel). © 2013 SIMI. Source

Rubboli A.,Laboratory of Interventional Cardiology
Current Medical Research and Opinion | Year: 2015

Once daily dosing schedule is associated with increased adherence to and persistence with cardiovascular therapies. Such feature has been claimed responsible for the significantly lower (both temporary and permanent) discontinuation of oral anticoagulation with rivaroxaban (which is given once daily) compared to dabigatran (which is given twice daily) in a large, real-world dataset of patients with atrial fibrillation (AF) in the United States. While a cause-effect relationship between dosing schedule and adherence and persistence could not be established, the above finding supports nonetheless the preferential selection of the non vitamin-K-antagonists oral anticoagulant (NOAC) with the easiest and most convenient regimen. Given however, the differences in efficacy and safety observed with the various NOACs compared to warfarin in the phase III clinical trials in non-valvular AF, careful individualization of treatment should be pursued, being dosing schedule only one of the variables to be taken into account. Maximal effort instead, should be put in implementing measures to enhance patient's adherence to and persistence with treatment. © 2015 Taylor & Francis. Source

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