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Fondaparinux was inferior to UFH in the setting of primary PCI in patients with STEMI (OASIS-6 trial) [ 256 ].

Bleeding contributes to worse outcome and can be prevented by implementing the following measures:

formally assess and document bleeding risk in every patient;

avoid crossover between UFH and LMWH;

adjust antithrombotic therapy doses based on weight and renal function ( Table 37

Table 37
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Recommendations of antithrombotic drug use in chronic kidney disease

Table 37
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Recommendations of antithrombotic drug use in chronic kidney disease

use radial access in patients at high risk of bleeding;

stop anticoagulation after PCI unless a specific indication exists;

adopt selective downstream use of GPIIb-IIIa inhibitors, as required in the catheterization laboratory, in preference to unselective upstream use.

1 month after BMS implantation in stable angina [ 55 , 60 , 94 ];

6–12 months after DES implantation in all patients [ 60 , 94 ];

1 year in all patients after ACS, irrespective of revascularization strategy.

Data suggest that certain patient populations (e.g. high risk for thromboembolic events, patients after SES or PES implantation), may benefit from prolonged DAPT beyond 1 year. The downside of this strategy is the increased rate of severe bleeding complications over time. Recent data suggest that DAPT for 6 months might be sufficient because late and very late stent thrombosis correlate poorly with discontinuation of DAPT.

Indications for DAPT and treatment duration depend primarily on the clinical indication (stable CAD, NSTE-ACS, STEMI), irrespective of the mode of revascularization. Secondary prevention demands lifelong antiplatelet therapy with 75–325 mg ASA daily (Section 13).

Antiplatelet agents also promote long-term graft patency, especially SVG. In cases of aspirin intolerance, clopidogrel should be used. There are no RCTs comparing the efficacy of clopidogrel or clopidogrel plus aspirin vs. aspirin alone on long-term graft patency.

Triple therapy consisting of ASA, clopidogrel (or prasugrel), and a vitamin K antagonist should only be given if a compelling indication exists, i.e. paroxysmal, persistent, or permanent AF with CHADS 2 score ≥ 2, mechanical valves, recent or recurrent history of deep venous thrombosis, or pulmonary embolism. Triple therapy should only be prescribed for the shortest necessary duration with frequent INR measurement (target INR 2–2.5) [ 257 ]. In patients with a compelling indication for long-term anticoagulation, BMS implantation or stand-alone balloon angioplasty or CABG should be preferred over DES to restrict the duration of triple therapy to 1 month.

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Cardioprotective effects of nanoemulsions loaded with natural anti-inflammatory bioactives against doxorubicin-induced cardiotoxicity in rat cardiomyocytes.

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Abstract No: e24227

Citation: J Clin Oncol 36, 2018 (suppl; abstr e24227)

Author(s): Vincenzo Quagliariello, Raffaele Vecchione, Chiara Di Cicco, Alberta De Capua, Carmela Coppola, Giovanna Piscopo, Fabrizio Maurea, Rolando Paciello, Rosario Vincenz Iaffaioli, Paolo Netti, Nicola Maurea; Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy; Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, Italy; Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”- IRCCS, Naples, Division of Cardiology, Naples, Italy; INT PASCALE, Naples, Italy; Department of Colorectal Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale, IRCCS, Napoli, Italy

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Abstract:

Background: Doxorubicin is a highly active antineoplastic agent; however, its clinical use is limited due to associated cardiotoxicity. This study was performed to evaluate the beneficial effects of bioavailable nanoemulsions loaded with lycopene or curcumin, both natural molecules with anti-inflammatory and vascular protective properties, against doxorubicin-induced cardiotoxicity in rat cardiomyocytes Methods: Nanoemulsions were produced by using a high-pressure homogenizer. H9C2 cells were incubated with lycopene or curcumin loaded nanoemulsions at different concentrations ranging from 0,05 up to 2% oil alone or in combination with Doxorubicin at 200 nM. Cell viability was evaluated by using a modified MTT method. The levels of lipid peroxidation products (MDA and 4-HNA), interleukins involved in cardiotoxicity (IL-6, IL-8, IL-1β), IL-10, tumour necrosis factor-alpha (TNF-α), nitric oxide (NO) were analyzed using ELISA method. Results: Nanoemulsions loaded with both bioactives showed a nanometric and homogeneous dimension in time with an overall hydrodynamic size of around 100 nm. A marked cell viability enhancement of around 35-40 % compared to only Doxorubicin-treated cells (p < 0,01) and significant reduction of lipid peroxidation (MDA and 4-HNA) in cardiomyocytes pretreated with both nanoemulsions in combination with doxorubicin. Moreover, both nanoemulsions ameliorated the cardiomyocytes release of IL-6, IL-8, IL-1β, TNF-α and NO of around 37 and 53 %, respectively and increased IL-10 production of 40-47 % compared to un-pretreated cells (p < 0,05 for all) indicating anti-inflammatory properties. Conclusions: This study demonstrates for the first time the cardioprotective effects of lycopene and curcumin loaded nanoemulsions against doxorubicin -induced cardiotoxicity. Collectively, these data indicate that pretreatment of cardiomyocytes with nanoemulsions alleviates doxorubicin-induced cardiotoxicity via reducing oxidative lipid damage, NO and cytokines release. This results places interesting initial biological evidences for subsequent cardioprotection studies in preclinical models.

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