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Lucia Barbieri, Monica Verdoia, Alon Schaffer, Harry Suryapranata, Giuseppe De Luca
BACKGROUND: Patients with coronary artery disease who undergo stent implantation and have concomitant indication for long-term oral anticoagulation represent a considerable proportion of the overall population. To date there is still no consensus about the optimal antithrombotic strategy to choose in this kind of patients, due to the difficult balance between an increased risk of bleeding and thromboembolic complications. Therefore, the aim of this study was to perform a meta-analysis to evaluate the risk and benefits of triple antithrombotic therapy versus dual antithrombotic therapy in patients undergoing coronary stent implantation, requiring long-term oral anticoagulation...
October 18, 2016: Cardiovascular Drugs and Therapy
Edem Efe, Ibrahim Kocayiğit, Pabuccu Mustafa Türker, Küçükukur Murat, Alpaslan Erkan, Taş Sedat, Çil Alper, Aksoy Murat Necati, Vural Mustafa Gökhan, Akdeniz Bahri
OBJECTIVES: Dual antiplatelet therapy (DAPT), consisting of clopidogrel and aspirin, is the main-stay treatment of acute coronary syndromes (ACS). However, major adverse cardiovascular events may occur even in patients undergoing DAPT, and this has been related to the variable pharmacodynamic efficacy of these drugs, especially clopidogrel. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are novel inflammatory markers for cardiovascular risk stratification, which may reflect an inflammatory state and thus high on-treatment platelet reactivity (HPR)...
July 2016: Indian Journal of Pharmacology
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
Javier A Valle, Laura Graham, Aerin DeRussy, Kamal Itani, Mary T Hawn, Thomas M Maddox
BACKGROUND: Triple therapy, or the use of anticoagulants with dual antiplatelet therapy (DAPT), is often used to protect against ischemic events in post-percutaneous coronary intervention (PCI) patients with indications for anticoagulation, but is associated with increased bleeding. As both ischemic and bleeding risks increase in the perioperative period, the impact of triple therapy may be especially pronounced in patients undergoing surgery. Outcomes in this population are currently unknown...
October 12, 2016: World Journal of Surgery
Francesco Pelliccia, Fabiana Rollini, Giuseppe Marazzi, Cesare Greco, Carlo Gaudio, Dominick J Angiolillo, Giuseppe Rosano
The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI)...
October 3, 2016: International Journal of Cardiology
Gian Marco Rosa, Daniele Bianco, Alberto Valbusa, Laura Massobrio, Francesco Chiarella, Claudio Brunelli
After acute coronary syndromes (ACS), the so-called dual antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in combination with a thienopyridine (clopidogrel, prasugrel) or with a cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events. Ticagrelor, un particular, is an effective drug as it isn' a prodrug, doesn't require metabolic activation and demonstrates a rapid onset and faster offset of action. Areas covered: This article evaluates the pharmacokinetics, efficacy, safety and tolerability of ticagrelor during DAPT after ACS and its potential use beyond the canonical twelve months after PCI...
October 7, 2016: Expert Opinion on Drug Metabolism & Toxicology
Ashan Gunarathne, Shahana Hussain, Anthony H Gershlick
Dual antiplatelet therapy (DAPT) with aspirin combined with either a thienopyridine (clopidogrel or prasugrel) or acyclopentyl-triazolo-pyrimidine (ticagrelor) plays a vital role in the management of acute coronary syndrome (ACS) especially in those undergoing percutaneous coronary intervention (PCI) but even those being managed medically. Observational studies and some formal studies have shown patients on the standard dual antiplatelet regimen (clopidogrel and aspirin) continue to have further ischemic events and can suffer stent thrombosis...
October 4, 2016: Expert Review of Cardiovascular Therapy
Lisa M Greene, Seema M Nathwani, Daniela M Zisterer
T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematopoietic malignancy prone to relapse and drug resistance. Half of all T-ALL patients exhibit mutations in Notch1, which leads to aberrant Notch1 associated signaling cascades. Notch1 activation is mediated by the γ-secretase cleavage of the Notch1 receptor into the active intracellular domain of Notch1 (NCID). Clinical trials of γ-secretase small molecule inhibitors (GSIs) as single agents for the treatment of T-ALL have been unsuccessful...
October 2016: Oncology Letters
Daisuke Ueshima, Takashi Ashikaga, Shunji Yoshikawa, Taro Sasaoka, Yu Hatano, Ken Kurihara, Yasuhiro Maejima, Mitsuaki Isobe
BACKGROUND: Long-term dual antiplatelet therapy (DAPT) for patients treated with coronary stents has been reported to be effective. However the effectiveness of long-term DAPT for everolimus-eluting stent (EES) implanted patients has been controversial. We assessed the major adverse cardiac and cerebral events (MACCE: a composite of death, myocardial infarction, or cerebral arterial disease) in patients free from MACCE during the first 2 years after EES implantation. METHODS AND RESULTS: A total of 1918 patients who underwent successful percutaneous coronary intervention (PCI) with EES at 22 centers in Japan in 2010-2011 were enrolled, and 742 patients were free from MACCE for 2 years...
September 27, 2016: Journal of Cardiology
M Majidinia, E Alizadeh, B Yousefi, M Akbarzadeh, A Mihanfar, M Rahmati-Yamchi, N Zarghami
Background: Ovarian cancer is one of the most lethal gynecological malignancies and numerous changes in signaling cascades are involved in the initiation and progression of ovarian cancerous cells. Here, we investigated the role of NF-κB and Notch pathways inhibition on human ovarian cancer OVCAR-3 cells proliferation and IκB-α and Hes-1 expression as 2 key genes in these pathways regulation. Methods: The effects of Bay 11-7085 and DAPT, NF-κB and Notch pathways specific inhibitors, on cell proliferation were evaluated using MTT assay...
September 29, 2016: Drug Research
A Dias, E Franco, S Janzer, Nikoloz Koshkelashvili, V Bhalla, Manolo Rubio, Sarah Amanullah, Kathy Hebert, Vincent M Figueredo
Takotsubo cardiomyopathy (TTS) is a peculiar clinical condition often affecting postmenopausal women after a stressful trigger. The underlying mechanisms have not been completely elucidated but several hypotheses have been advanced, with catecholamine cardiotoxicity, microvascular dysfunction and coronary artery spasm each suggested to play a role. The incidence of stroke after TTS appears to range from 0% to 7.7%, and interestingly TTS has been described as both a cause and a complication of stroke. We sought to assess the incidence and predictors of stroke during the index event (peri-index event stroke) in a heterogeneous TTS population...
July 2016: Functional Neurology
Yi-Liang Bi, Min Min, Wei Shen, Yan Liu
The present study aims to evaluate whether repression of the Numb/Notch signaling pathway affects the radiosensitivity of human pancreatic cancer cell lines. Different doses of X-rays (0, 2, 3, 4, and 5 Gy) were applied to the PANC-1, SW1990, and MIA PaCa-2 human pancreatic cancer cell lines, and the Numb/Notch pathway inhibitor DAPT was added at different doses (0, 1, 3, and 5 μmol/l). MTT assay, colony formation assay, flow cytometry, scratch assay, and Transwell experiments were performed, and qRT-PCR and Western blot were conducted for the detection of Numb expression...
September 27, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
A Dias, E Franco, S Janzer, Nikoloz Koshkelashvili, V Bhalla, Manolo Rubio, Sarah Amanullah, Kathy Hebert, Vincent M Figueredo
Takotsubo cardiomyopathy (TTS) is a peculiar clinical condition often affecting postmenopausal women after a stressful trigger. The underlying mechanisms have not been completely elucidated but several hypotheses have been advanced, with catecholamine cardiotoxicity, microvascular dysfunction and coronary artery spasm each suggested to play a role. The incidence of stroke after TTS appears to range from 0% to 7.7%, and interestingly TTS has been described as both a cause and a complication of stroke. We sought to assess the incidence and predictors of stroke during the index event (peri-index event stroke) in a heterogeneous TTS population...
September 26, 2016: Functional Neurology
Ming-Lung Tsai, Chun-Chi Chen, Dong-Yi Chen, Chia-Hung Yang, Ming-Jer Hsieh, Cheng-Hung Lee, Chao-Yung Wang, Shang-Hung Chang, I-Chang Hsieh
Compared to bare metal stent (BMS) implantation, drug-eluting stents (DES) is significantly better in attenuating intimal hyperplasia and reducing the rate of revascularization. However, the requirement of prolonged dual antiplatelet therapy (DAPT) and the economic cost have been the major disadvantages of DES. Studies have shown that the use of DES in small vessels decrease revascularization rate, but the results in large vessels vary. Previous studies have shown that the extent of late loss is unrelated to vessel diameter, and that late loss is easily accommodated in large vessels, thus resulting in decreased clinical benefit of DES in this setting...
September 17, 2016: International Journal of Cardiology
Paola Pasquino, Roberto Canaparo, Tiziana Capello, Barbara Deorsola, Laura Perazzolo, Claudio Marengo, Loredana Serpe
We present a case report of a 52-year-old man who was hospitalized for right leg pain due to a relevant hemorrhagic effusion. He was on dual antiplatelet therapy (DAPT): acetylsalicylic acid and ticagrelor, a reversible P2Y12 receptor antagonist. Signs, symptoms, and laboratory blood tests led to the diagnosis of acquired hemophilia A (AHA). Ticagrelor therapy-associated AHA was hypothesized due to the fact that, before adding this drug, all laboratory and clinical examinations were repeatedly normal. Prednisone and cyclophosphamide treatment was started without DAPT interruption due to the high risk of stent thrombosis...
2016: Clinical Medicine Insights. Case Reports
Steven Sra, Mary K Tan, Shamir R Mehta, Harold N Fisher, Jean-Pierre Déry, Robert C Welsh, Mark J Eisenberg, Christopher B Overgaard, Barry F Rose, Anthony J Della Siega, Asim N Cheema, Brian Y L Wong, Mark A Henderson, Sohrab Lutchmedial, Shahar Lavi, Shaun G Goodman, Andrew T Yan
BACKGROUND: Since the introduction of newer, more potent P2Y12 receptor inhibitors (P2Y12ris), practice patterns and associated clinical outcomes in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and also requiring oral anticoagulation (OAC) have not been fully characterized. METHODS: The Canadian Observational Antiplatelet Study was a prospective, multicenter, longitudinal, observational study (26 hospitals, December 2011 to May 2013) describing P2Y12ri treatment patterns and outcomes in patients with ST-elevation and non-ST-elevation MI undergoing PCI...
October 2016: American Heart Journal
Jaya Chandrasekhar, Sameer Bansilal, Usman Baber, Samantha Sartori, Melissa Aquino, Serdar Farhan, Birgit Vogel, Michela Faggioni, Gennaro Giustino, Cono Ariti, Antonio Colombo, Alaide Chieffo, Annapoorna Kini, Richard Saporito, C Michael Gibson, Bernhard Witzenbichler, David Cohen, David Moliterno, Thomas Stuckey, Timothy Henry, Stuart Pocock, George Dangas, P Gabriel Steg, Roxana Mehran
BACKGROUND: Proton pump inhibitors (PPI) may decrease the availability of clopidogrel by competitive antagonism, leading to a potential increase in ischemic events. METHODS: We evaluated patients from the all-comer PARIS registry treated with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel following coronary stenting for outcomes stratified by PPI use. Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR), and net adverse cardiac events (NACE), composite of MACE or Bleeding Academic Research consortium (BARC) type 3 or 5 bleeding were assessed...
September 21, 2016: Catheterization and Cardiovascular Interventions
Masahiro Natsuaki, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Kenji Ando, Hiroki Shiomi, Toshiaki Toyota, Hirotoshi Watanabe, Koh Ono, Satoshi Shizuta, Takashi Tamura, Moriaki Inoko, Tsukasa Inada, Manabu Shirotani, Mitsuo Matsuda, Takeshi Aoyama, Tomoya Onodera, Satoru Suwa, Teruki Takeda, Katsumi Inoue, Takeshi Kimura
One-month duration of dual antiplatelet therapy (DAPT) has widely been adopted after bare-metal stent (BMS) implantation in the real clinical practice. However, it has not been adequately addressed yet whether DAPT for only 1-month could provide sufficient protection from ischemic events beyond 1-month after BMS implantation. We assessed the effects of short DAPT relative to prolonged DAPT on clinical outcomes with the landmark analysis at 2 month after BMS implantation. Among 13,058 consecutive patients enrolled in the CREDO-Kyoto registry cohort-2, this study population consisted of 4905 patients treated with BMS only in whom the information on the status of antiplatelet therapy was available at 2 month after stent implantation [single-antiplatelet therapy (SAPT) group: N = 2575 (acute myocardial infarction (AMI): N = 1257, and non-AMI: N = 1318), and DAPT group: N = 2330 (AMI: N = 1304, and non-AMI: N = 1026)]...
September 19, 2016: Cardiovascular Intervention and Therapeutics
Mi Hee Cho, Dong Wook Shin, Jae Moon Yun, Joong Hyun Shin, Seung Pyo Lee, Hyejin Lee, Yoo Kyoung Lim, Eun Ha Kim, Hyun Kyoung Kim
The administration of antiplatelet drugs for months after a drug-eluting stent implantation is critical in decreasing the risk of complications, and premature discontinuation of antiplatelet therapy before the recommended period is the most important predictor for late complications. Therefore, we investigated the prevalence and associated factors of premature discontinuation of antiplatelet therapy in patients in Korea. This retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort data...
August 22, 2016: American Journal of Cardiology
David Reichman, Limor Man, Laura Park, Raphael Lis, Jeannine Gerhardt, Zev Rosenwaks, Daylon James
During development, endothelial cells (EC) display tissue-specific attributes that are unique to each vascular bed, as well as generic signaling mechanisms that are broadly applied to create a patent circulatory system. We have previously utilized human embryonic stem cells (hESC) to generate tissue-specific EC sub-types (Rafii et al., 2013) and identify pathways that govern growth and trans-differentiation potential of hESC-derived ECs (James et al., 2010). Here, we elucidate a novel Notch-dependent mechanism that induces endothelial to mesenchymal transition (EndMT) in confluent monolayer cultures of hESC-derived ECs...
September 13, 2016: Stem Cell Research
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