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Publisher: Springer-Verlag (Total: 2350 journals)

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Showing 1 - 200 of 2350 Journals sorted alphabetically
3D Printing in Medicine     Open Access   (Followers: 1)
3D Research     Hybrid Journal   (Followers: 21, SJR: 0.222, CiteScore: 1)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.825, CiteScore: 1)
AAPS J.     Hybrid Journal   (Followers: 22, SJR: 1.118, CiteScore: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 7, SJR: 0.752, CiteScore: 3)
Abdominal Imaging     Hybrid Journal   (Followers: 15, SJR: 0.866, CiteScore: 2)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 4, SJR: 0.439, CiteScore: 0)
Academic Psychiatry     Full-text available via subscription   (Followers: 25, SJR: 0.53, CiteScore: 1)
Academic Questions     Hybrid Journal   (Followers: 8, SJR: 0.106, CiteScore: 0)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 27, SJR: 0.316, CiteScore: 1)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.359, CiteScore: 1)
Acoustics Australia     Hybrid Journal   (SJR: 0.232, CiteScore: 1)
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.367, CiteScore: 0)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.675, CiteScore: 1)
Acta Biotheoretica     Hybrid Journal   (Followers: 4, SJR: 0.284, CiteScore: 1)
Acta Diabetologica     Hybrid Journal   (Followers: 18, SJR: 1.587, CiteScore: 3)
Acta Endoscopica     Hybrid Journal   (Followers: 1)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.769, CiteScore: 1)
Acta Geochimica     Hybrid Journal   (Followers: 7, SJR: 0.24, CiteScore: 1)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 2, SJR: 0.305, CiteScore: 1)
Acta Geophysica     Hybrid Journal   (Followers: 10, SJR: 0.312, CiteScore: 1)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.588, CiteScore: 3)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.517, CiteScore: 1)
Acta Mathematica     Hybrid Journal   (Followers: 12, SJR: 7.066, CiteScore: 3)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.452, CiteScore: 1)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 6, SJR: 0.379, CiteScore: 1)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.27, CiteScore: 0)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.208, CiteScore: 0)
Acta Mechanica     Hybrid Journal   (Followers: 21, SJR: 1.04, CiteScore: 2)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.607, CiteScore: 2)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7, SJR: 0.576, CiteScore: 2)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.638, CiteScore: 1)
Acta Neurochirurgica     Hybrid Journal   (Followers: 6, SJR: 0.822, CiteScore: 2)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 1, SJR: 0.376, CiteScore: 1)
Acta Neuropathologica     Hybrid Journal   (Followers: 5, SJR: 7.589, CiteScore: 12)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.334, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 15, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8, SJR: 0.103, CiteScore: 0)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 23, SJR: 0.72, CiteScore: 2)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 16, SJR: 1.005, CiteScore: 2)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.703, CiteScore: 2)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 4, SJR: 0.698, CiteScore: 1)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 37, SJR: 0.956, CiteScore: 2)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 19, SJR: 0.812, CiteScore: 1)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 55, SJR: 1.09, CiteScore: 1)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.144, CiteScore: 0)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 28, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 44, SJR: 1.04, CiteScore: 3)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 1.075, CiteScore: 3)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 6)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.517, CiteScore: 1)
Aerobiologia     Hybrid Journal   (Followers: 3, SJR: 0.673, CiteScore: 2)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 9, SJR: 0.825, CiteScore: 1)
African Archaeological Review     Hybrid Journal   (Followers: 16, SJR: 0.862, CiteScore: 1)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.235, CiteScore: 0)
AGE     Hybrid Journal   (Followers: 7)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.39, CiteScore: 1)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.67, CiteScore: 2)
Agricultural Research     Hybrid Journal   (Followers: 6, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Hybrid Journal   (Followers: 20, SJR: 0.663, CiteScore: 1)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 12, SJR: 1.864, CiteScore: 6)
AI & Society     Hybrid Journal   (Followers: 8, SJR: 0.227, CiteScore: 1)
AIDS and Behavior     Hybrid Journal   (Followers: 14, SJR: 1.792, CiteScore: 3)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 4, SJR: 0.862, CiteScore: 3)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 6, SJR: 0.531, CiteScore: 0)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.583, CiteScore: 1)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 1.095, CiteScore: 1)
Algorithmica     Hybrid Journal   (Followers: 9, SJR: 0.56, CiteScore: 1)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.234, CiteScore: 0)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 5, SJR: 1.11, CiteScore: 3)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
AMBIO     Hybrid Journal   (Followers: 10, SJR: 1.569, CiteScore: 4)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 16, SJR: 0.951, CiteScore: 3)
American J. of Community Psychology     Hybrid Journal   (Followers: 29, SJR: 1.329, CiteScore: 2)
American J. of Criminal Justice     Hybrid Journal   (Followers: 8, SJR: 0.772, CiteScore: 1)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 16, SJR: 0.46, CiteScore: 1)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.181, CiteScore: 0)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.611, CiteScore: 1)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 21, SJR: 0.314, CiteScore: 0)
American Sociologist     Hybrid Journal   (Followers: 12, SJR: 0.35, CiteScore: 0)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.135, CiteScore: 3)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 7, SJR: 0.211, CiteScore: 1)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 5, SJR: 0.536, CiteScore: 1)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 5)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 32, SJR: 0.978, CiteScore: 3)
Anatomical Science Intl.     Hybrid Journal   (Followers: 2, SJR: 0.367, CiteScore: 1)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.177, CiteScore: 5)
Animal Cognition     Hybrid Journal   (Followers: 19, SJR: 1.389, CiteScore: 3)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.192, CiteScore: 0)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.097, CiteScore: 2)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4, SJR: 0.438, CiteScore: 0)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.429, CiteScore: 0)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.197, CiteScore: 1)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18, SJR: 1.042, CiteScore: 3)
Annals of Combinatorics     Hybrid Journal   (Followers: 4, SJR: 0.932, CiteScore: 1)
Annals of Data Science     Hybrid Journal   (Followers: 12)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.85, CiteScore: 2)
Annals of Finance     Hybrid Journal   (Followers: 30, SJR: 0.579, CiteScore: 1)
Annals of Forest Science     Hybrid Journal   (Followers: 7, SJR: 0.986, CiteScore: 2)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.228, CiteScore: 1)
Annals of Hematology     Hybrid Journal   (Followers: 15, SJR: 1.043, CiteScore: 2)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.413, CiteScore: 1)
Annals of Microbiology     Hybrid Journal   (Followers: 11, SJR: 0.479, CiteScore: 2)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 4, SJR: 0.687, CiteScore: 2)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.943, CiteScore: 2)
Annals of Ophthalmology     Hybrid Journal   (Followers: 11)
Annals of Regional Science     Hybrid Journal   (Followers: 7, SJR: 0.614, CiteScore: 1)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 9, SJR: 0.239, CiteScore: 1)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 13, SJR: 1.986, CiteScore: 4)
Annals of Telecommunications     Hybrid Journal   (Followers: 9, SJR: 0.223, CiteScore: 1)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 1.495, CiteScore: 1)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.834, CiteScore: 2)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.22, CiteScore: 3)
APOPTOSIS     Hybrid Journal   (Followers: 8, SJR: 1.424, CiteScore: 4)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.294, CiteScore: 1)
Applications of Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.602, CiteScore: 1)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 43, SJR: 0.571, CiteScore: 2)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17, SJR: 0.21, CiteScore: 1)
Applied Cancer Research     Open Access  
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.49, CiteScore: 0)
Applied Composite Materials     Hybrid Journal   (Followers: 49, SJR: 0.58, CiteScore: 2)
Applied Entomology and Zoology     Partially Free   (Followers: 4, SJR: 0.422, CiteScore: 1)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.733, CiteScore: 3)
Applied Geophysics     Hybrid Journal   (Followers: 8, SJR: 0.488, CiteScore: 1)
Applied Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.6, CiteScore: 2)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.319, CiteScore: 1)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 8, SJR: 0.886, CiteScore: 1)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.17, CiteScore: 0)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.461, CiteScore: 1)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 64, SJR: 1.182, CiteScore: 4)
Applied Physics A     Hybrid Journal   (Followers: 9, SJR: 0.481, CiteScore: 2)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 24, SJR: 0.74, CiteScore: 2)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.519, CiteScore: 2)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 12, SJR: 0.316, CiteScore: 1)
Applied Solar Energy     Hybrid Journal   (Followers: 18, SJR: 0.225, CiteScore: 0)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 5, SJR: 0.542, CiteScore: 1)
Aquaculture Intl.     Hybrid Journal   (Followers: 24, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 2)
Aquatic Ecology     Hybrid Journal   (Followers: 34, SJR: 0.656, CiteScore: 2)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.591, CiteScore: 1)
Aquatic Sciences     Hybrid Journal   (Followers: 13, SJR: 1.109, CiteScore: 3)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.303, CiteScore: 1)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 2, SJR: 0.319, CiteScore: 1)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 20, SJR: 1.052, CiteScore: 2)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.224, CiteScore: 0)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.725, CiteScore: 1)
Archival Science     Hybrid Journal   (Followers: 60, SJR: 0.745, CiteScore: 2)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 7, SJR: 0.186, CiteScore: 1)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 3, SJR: 0.909, CiteScore: 1)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 3.93, CiteScore: 3)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Archives and Museum Informatics     Hybrid Journal   (Followers: 143, SJR: 0.101, CiteScore: 0)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 5, SJR: 1.41, CiteScore: 5)
Archives of Dermatological Research     Hybrid Journal   (Followers: 7, SJR: 1.006, CiteScore: 2)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 14, SJR: 0.773, CiteScore: 2)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 16, SJR: 0.956, CiteScore: 2)
Archives of Microbiology     Hybrid Journal   (Followers: 8, SJR: 0.644, CiteScore: 2)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 8, SJR: 1.146, CiteScore: 2)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 0.71, CiteScore: 2)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 10, SJR: 1.493, CiteScore: 3)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.541, CiteScore: 5)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 0.973, CiteScore: 2)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 14, SJR: 1.274, CiteScore: 3)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 0.946, CiteScore: 3)
ArgoSpine News & J.     Hybrid Journal  
Argumentation     Hybrid Journal   (Followers: 6, SJR: 0.349, CiteScore: 1)
Arid Ecosystems     Hybrid Journal   (Followers: 2, SJR: 0.2, CiteScore: 0)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.766, CiteScore: 1)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1, SJR: 0.355, CiteScore: 0)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 2, SJR: 0.839, CiteScore: 2)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.131, CiteScore: 0)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 11, SJR: 0.937, CiteScore: 2)
Artificial Intelligence Review     Hybrid Journal   (Followers: 15, SJR: 0.833, CiteScore: 4)
Artificial Life and Robotics     Hybrid Journal   (Followers: 9, SJR: 0.226, CiteScore: 0)
Asia Europe J.     Hybrid Journal   (Followers: 5, SJR: 0.504, CiteScore: 1)
Asia Pacific Education Review     Hybrid Journal   (Followers: 12, SJR: 0.479, CiteScore: 1)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 16, SJR: 1.185, CiteScore: 2)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 12, SJR: 0.353, CiteScore: 1)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.187, CiteScore: 0)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 19, SJR: 0.855, CiteScore: 1)
Asian Business & Management     Hybrid Journal   (Followers: 9, SJR: 0.378, CiteScore: 1)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 9)
Asian J. of Criminology     Hybrid Journal   (Followers: 6, SJR: 0.543, CiteScore: 1)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 3, SJR: 0.548, CiteScore: 1)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.183, CiteScore: 0)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  

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Journal Cover
American Journal of Cardiovascular Drugs
Journal Prestige (SJR): 0.951
Citation Impact (citeScore): 3
Number of Followers: 16  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1175-3277 - ISSN (Online) 1179-187X
Published by Springer-Verlag Homepage  [2350 journals]
  • Stable but Progressive Nature of Heart Failure: Considerations for Primary
           Care Physicians
    • Authors: Inder Anand
      Pages: 333 - 345
      Abstract: Primary care physicians play a significant role in managing heart failure (HF), with the goals of reducing mortality, avoiding hospitalization, and improving patients’ quality of life. Most HF-related hospitalizations and deaths occur in patients with New York Heart Association functional class II or III, many of whom are perceived to have stable disease, which often progresses without clinical symptoms due to underlying deleterious effects of neurohormonal imbalance and endothelial dysfunction. Management includes lifestyle changes and stepped pharmacological therapy directed at the four stages of HF, with aggressive uptitration of therapies, including beta-blockers and inhibitors of the renin-angiotensin-aldosterone system. Recently, two new HF treatments have become available in clinical practice. Ivabradine was approved to reduce the risk of hospitalization for HF in patients with stable, symptomatic HF. Additionally, the angiotensin receptor–neprilysin inhibitor (ARNI), sacubitril/valsartan, was found to be significantly superior to enalapril in reducing risks of cardiovascular death and HF-related hospitalization. The respective 2016 and 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America clinical practice guideline updates recommend that patients taking angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy be switched to ARNI therapy to further reduce morbidity and mortality. For HF management to be maximally effective, physicians must be knowledgeable about the risks and benefits of treatments and stay engaged with patients to identify signs of disease progression. This article provides an overview of the progressive nature of HF in apparently stable patients and describes areas for treatment improvement that may help to optimize patient care.
      PubDate: 2018-10-01
      DOI: 10.1007/s40256-018-0277-0
      Issue No: Vol. 18, No. 5 (2018)
  • Atrial Fibrillation in Patients with Heart Failure: Current State and
           Future Directions
    • Authors: Tuoyo O. Mene-Afejuku; Persio D. López; Adedoyin Akinlonu; Carissa Dumancas; Ferdinand Visco; Savi Mushiyev; Gerald Pekler
      Pages: 347 - 360
      Abstract: Heart failure affects nearly 26 million people worldwide. Patients with heart failure are frequently affected with atrial fibrillation, and the interrelation between these pathologies is complex. Atrial fibrillation shares the same risk factors as heart failure. Moreover, it is associated with a higher-risk baseline clinical status and higher mortality rates in patients with heart failure. The mechanisms by which atrial fibrillation occurs in a failing heart are incompletely understood, but animal studies suggest they differ from those that occur in a healthy heart. Data suggest that heart failure-induced atrial fibrosis and atrial ionic remodeling are the underlying abnormalities that facilitate atrial fibrillation. Therapeutic considerations for atrial fibrillation in patients with heart failure include risk factor modification and guideline-directed medical therapy, anticoagulation, rate control, and rhythm control. As recommended for atrial fibrillation in the non-failing heart, anticoagulation in patients with heart failure should be guided by a careful estimation of the risk of embolic events versus the risk of hemorrhagic episodes. The decision whether to target a rate-control or rhythm-control strategy is an evolving aspect of management. Currently, both approaches are good medical practice, but recent data suggest that rhythm control, particularly when achieved through catheter ablation, is associated with improved outcomes. A promising field of research is the application of neurohormonal modulation to prevent the creation of the “structural substrate” for atrial fibrillation in the failing heart.
      PubDate: 2018-10-01
      DOI: 10.1007/s40256-018-0276-1
      Issue No: Vol. 18, No. 5 (2018)
  • Vitamins for Prevention of Contrast-induced Acute Kidney Injury: A
           Systematic Review and Trial Sequential Analysis
    • Authors: Yongxing Xu; Xinming Zheng; Boran Liang; Jianjun Gao; Zhaoyan Gu
      Pages: 373 - 386
      Abstract: Background To date, universally accepted preventive measures for contrast-induced acute kidney injury (CI-AKI) do not exist, and they warrant further research. Objective The purpose of this study was to evaluate the efficacy of vitamins, including vitamin C and E, for prevention of CI-AKI. Methods We electronically searched the MEDLINE, EMBASE, and Cochrane databases. The outcome of interest was the incidence of CI-AKI. Results A total of 19 studies were included in this meta-analysis. Pooled analysis showed that vitamin C plus saline [relative risk (RR) = 0.63, 95% confidence interval (CI) 0.49–0.82, p = 0.0005] and vitamin E plus saline (RR = 0.39, 95% CI 0.24–0.62, p < 0.0001) significantly reduced the incidence of CI-AKI compared to saline alone. The effect of vitamin C plus saline was further confirmed by trial sequential analysis (TSA). However, TSA indicated that more trials are required to confirm the efficacy of vitamin E plus saline. There was no significant difference in preventing CI-AKI between vitamin C and N-acetylcysteine (NAC) (RR = 0.90, 95% CI 0.47–1.71, p = 0.75), between vitamin C plus NAC and saline (RR = 0.62, 95% CI 0.30–1.30, p =  0.20), as well as between vitamin C plus NAC and NAC (RR = 0.97, 95% CI 0.49–1.92, p = 0.93). Conclusions Vitamin C plus saline administration is effective at reducing the risk of CI-AKI. Evidence for the use of vitamin E plus saline in this context is encouraging, but more trials are required. Furthermore, this meta-analysis and TSA indicated insufficient power to draw a definitive conclusion on the effect of vitamin C plus NAC, versus saline or NAC alone, which needs to be explored further.
      PubDate: 2018-10-01
      DOI: 10.1007/s40256-018-0274-3
      Issue No: Vol. 18, No. 5 (2018)
  • Efficacy and Safety of Intravenous Tenecteplase Bolus in Acute Ischemic
           Stroke: Results of Two Open-Label, Multicenter Trials
    • Authors: Tirppur C. R. Ramakrishnan; For the Tenecteplase in Stroke Investigators; Somasundaram Kumaravelu; Sunil K. Narayan; Sai S. Buddha; Ch. Murali; Palakkapparampil H. A. Majeed; Salvadeeswaran Meenakshi-Sundaram; Rustom S. Wadia; Vikram Sharma; Indraneel Basu; Pamidimukkala Vijaya; Kizhakkaniyakath A. Salam; Shahid Barmare; Zubin Vaid; K. K. Nirmal Raj; Pandurang R. Wattamwar; Konbappan Asokan; Vijaykumar Dhonge; Shankara Nellikunja; Deepak Namjoshi; Rangasetty Srinivasa; Deepak S. Laddhad; Shirish D. Deshpande; Balakrishnan Raghunath; Jayantee Kalita; Mritunjai Kumar; Usha K. Misra; Methil Pradeep
      Pages: 387 - 395
      Abstract: Background Tenecteplase (TNK-tPA) is a promising third-generation plasminogen activator, because of its greater fibrin specificity and longer half-life than alteplase. There is a paucity of studies on intravenous thrombolysis using TNK-tPA in developing countries. The present study has been undertaken to compare the efficacy and safety of TNK-tPA with alteplase. Methods Two studies were conducted. Study I was an open-label, randomized study in which two doses of TNK-tPA (0.1 and 0.2 mg/kg) were compared. Study II was an open-label study in which TNK-tPA 0.2 mg/kg bolus was compared with historical controls. The primary endpoint for study I and study II was an improvement of ≥ 8 points or a score of 0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological improvement (MNI)] at 24 h. Secondary endpoints for both studies were neurological improvement as assessed using the NIHSS score, modified Rankin Scale (mRS) score and the Barthel Index (BI) on days 7, 30 and 90. Minimal disability was defined as an mRS score of 0 or 1 and good functional recovery as a BI score of 50–90. Safety was assessed by the proportion of patients having symptomatic intracranial hemorrhage (sICH) within 36 h and asymptomatic intracranial hemorrhage at 48 h after treatment. Results In study I, 20 patients received 0.1 mg/kg and 30 received 0.2 mg/kg TNK-tPA. There was no significant difference in MNI at 24 h between 0.1 and 0.2 mg/kg TNK-tPA doses. The patients given 0.2 mg/kg TNK-tPA had a significantly better 3-month outcome (minimal disability, p = 0.007). There was no sICH in study I. In study II, 62 patients (one lost to follow-up) received 0.2 mg/kg TNK-tPA. MNI was noted in ten patients (16.4%), 3-month minimal disability was noted in 37 patients (60.7%), and good functional recovery was seen in 33 patients (54.1%). sICH occurred in one patient, and four patients died. Pooled data of patients in study I and study II receiving 0.2 mg/kg TNK-tPA were compared with data from the historical National Institute of Neurological Disorders and Stroke (NINDS) trial. For comparison, the primary endpoint of the NINDS trial (improvement on NIHSS of ≥ 4 points or a score of 0 at 24 h) was taken. The primary endpoint though was not significantly different (58.2% vs. 47%, p = 0.08), but with TNK-tPA, greater neurological improvement, minimal disability (70.3 vs. 39%, p < 0.001) and good functional recovery (36.3 vs. 16%, p < 0.001) was noted at 3 months. There was a lower incidence of sICH (1.1 vs. 6.4%, p = 0.05) and lower 3-month mortality (5.5 vs. 17%, p = 0.01) noted with TNK-tPA compared with alteplase. Conclusions Intravenous TNK-tPA 0.2 mg/kg administered within 3 hours of symptom onset seems to be well tolerated and effective option in patients with acute ischemic stroke. Trial Registration Clinical Trials Registry—India,; unique identifiers: CTRI/2009/091/000251 and CTRI/2015/02/005556.
      PubDate: 2018-10-01
      DOI: 10.1007/s40256-018-0284-1
      Issue No: Vol. 18, No. 5 (2018)
  • Treatment with Mannitol is Associated with Increased Risk for In-Hospital
           Mortality in Patients with Acute Ischemic Stroke and Cerebral Edema
    • Authors: Marianthi Papagianni; Konstantinos Tziomalos; Stavroula Kostaki; Stella-Maria Angelopoulou; Konstantinos Christou; Stella D. Bouziana; Maria Vergou; Triantafyllos Didangelos; Christos Savopoulos; Apostolos I. Hatzitolios
      Pages: 397 - 403
      Abstract: Background Current guidelines state that osmotic therapy is reasonable in patients with clinical deterioration from cerebral infarction-related cerebral edema. However, there are limited data on the safety and efficacy of this therapy. We aimed to evaluate the effect of mannitol on the outcome of ischemic stroke-related cerebral edema. Methods and Results We prospectively studied 922 consecutive patients admitted with acute ischemic stroke. Patients who showed space-occupying brain edema with tissue shifts compressing the midline structures received mannitol. The outcome was assessed with dependency rates at discharge (modified Rankin Scale grade 2–5) and in-hospital mortality. Rates of dependency were higher in patients treated with mannitol (n = 86) than in those who were not (97.7 and 58.5%, respectively; p < 0.001). Independent predictors of dependency were age, history of ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) score at admission. Rates of mortality were higher in patients treated with mannitol than in those who were not (46.5 and 5.6%, respectively; p < 0.001). Independent predictors of in-hospital mortality were diastolic blood pressure [relative risk (RR) 1.05, 95% confidence interval (CI) 1.02–1.08, p < 0.001], NIHSS score at admission (RR 1.19, 95% CI 1.14–1.23, p < 0.001) and treatment with mannitol (RR 3.45, 95% CI 1.55–7.69, p < 0.005). Conclusions Administration of mannitol to patients with ischemic stroke-related cerebral edema does not appear to affect the functional outcome and might increase mortality, independently of stroke severity.
      PubDate: 2018-10-01
      DOI: 10.1007/s40256-018-0285-0
      Issue No: Vol. 18, No. 5 (2018)
  • Comparative Effectiveness of Inclisiran 100, 300, and 500 mg in a
           Population with Hyperlipidemia: A Network Meta-Analysis of Randomized
           Controlled Trials
    • Authors: Yang Wang; Jinsong Wang; Shenming Wang
      Pages: 271 - 282
      Abstract: Background To our knowledge, inclisiran was the first agent composed of small interfering RNAs (siRNAs) to be preliminarily used to reduce proatherogenic lipoprotein cholesterol levels. Inclisiran was evaluated in large clinical trials but did not receive government approval. The ability of inclisiran to reduce low-density lipoprotein cholesterol (LDL-C) greatly improved its chances of becoming a novel therapeutic option for patients with hyperlipidemia. Objective Our goal was to summarize the preliminary effectiveness and safety data for inclisiran. Methods We conducted a comprehensive search of PubMed, Scopus, Web of Science, the OVID EMB Reviews database, and Clinical Trials with the keyword “inclisiran” to find all related randomized controlled trials (RCTs). Five recently published RCTs involving 583 adults aged 18–65 years with hyperlipidemia were included in the analysis. Results Subgroup analysis suggested that inclisiran 100 mg (standard mean difference [SMD] − 2.09; 95% confidence interval [CI] − 2.51 to − 1.66; p < 0.05), 300 mg (SMD − 2.74; 95% CI − 3.61 to − 1.87; p < 0.05), and 500 mg (SMD − 2.21; 95% CI − 2.62 to − 1.80; p < 0.05) significantly (p < 0.05) reduced LDL-C and total cholesterol even though pooled analysis showed no LDL-C-lowering effect (SMD 0.15; 95% CI − 0.34 to 0.04; p = 0.116). Compared with patients receiving placebo, pooled and subgroup analysis of patients receiving inclisiran showed no favorable changes in triglycerides or high-density lipoprotein cholesterol (p > 0.05). The most commonly reported adverse events were musculoskeletal pain, nasopharyngitis, headache, and elevated C-reactive protein (CRP), none of which were significant (p > 0.05). Conclusions To date, inclisiran has been effective in treating hyperlipidemia. Major adverse events were not identified, although other possible adverse events may be discovered with more RCTs and extensive long-term follow-up.
      PubDate: 2018-08-01
      DOI: 10.1007/s40256-018-0270-7
      Issue No: Vol. 18, No. 4 (2018)
  • Effect of Oral Branched-Chain Amino Acids on Serum Albumin Concentration
           in Heart Failure Patients with Hypoalbuminemia: Results of a Preliminary
    • Authors: Yuichi Uchino; Masafumi Watanabe; Munenori Takata; Eisuke Amiya; Kensuke Tsushima; Takeshi Adachi; Yukio Hiroi; Toshikazu Funazaki; Issei Komuro
      Pages: 327 - 332
      Abstract: Background We conducted a randomized, controlled trial to determine whether supplementation with oral branched-chain amino acids (BCAAs) improves serum albumin and clinical outcomes in heart failure (HF) patients with hypoalbuminemia. Methods and results We randomly assigned 18 in-hospital HF patients with serum albumin < 3.5 g/dL to receive oral BCAA granules (LIVACT®) for 28 days during their hospital stay or until discharge (BCAA group; N = 9) or to receive no supplementation (controls; N = 9), in addition to recommended HF therapy. The primary endpoints were changes from baseline in serum albumin and cardiothoracic ratio (CTR). Sixteen patients completed the study. The mean (± standard deviation) period of BCAA supplementation was 18.4 ± 8.4 days. Serum albumin significantly increased in the BCAA group [mean difference vs baseline, 0.44 g/dL; 95% confidence interval (CI) 0.13–0.76; P = 0.014] and did not change in controls (0.18 g/dL; 95% CI − 0.05 to 0.40; P = 0.108). CTR significantly decreased in the BCAA group (− 2.3%; 95% CI − 3.8 to − 0.8; P = 0.014) and did not change in controls (− 1.0%; 95% CI − 2.3 to 0.3; P = 0.111). Conclusion In-hospital HF patients with hypoalbuminemia supplemented with BCAAs showed increased serum albumin and decreased CTR. Clinical trial registration number UMIN000004488 []
      PubDate: 2018-08-01
      DOI: 10.1007/s40256-018-0269-0
      Issue No: Vol. 18, No. 4 (2018)
  • A Meta-Analysis of the Effect of PCSK9-Monoclonal Antibodies on
           Circulating Lipoprotein (a) Levels
    • Authors: Ye-Xuan Cao; Hui-Hui Liu; Sha Li; Jian-Jun Li
      Abstract: Background Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein. While no effective therapy for Lp(a) is currently available, recently, several pooled analyses with small sample sizes have suggested that proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs) could reduce circulating Lp(a) levels. This meta-analysis was performed to comprehensively investigate the efficacy of PCSK9-mAbs with respect to serum Lp(a) concentrations. Methods PubMed, MEDLINE, Embase,, Cochrane CENTRAL, Web of Science and recent conferences up to July 2018 were searched. Randomized clinical trials evaluating the effect of PCSK9-mAbs and control treatment on plasma Lp(a) concentrations were included. Mean differences and odds ratios with 95% confidence intervals (CIs) were used. Results Twenty-seven randomized clinical trials with a total of 11,864 participants were included. PCSK9-mAbs showed a significant efficacy in reducing Lp(a) (− 21.9%, 95% CI − 24.3 to − 19.5), irrespective of PCSK9-mAb types, treatment duration, participant characteristics, treatment methods, differences of control treatment, baseline Lp(a) levels, and test methods. The greatest reduction was achieved with 150 mg alirocumab biweekly (− 24.6%, 95% CI − 28.0 to − 21.2) and  140 mg evolocumab monthly (− 26.8%, 95% CI − 31.6 to − 21.9). Meta-regression analyses found that the more intense low-density lipoprotein cholesterol levels declined during PCSK9-mAb treatment, the greater the reduction in Lp(a) levels. Safety was in accordance with previous reports. Conclusions The results of this analysis suggested that PCSK9-mAbs could significantly reduce circulating Lp(a) levels. Long-term studies may be needed to confirm the effect of PCSK9-mAbs on Lp(a) in the future.
      PubDate: 2018-09-19
      DOI: 10.1007/s40256-018-0303-2
  • Idarucizumab for Reversal of Dabigatran: Single-Center Real-World
    • Authors: Marwan Sheikh-Taha
      Abstract: Background Idarucizumab is used to reverse the effects of dabigatran. Information on the use of idarucizumab in the clinical setting remains very limited. Objective The objective of this study was to describe clinical experience with idarucizumab in a large medical teaching center in the USA. Methods Patients who received idarucizumab to reverse the effects of dabigatran between 1 January 2016 and 30 June 2018 were studied. In patients with major bleeding, the efficacy of idarucizumab was assessed using criteria of the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee. The course of treatment and clinical outcomes in patients who received idarucizumab for emergency surgery or procedures are described. Results In total, 13 patients received idarucizumab for atrial fibrillation during the study period. Their mean age was 77.5 ± 7.1 years, and 12 (92.3%) were men. Idarucizumab was used in 11 patients for major bleeding events and in two patients for emergency surgery or procedures. Intracranial hemorrhage (n = 6) and gastrointestinal bleed (n = 2) were the most common types of bleeding. Clinical hemostasis was achieved in 8 of 11 (72.7%) patients with major bleeding. One patient with acute kidney injury needed two doses of the reversal agent to achieve hemostasis. One patient underwent open heart surgery and developed postoperative hemorrhage despite receiving idarucizumab. None of the patients experienced thrombotic complications or side effects that could be attributed to idarucizumab. Conclusion Real-world experience in a US hospital with the use of idarucizumab in emergency situations requiring the reversal of the effects of dabigatran is described. Idarucizumab represents an exciting new antidote for dabigatran, but clinical efficacy and cost-effectiveness data remain lacking.
      PubDate: 2018-09-11
      DOI: 10.1007/s40256-018-0300-5
  • Efficacy and Safety of the Use of Non-vitamin K Antagonist Oral
           Anticoagulants in Patients with Ischemic Heart Disease: A Meta-Analysis of
           Phase III Randomized Trials
    • Authors: Linghua Fu; Wengen Zhu; Lin Huang; Jinzhu Hu; Jianyong Ma; Gregory Y. H. Lip; Kui Hong
      Abstract: Background There are conflicting published data on non-vitamin K antagonist oral anticoagulants (NOACs), with varying evidence of benefit or harm in acute coronary syndrome (ACS) and non-ACS cohorts. To explore the efficacy and safety of NOAC use in patients with ischemic heart disease (IHD), we conducted a meta-analysis of phase III randomized controlled trials (RCTs). Methods We systematically searched the Cochrane Library, PubMed, and Embase databases. A random-effect model was selected to pool the effect measurement estimates (hazard ratios [HRs] and 95% confidence intervals [CIs]). Results Three RCTs with 39,492 enrolled IHD patients were included. Compared with placebo, NOACs were associated with reduced risks of major adverse cardiac events (MACE) (HR 0.83, 95% CI 0.76–0.90), cardiovascular death (HR 0.82, 95% CI 0.72–0.93), and myocardial infarction (HR 0.87, 95% CI 0.78–0.97) accompanied by increased risks of major bleeding (HR 2.46, 95% CI 1.42–4.26), but not fatal bleeding (HR 1.35, 95% CI 0.76–2.39) or intracranial hemorrhage (HR 2.19, 95% CI 0.91–5.27). Subgroup analysis revealed that NOACs were associated with an increased risk of major bleeding in patients who received dual antiplatelet therapy compared with patients who received single antiplatelet therapy (3.01, 1.82–4.98 vs. 1.66, 1.37–2.03; P for interaction 0.03) and patients with ACS compared with patients with non-ACS (3.27, 2.16–4.95 vs. 1.66, 1.36–2.02; P for interaction 0.004). Conclusions In patients with IHD, NOACs confer protection against thrombosis-related complications, but at the cost of an increased hazard of major bleeding. NOACs plus a single antiplatelet drug seem to be a good choice for patients with IHD.
      PubDate: 2018-09-04
      DOI: 10.1007/s40256-018-0299-7
  • The Effect of Bromodomain and Extra-Terminal Inhibitor Apabetalone on
           Attenuated Coronary Atherosclerotic Plaque: Insights from the ASSURE Trial
    • Authors: Daisuke Shishikura; Yu Kataoka; Satoshi Honda; Kohei Takata; Susan W. Kim; Jordan Andrews; Peter J. Psaltis; Michael Sweeney; Ewelina Kulikowski; Jan Johansson; Norman C. W. Wong; Stephen J. Nicholls
      Abstract: Background Apabetalone is a selective bromodomain and extra-terminal (BET) inhibitor which modulates lipid and inflammatory pathways implicated in atherosclerosis. The impact of apabetalone on attenuated coronary atherosclerotic plaque (AP), a measure of vulnerability, is unknown. Methods The ApoA-1 Synthesis Stimulation and intravascular Ultrasound for coronary atheroma Regression Evaluation (ASSURE; NCT01067820) study employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in 281 patients treated with apabetalone or placebo for 26 weeks. AP was measured at baseline and follow-up. Factors associated with changes in AP were investigated. Results AP was observed in 31 patients (11%) [27 (13.0%) in the apabetalone group and four (5.5%) in the placebo group]. The apabetalone group demonstrated reductions in AP length by − 1 mm [interquartile range (IQR) − 4, 1] (p = 0.03), AP arc by − 37.0° (IQR − 59.2, 8.2) (p = 0.003) and the AP index by − 34.6 mm° (IQR − 52.6, 10.1) (p = 0.003) from baseline. The change in AP index correlated with on-treatment concentration of high-density lipoprotein (HDL) particles (r = − 0.52, p = 0.006), but not HDL cholesterol (r = − 0.11, p = 0.60) or apolipoprotein A-1 (r = − 0.16, p = 0.43). Multivariable analysis revealed that on-treatment concentrations of HDL particles (p = 0.03) and very low-density lipoprotein particles (p = 0.01) were independently associated with changes in AP index. Conclusions Apabetalone favorably modulated ultrasonic measures of plaque vulnerability in the population studied, which may relate to an increase in HDL particle concentrations. The clinical implications are currently being investigated in the phase 3 major adverse cardiac event outcomes trial BETonMACE.
      PubDate: 2018-08-28
      DOI: 10.1007/s40256-018-0298-8
  • Healthcare Utilization and Expenditures in Working-Age Adults with Atrial
           Fibrillation: The Effect of Switching from Warfarin to Non-Vitamin K Oral
    • Authors: Xue Feng; Usha Sambamoorthi; Kim Innes; Traci LeMasters; Gregory Castelli; Nilanjana Dwibedi; Xi Tan
      Abstract: Objective Our objective was to evaluate the association between switching from warfarin to non-vitamin K oral anticoagulants (NOACs) and potential drug–drug interactions (DDIs), healthcare utilization, and expenditures in working-age adults with atrial fibrillation (AF). Methods We conducted a retrospective cohort study using data from 2010 to 2015 for patients who switched from warfarin to NOACs (switchers) and those who continued to receive warfarin (non-switchers). We identified medications known or suspected to have clinically significant interactions with NOACs or warfarin. We used multivariate logistic regression, negative binomial, and generalized linear models to evaluate the influence of switching to NOACs and of potential DDIs on inpatient visits, outpatient visits, number of outpatient visits, and non-drug medical expenditures. Inverse probability of treatment weighting was also applied in analyses. Results A total of 4126 patients with AF were included in the study. Switching to NOACs was significantly and negatively related to the number of outpatient, inpatient, and emergency room (ER) visits and non-drug medical expenditures. When potential DDIs were included in the models, switching remained significantly associated only with reduced inpatient and outpatient visits. Notably, having at least one potential DDI was associated with an increased likelihood of ER visits and the number of outpatient visits; it was also significantly and positively associated with non-drug medical expenditures. Conclusions Relative to persistent warfarin use, switching to NOACs was associated with fewer inpatient, ER, and outpatient visits and lower non-drug costs. Potential DDIs were also strongly and positively associated with healthcare utilization and expenditures. Both are critical to consider in the management of AF in working-age adults.
      PubDate: 2018-08-25
      DOI: 10.1007/s40256-018-0296-x
  • Biomarkers of Thrombosis in ST-Segment Elevation Myocardial Infarction: A
           Substudy of the ATOLL Trial Comparing Enoxaparin Versus Unfractionated
    • Authors: Johanne Silvain; for the ATOLL Investigators; Stephen A. O’Connor; Yan Yan; Mathieu Kerneis; Marie Hauguel-Moreau; Michel Zeitouni; Pavel Overtchouk; Annick Ankri; Delphine Brugier; Eric Vicaut; Patrick Ecollan; Sophie Galier; Jean-Philippe Collet; Gilles Montalescot
      Abstract: Background The aim was to compare the peri-procedural biomarkers of coagulation and platelet activation in patients randomly allocated to intravenous enoxaparin or unfractionated heparin (UFH) in the ATOLL randomized trial (NCT00718471). Methods and Results A total of 129 patients (n = 58 enoxaparin and n = 71 UFH) admitted for ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) were included in this substudy of the ATOLL trial. Activated partial thromboplastin time ratio, anti-Xa activity, von Willebrand factor antigen, prothrombin fragment 1 + 2 (F1 + 2), thrombin–antithrombin complex (TAT), tissue factor pathway inhibitor and soluble CD40 ligand were measured at sheath insertion (T1) and at the end of the PCI (T2) and correlated with 1-month clinical outcomes. Target anticoagulation levels at T2 were more readily achieved in patients receiving enoxaparin compared to those receiving UFH (80.3 vs 18.2%, p < 0.0001). Increased levels of F1 + 2 and TAT measured at T2 were associated with the incidence of the composite ischemic endpoint (p = 0.04 and p = 0.03) and all-cause mortality (p < 0.0001 and p = 0.002). Release of F1 + 2 between T1 and T2 also predicted the composite ischemic endpoint (312 ± 513 vs 37 ± 292, p = 0.04) and net clinical outcome (185 ± 405 vs 3.2 ± 278, p = 0.03). Conclusions During primary PCI, enoxaparin achieved therapeutic levels more frequently than UFH. Higher level of thrombin generation measured at the end of the PCI procedure was associated with more frequent ischemic events.
      PubDate: 2018-08-25
      DOI: 10.1007/s40256-018-0294-z
  • FDA Approval of Angiotensin II for the Treatment of Hypotension in Adults
           with Distributive Shock
    • Authors: Fortunato Senatore; Gowraganahalli Jagadeesh; Martin Rose; Venkateswaran C. Pillai; Sudharshan Hariharan; Ququan Liu; McDowell Tzu-Yun; Mohan K. Sapru; Mary Ross Southworth; Norman Stockbridge
      Abstract: Distributive shock is a subset of shock marked by decreased systemic vascular resistance, organ hypoperfusion and altered oxygen extraction. Despite the use of intravenous fluids and either higher dose of catecholamines or other additional exogenous vasopressors to maintain blood pressure in the target range, the rate of mortality remains higher in patients with septic shock. Therefore, there is clearly an unmet need for additional safe and effective treatments. The use of angiotensin II to raise the mean arterial pressure (MAP) could provide additional therapy and the opportunity to evaluate a catecholamine-sparing effect by decreasing the dose of concomitant catecholamines while maintaining a target MAP. ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock phase 3; number, NCT02338843) was an adequate and well-controlled trial. The primary endpoint was the rate of MAP response at hour 3 of treatment with study drug, defined as either a 10-mmHg increase from baseline in MAP or a MAP of at least 75 mmHg. The secondary endpoints were changes from baseline in Sequential Organ Failure Assessment (SOFA) scores (total and cardiovascular). Mortality was an exploratory endpoint. The trial provided substantial evidence of the effectiveness of angiotensin II in raising blood pressure over placebo in patients with distributive shock, while keeping catecholamine levels constant. There was no change in the secondary endpoint of total SOFA scores relative to placebo when catecholamine use was reduced in lieu of angiotensin II treatment. There was a slight decrease in the secondary endpoint of cardiovascular SOFA score relative to placebo during the catecholamine-sparing phase, reflecting the catecholamine-sparing effect. There was a consistent trend in decreased mortality relative to placebo over the 28-day study period. Based on the agreements emanating from the special protocol assessment to assess blood pressure effects, the data from this single study supported approval of angiotensin II by the Food and Drug Administration for marketing in the USA.
      PubDate: 2018-08-25
      DOI: 10.1007/s40256-018-0297-9
  • Early and Late Stent Thrombosis in Patients with Versus Without Diabetes
           Mellitus Following Percutaneous Coronary Intervention with Drug-Eluting
           Stents: A Systematic Review and Meta-Analysis
    • Authors: Jun Yuan; Guang Ma Xu
      Abstract: Background Nowadays, drug-eluting stents (DES) are most commonly used compared with bare metal stents (BMS) since the former are associated with significantly lower rates of revascularization following percutaneous coronary intervention (PCI). However, unpredictable in-stent thrombosis is a major concern with DES, especially in patients with diabetes mellitus. Objective In this analysis, we aimed to systematically compare early and late stent thrombosis in patients with versus without diabetes mellitus following PCI with DES. Methods Studies were included if they were randomized controlled trials or observational studies comparing patients with diabetes mellitus versus those without it following PCI with DES and they reported acute and sub-acute/early and late stent thrombosis among their clinical outcomes. Early stent thrombosis was defined as stent thrombosis that occurred before 30 days and late stent thrombosis was defined as stent thrombosis that occurred after 30 days following PCI. The statistical analysis was carried out by the new version of the RevMan software (version 5.3), and odds ratios (ORs) and 95% confidence intervals (CIs) were considered as the statistical parameters. Results A total number of 18,910 patients were included in this analysis comparing early and late stent thrombosis in patients with diabetes mellitus (5123 patients) and in patients without diabetes mellitus (13,787 patients). Both groups of patients had similar rates of early stent thrombosis, with an OR of 1.30 (95% CI 0.89–1.91; P = 0.18, I2 = 9%) (4962 patients with diabetes mellitus were compared with 13,392 patients without diabetes mellitus). However, late stent thrombosis was significantly higher in patients with diabetes mellitus, with an OR of 1.95 (95% CI 1.35– 2.81; P = 0.0004, I2 = 0%) (5113 patients with diabetes mellitus and 13,775 patients without diabetes mellitus were compared). Conclusions Both patients with and without diabetes mellitus had a similar rate of early stent thrombosis following PCI with DES. However, diabetes mellitus was associated with a significantly higher rate of late stent thrombosis.
      PubDate: 2018-08-22
      DOI: 10.1007/s40256-018-0295-y
  • Patients’ Priorities for Oral Anticoagulation Therapy in Non-valvular
           Atrial Fibrillation: a Multi-criteria Decision Analysis
    • Authors: Marieke G. M. Weernink; Melissa C. W. Vaanholt; Catharina G. M. Groothuis-Oudshoorn; Clemens von Birgelen; Maarten J. IJzerman; Janine A. van Til
      Abstract: Introduction Effectiveness of oral anticoagulants (OACs) is critically dependent on patients’ adherence to intake regimens. We studied the relative impact of attributes related to effectiveness, safety, convenience, and costs on the value of OAC therapy from the perspective of patients with non-valvular atrial fibrillation. Methods Four attributes were identified by literature review and expert interviews: effectiveness (risk of ischemic stroke), safety (risk of major bleeding, minor bleeding, gastrointestinal complaints), convenience (intake frequency, diet restrictions, international normalized ratio [INR] blood monitoring, pill type/intake instructions), and out-of-pocket costs. Focus groups were held in Spain, Germany, France, Italy and the United Kingdom (N = 48) to elicit patients’ preferences through the use of the analytical hierarchy process method. Results Effectiveness (60%) and side effects (27%) have a higher impact on the perceived value of OACs than drug convenience (7%) and out-of-pocket costs (6%). As for convenience, eliminating monthly INR monitoring was given the highest priority (40%), followed by reducing diet restrictions (27%), reducing intake frequency (17%) and improving the pill type/intake instructions (15%). The most important side effect was major bleeding (75%), followed by minor bleeding (15%) and gastrointestinal complaints (10%). Furthermore, 71% of patients preferred once-daily intake to twice-daily intake. Discussion Although the relative impact of convenience on therapy value is small, patients have different preferences for options within convenience criteria. Besides considerations on safety and effectiveness, physicians should also discuss attributes of convenience with patients, as it can be assumed that alignment to patient preferences in drug prescription and better patient education could result in higher adherence.
      PubDate: 2018-08-22
      DOI: 10.1007/s40256-018-0293-0
  • Association Between High-Dose Spironolactone and Decongestion in Patients
           with Acute Heart Failure: An Observational Retrospective Study
    • Authors: Chris J. Kapelios; Maria Bonou; Paraskevi Vogiatzi; George Tzanis; Polyxeni Mantzouratou; Lars H. Lund; John Barbetseas
      Abstract: Background Acute congestive heart failure (ACHF) is a state of severe, secondary hyperaldosteronism. Relief of congestion has prognostic implications. Our aim was to assess associations between high-dose spironolactone and (1) decongestion and (2) safety in patients with ACHF. Methods The charts of 20 patients who were hospitalized with ACHF and received high doses of spironolactone (75–300 mg daily, group A) on top of standard of care (SOC) treatment were retrospectively studied and compared with the ones of 20 matched patients who received SOC treatment alone (group B). Results The two groups were similar as per their baseline characteristics. Mean daily spironolactone dose was 143 ± 56 in group A vs. 25 ± 25 mg in group B (P < 0.001). Patients of group A demonstrated significantly greater daily urine output (median [25th, 75th percentile] 2.9 [2.3, 3.9] vs. 2.2 [1.9, 2.5] L/day, P = 0.009), daily weight loss (1.1 [0.9, 1.7] vs. 0.4 [0.2, 1.2] kg/day, P = 0.005) and total body weight loss (10.5 [7.3, 13.8] vs. 3.8 [3.0, 6.0] kg, P < 0.001) compared with patients of group B. There were no differences in incidence of renal dysfunction, hypokalemia and hyperkalemia. Conclusion In patients with ACHF, administration of high doses of spironolactone on top of SOC treatment appears safe and is associated with greater decongestion than SOC alone.
      PubDate: 2018-07-03
      DOI: 10.1007/s40256-018-0290-3
  • Acute Coronary Syndrome in Cancer Patients
    • Authors: Begum Yetis Sayin; Mehmet Ali Oto
      Abstract: Cardiologists are seeing an increasing number of oncology patients every day, and acute coronary syndrome (ACS) is one of the problems patients encounter during follow-up. Cardio-oncology is the care of patients with cancer and cardiovascular disease, whether overt or occult, already established or acquired during treatment. Cardiovascular complications can occur acutely during or shortly after treatment and persist as long-term effects for months to years after treatment. As a delayed effect of cancer treatment, cardiovascular damage can occur months to years after the initial treatment. Vasospasm, thrombosis, and radiation-induced cardiovascular diseases can all cause ACS. Careful surveillance of ACS symptoms and regular screening during follow-up of patients with malignancy are suggested. In this review, we summarize the ACS we usually encounter during a range of cancer treatments or post cancer survival by providing illustrative case examples.
      PubDate: 2018-06-22
      DOI: 10.1007/s40256-018-0286-z
  • Cost-Effectiveness Analysis of Sacubitril-Valsartan Compared with
           Enalapril in Patients with Heart Failure with Reduced Ejection Fraction in
    • Authors: Rungroj Krittayaphong; Unchalee Permsuwan
      Abstract: Background Sacubitril-valsartan is a new medication that has recently been recommended as a replacement for enalapril in the treatment of patients with heart failure with reduced ejection fraction (HFrEF). Objective This study aimed to determine the cost effectiveness of sacubitril-valsartan compared with enalapril. Methods An analytical decision model was developed to estimate the long-term costs and outcomes from a healthcare perspective. Clinical inputs were mostly derived from the PARADIGM-HF study. Enalapril-related costs, risk of non-cardiovascular death, and all-cause readmission rate were based on data from Thailand. The costs and outcomes were discounted at 3% annually. The incremental cost-effectiveness ratio (ICER) was calculated and presented for the year 2017. A series of sensitivity analyses were also performed. Results For the base-case, the increased cost (144,146 vs. 16,048 Thai baht [THB]) of sacubitril-valsartan was associated with gains in both life-years (9.214 vs. 8.367 years) and quality-adjusted life-years (QALYs) (7.698 vs. 6.909) compared with enalapril, yielding an ICER of 162,276 THB/QALY ($US4857.11/QALY). This ICER is not considered to be cost effective at the willingness-to-pay (WTP) level of 160,000 THB/QALY. The risk of cardiovascular death and costs of both sacubitril-valsartan and hospitalization influenced the ICER. At a WTP of 160,000 THB/QALY, sacubitril-valsartan had a 48% probability of being a cost-effective treatment. Conclusions At its current price in Thailand, sacubitril-valsartan may not represent good value for the nations’s limited healthcare resources. The cost of sacubitril-valsartan needs to reduce by approximately 2% to yield an ICER below the threshold.
      PubDate: 2018-06-21
      DOI: 10.1007/s40256-018-0288-x
  • Self-Reported Non-adherence to Medication in Japanese Patients with
           Cardiovascular Diseases
    • Authors: Tsuyoshi Suzuki; Tsuyoshi Shiga; Hisako Omori; Fujio Tatsumi; Katsuji Nishimura; Nobuhisa Hagiwara
      Abstract: Objective Non-adherence to medication is an important problem in cardiovascular treatment. The aim of this study was to assess self-reported non-adherence in Japanese patients with cardiovascular disease. Methods A total of 1372 outpatients at three university hospitals who completed self-reported questionnaires were analyzed in this prospective study (mean age 67 ± 12 years; 31% female). Self-reported adherence to cardiovascular drugs was measured with a modified Siegal scale. Depressive symptoms were defined as a Patient Health Questionnaire-9 score of ≥ 10. Results A total of 227 patients (17%) were defined as non-adherent. Multiple logistic regression analysis showed that ≥ 2 times daily dosing frequency, age < 65 years and active employment were significantly associated with non-adherence, with odds ratios of 4.42 [95% confidence interval (CI) 3.02–6.48], 1.70 (95% CI 1.23–2.35) and 1.43 (95% CI 1.03–1.99), respectively. However, depression was not a significant factor in non-adherence. Conclusions Our study showed that self-reported non-adherence to medications was 17% in Japanese patients with cardiovascular disease in the university hospital setting. Daily dosing frequency, younger age and employment were significantly associated with non-adherence. Trial Registration University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) no. UMIN 000023514.
      PubDate: 2018-05-11
      DOI: 10.1007/s40256-018-0278-z
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