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Publisher: Springer-Verlag (Total: 2351 journals)

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Showing 1 - 200 of 2351 Journals sorted alphabetically
3D Printing in Medicine     Open Access  
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: 14, 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: 23, 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: 26, 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: 6, SJR: 0.24, CiteScore: 1)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 2, SJR: 0.305, 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 Parasitologica     Hybrid Journal   (Followers: 10, SJR: 0.641, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 14, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 7, 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: 51, 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: 29, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 43, 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: 5, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Hybrid Journal   (Followers: 19, 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: 28, 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: 10, 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: 3, 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: 6, 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: 63, 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: 23, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 1)
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: 8, SJR: 0.186, CiteScore: 1)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 2, 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: 142, 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: 5, 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: 14, 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: 5, 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  [2351 journals]
  • Pulmonary Arterial Hypertension: Combination Therapy in Practice
    • Authors: Marsha Burks; Simone Stickel; Nazzareno Galiè
      Pages: 249 - 257
      Abstract: Combination therapy is now regarded as the standard of care in pulmonary arterial hypertension (PAH) and is becoming widely used in clinical practice. Given the inherent complexities of combining medications, there is a need for practical advice on implementing this treatment strategy in the clinic. Drawing on our experience and expertise, within this review, we discuss some of the challenges associated with administration of combination therapy in PAH and how these can be addressed in the clinic. Despite their differing modes of action, all of the currently available classes of PAH therapy induce systemic vasodilation. In initial combination therapy regimens in particular, this may lead to additive side effects and reduced tolerability compared with monotherapy. However, approaches such as staggered treatment initiation and careful up-titration may reduce the risk of additive side effects and have been used successfully in clinical practice, as well as in clinical trials and registry studies. When combination therapy regimens are initiated, it is important that patients are monitored regularly for the presence of any side effects and that these are then managed promptly and appropriately. For patients to attain the best outcomes, the treatment regimen must be tailored to the individual’s specific needs, including consideration of PAH etiology, the presence of comorbidities and concomitant medications beyond PAH therapy, and patient lifestyle and preference. It is also vital that individuals are managed at expert care centers, where multidisciplinary teams have a wealth of specialist experience in treating PAH patients. Adherence to therapy can be a concern in a chronic disease such as PAH, and as treatment regimens become increasingly complex, maintaining good treatment adherence may become more challenging. It is essential that patients are educated on the importance of treatment adherence, and this is a key role for the PAH nurse specialist. For patients who are managed carefully in expert centers with combination therapy regimens that are tailored to their specific needs, a favorable benefit–risk ratio can be achieved. With individual and carefully managed approaches, the excellent results observed with combination therapy in clinical trials can be obtained by patients in a real-world setting.
      PubDate: 2018-08-01
      DOI: 10.1007/s40256-018-0272-5
      Issue No: Vol. 18, No. 4 (2018)
  • A Literature Review of Genetic Markers Conferring Impaired Response to
           Cardiovascular Drugs
    • Authors: Hitesh Shukla; Jessica Louise Mason; Abdullah Sabyah
      Pages: 259 - 269
      Abstract: Pharmacogenetics is an emerging area of medicine, and more work is needed to fully integrate it into a clinical setting for the benefit of patients. Genetic markers can influence the action of many drugs, including those that prevent and treat cardiovascular conditions. Genotyping is not yet commonplace, but guidelines are being put in place to help practitioners determine the effect a genetic marker may have on certain drugs. With advancements in genetic technology and falling costs, genotyping could be available to all patients via a simple saliva test. This would be a cost-effective way for practitioners to determine the most effective treatment for individuals, reducing “trial and error,” adverse effects, and rehospitalization rates and increasing patient compliance. Cardiovascular diseases are the leading causes of death worldwide, so using the most effective medication to treat or prevent them is of utmost importance in reducing incidence and mortality.
      PubDate: 2018-08-01
      DOI: 10.1007/s40256-018-0267-2
      Issue No: Vol. 18, No. 4 (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)
  • A Systematic Review on the Protective Effect of N -Acetyl Cysteine Against
           Diabetes-Associated Cardiovascular Complications
    • Authors: Phiwayinkosi V. Dludla; Stephanie C. Dias; Nnini Obonye; Rabia Johnson; Johan Louw; Bongani B. Nkambule
      Pages: 283 - 298
      Abstract: Introduction Heart failure is the leading cause of death in patients with diabetes. No treatment currently exists to specifically protect these patients at risk of developing cardiovascular complications. Accelerated oxidative stress-induced tissue damage due to persistent hyperglycemia is one of the major factors implicated in deteriorated cardiac function within a diabetic state. N-acetyl cysteine (NAC), through its enhanced capacity to endogenously synthesize glutathione, a potent antioxidant, has displayed abundant health-promoting properties and has a favorable safety profile. Objective An increasing number of experimental studies have reported on the strong ameliorative properties of NAC. We systematically reviewed the data on the cardioprotective potential of this compound to provide an informative summary. Methods Two independent reviewers systematically searched major databases, including PubMed, Cochrane Library, Google scholar, and Embase for available studies reporting on the ameliorative effects of NAC as a monotherapy or in combination with other therapies against diabetes-associated cardiovascular complications. We used the ARRIVE and JBI appraisal guidelines to assess the quality of individual studies included in the review. A meta-analysis could not be performed because the included studies were heterogeneous and data from randomized clinical trials were unavailable. Results Most studies support the ameliorative potential of NAC against a number of diabetes-associated complications, including oxidative stress. We discuss future prospects, such as identification of additional molecular mechanisms implicated in diabetes-induced cardiac damage, and highlight limitations, such as insufficient studies reporting on the comparative effect of NAC with common glucose-lowering therapies. Information on the comparative analysis of NAC, in terms of dose selection, administration mode, and its effect on different cardiovascular-related markers is important for translation into clinical studies. Conclusions NAC exhibits strong potential for the protection of the diabetic heart at risk of myocardial infarction through inhibition of oxidative stress. The effect of NAC in preventing both ischemia and non-ischemic-associated cardiac damage is also of interest. Consistency in dose selection in most studies reported remains important in dose translation for clinical relevance.
      PubDate: 2018-08-01
      DOI: 10.1007/s40256-018-0275-2
      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)
  • Drug-Eluting Stents for Treatment of Peripheral Artery Disease
    • Authors: Kazeen Abdullah; Bassel Bou Dargham; Micah Steinbrecher; Bo Sun; Zhao Huiqiang; Houman Khalili; Emmanouil S. Brilakis; Subhash Banerjee
      Pages: 175 - 180
      Abstract: Endovascular intervention is a mainstay treatment of peripheral artery disease (PAD) in addition to aggressive risk factor modification and exercise programs in patients with favorable anatomy or in those who are considered too high risk for surgical intervention. Treatment with percutaneous transluminal angioplasty (PTA) and bare metal stents (BMS) has been limited by high rates of in-stent restenosis (ISR) requiring repeat revascularization. Drug-eluting stents (DES), developed and designed to reduce ISR, offer a promising solution to the current challenges in endovascular management of PAD. Several randomized clinical trials have shown improved short- and mid-term outcomes with DES as compared with both PTA and BMS. Herein we provide an up-to-date review of the current literature on DES use in PAD.
      PubDate: 2018-06-01
      DOI: 10.1007/s40256-018-0265-4
      Issue No: Vol. 18, No. 3 (2018)
  • A Database Cohort Study to Assess the Risk of Angioedema Among Patients
           with Heart Failure Initiating Angiotensin-Converting Enzyme Inhibitors in
           the USA
    • Authors: Thy P. Do; Arpamas Seetasith; Rossella Belleli; Raymond G. Schlienger; Stefano Corda; Chakkarin Burudpakdee; Hendrik J. Streefkerk; Sigrid Behr
      Pages: 205 - 211
      Abstract: Introduction Real-world evidence on the risk of angioedema associated with angiotensin-converting enzyme inhibitors (ACEIs) in patients with heart failure (HF) is scarce. Objective This non-interventional study aimed to estimate the incidence of and risk factors for angioedema in patients with HF initiating an ACEI in real-world practice. Methods This was a retrospective cohort study using claims data from the PharMetrics Plus database, supplemented with consumer health data, from 1 January 2007 to 31 March 2015. Patients with HF initiating an ACEI were followed up for a maximum of 1 year, until the first occurrence of angioedema or until cohort exit. Angioedema incidence rates were estimated and stratified by potential risk factors such as race, age, sex, and time from initiation of ACEI therapy. For each risk factor, the unadjusted and adjusted hazard ratio (HR) was calculated; exploratory analyses were carried out to account for all potential confounders. Results We identified 21,639 patients with HF initiating an ACEI (mean age 58 years; 35.6% women; mean follow-up 205 days). The 1-year incidence of angioedema per 1000 patient-years was 3.3 [95% confidence interval (CI) 2.4–4.5]. The incidence was higher in Black [6.2 (95% CI 3.1–12.5)] than in non-black [2.9 (95% CI 2.1–4.1)] patients, higher in women [5.2 (95% CI 3.4–7.9)] than in men [2.3 (95% CI 1.5–3.6)], and greatest in the first 30 days of ACEI therapy. Conclusions The risk of angioedema in patients with HF initiating an ACEI observed in this study is in line with published estimates for the general patient population treated with ACEIs.
      PubDate: 2018-06-01
      DOI: 10.1007/s40256-017-0256-x
      Issue No: Vol. 18, No. 3 (2018)
  • Protection from Reperfusion Injury with Intracoronary N -Acetylcysteine in
           Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention
           in a Cardiac Tertiary Center
    • Authors: Younes Nozari; Azadeh Eshraghi; Azita Hajhossein Talasaz; Mostafa Bahremand; Jamshid Salamzadeh; Mojtaba Salarifar; Hamidreza Pourhosseini; Arash Jalali; Seyedeh Hamideh Mortazavi
      Pages: 213 - 221
      Abstract: Background Evidence suggests that oxidative stress plays a principal role in myocardial damage following ischemia/reperfusion events. Recent studies have shown that the antioxidant properties of N-acetylcysteine (NAC) may have cardioprotective effects in high doses, but—to the best of our knowledge—few studies have assessed this. Objectives Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury. Methods We conducted a randomized double-blind placebo-controlled trial in which 100 consecutive patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly assigned to the case group (high-dose NAC 100 mg/kg bolus followed by intracoronary NAC 480 mg during PCI then intravenous NAC 10 mg/kg for 12 h) or the control group (5% dextrose). We measured differences in peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction frame count (cTFC). Results The peak CK-MB level was comparable between the two groups (P = 0.327), but patients receiving high-dose NAC demonstrated a significantly larger reduction in hs-TnT (P = 0.02). In total, 94% of the NAC group achieved TIMI flow grade 3 versus 80% of the control group (P = 0.03). No significant differences were observed between the two groups in terms of changes in the cTFC and MBG. Conclusions In this study, NAC improved myocardial reperfusion markers and coronary blood flow, as revealed by differences in peak hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large samples are warranted to elucidate the role of NAC in this population. identifier: NCT01741207, and the Iranian Registry of Clinical Trials (IRCT; registration number: IRCT201301048698N8.
      PubDate: 2018-06-01
      DOI: 10.1007/s40256-017-0258-8
      Issue No: Vol. 18, No. 3 (2018)
  • Comparison of Warfarin Requirements in Post-cardiac Surgery Patients:
           Valve Replacement Versus Non-valve Replacement
    • Authors: Logan M. Olson; Andrea M. Nei; David L. Joyce; Narith N. Ou; Ross A. Dierkhising; Scott D. Nei
      Pages: 223 - 229
      Abstract: Introduction Anticoagulation with warfarin affects approximately 140,000 post-cardiac surgery patients every year, yet there remains limited published data in this patient population. Dosing remains highly variable due to intrinsic risk factors that plague cardiac surgery candidates and a lack of diverse literature that can be applied to those who have undergone a cardiac surgery alternative to heart valve replacement (HVR). In the present study, our aim was to compare the warfarin requirements between HVR and non-HVR patients. Methods This was a single-center, retrospective study of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October 31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac surgeries. Results A total of 683 patients were assessed during the study period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A multivariable analysis was performed to adjust for gender, age, body mass index and drug interactions. Conclusions This was the largest study to evaluate warfarin dose requirements in post-cardiac surgery patients and is the first to compare warfarin requirements between HVR and non-HVR patients during the immediate post-operative period. Both groups had similar warfarin requirements, which supports expanding the initial warfarin dosing recommendations of the 9th edition Chest guideline to include non-HVR patients as well as HVR patients.
      PubDate: 2018-06-01
      DOI: 10.1007/s40256-017-0261-0
      Issue No: Vol. 18, No. 3 (2018)
  • 67th Annual Scientific Sessions of the American College of Cardiology:
           10–12 March 2018; Orlando, FL, USA
    • Authors: Amitabh Prakash
      Pages: 245 - 248
      PubDate: 2018-06-01
      DOI: 10.1007/s40256-018-0281-4
      Issue No: Vol. 18, No. 3 (2018)
  • Oral Antiplatelet Therapy for Secondary Prevention of Acute Coronary
    • Authors: Jeffrey S. Berger
      Abstract: Patients surviving an acute coronary syndrome (ACS) remain at increased risk of ischemic events long term. This paper reviews current evidence and guidelines for oral antiplatelet therapy for secondary prevention following ACS, with respect to decreased risk of ischemic events versus bleeding risk according to individual patient characteristics and risk factors. Specifically, data are reviewed from clinical studies of clopidogrel, prasugrel, ticagrelor and vorapaxar, as well as the results of systematic reviews and meta-analyses looking at the benefits and risks of oral antiplatelet therapy, and the relative merits of shorter versus longer duration of dual antiplatelet therapy, in different patient groups.
      PubDate: 2018-07-10
      DOI: 10.1007/s40256-018-0291-2
  • 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
  • Neprilysin Inhibitors: Filling a Gap in Heart Failure Management, Albeit
           Amidst Controversy and at a Significant Cost
    • Authors: Antonis S. Manolis; Theodora A. Manolis; Antonis A. Manolis; Helen Melita
      Abstract: Dual angiotensin and neprilysin inhibition using the combination drug sacubitril–valsartan has ushered in a new era in the treatment of heart failure (HF). The randomized controlled PARADIGM-HF trial, which randomized 8399 patients with HF to enalapril or sacubitril–valsartan, showed a 20% reduction in mortality and HF hospitalization with the new drug. This has been heralded as a step toward filling a crucial gap in HF management by providing strong evidence that combined inhibition of the angiotensin receptor and neprilysin is superior to inhibition of the renin–angiotensin system alone in stable patients with chronic HF as it negates the deleterious effects of angiotensin while concomitantly augmenting the beneficial effects of the endogenous natriuretic peptide system. This new therapy is costly, and other confirmatory studies have been lacking for over 2 years since its approval by major regulatory authorities. As such, controversy and heated discussions have amassed, as has detailed information from a plethora of secondary analyses of this pivotal trial about the pros and cons of this promising new therapeutic strategy in HF management. The aim of this review was to provide a critical assessment of all these aspects.
      PubDate: 2018-06-20
      DOI: 10.1007/s40256-018-0289-9
  • Antithromboembolic Strategies for Patients with Atrial Fibrillation
           Undergoing Percutaneous Coronary Intervention
    • Authors: Ayesha Ather; Benjamin Laliberte; Brent N. Reed; Ashley Schenk; Kristin Watson; Sandeep Devabhakthuni; Vincent Y. See
      Abstract: We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6–12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y12 inhibitor used. Each category review was followed by a discussion providing insight into the quality of evidence and implications for practice. We found that the risk of bleeding with TT was higher than with DT, without demonstrated added benefit of reducing major adverse cardiovascular events. TT use should be minimized in patients with high bleeding risk, and patient-specific factors should be critically analyzed to select appropriate antiplatelet and anticoagulant agents.
      PubDate: 2018-06-19
      DOI: 10.1007/s40256-018-0287-y
  • 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
      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: 2018-06-13
      DOI: 10.1007/s40256-018-0284-1
  • 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
  • Comparing the Cost Effectiveness of Non-vitamin K Antagonist Oral
           Anticoagulants with Well-Managed Warfarin for Stroke Prevention in Atrial
           Fibrillation Patients at High Risk of Bleeding
    • Authors: Alexa R. Hospodar; Kenneth J. Smith; Yuting Zhang; Inmaculada Hernandez
      Abstract: Background Several studies have compared the cost effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin using results from clinical trials evaluating NOACs. However, the time in therapeutic range (TTR) of warfarin groups ranged across clinical trials, and all were below the therapeutic goal of 70%. We compared the cost effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg, and well-managed warfarin with a TTR of 70% in preventing stroke among patients with atrial fibrillation at high risk of bleeding. Methods For the six treatments, we used a Markov state-transition model to quantify lifetime costs in $US and effectiveness in quality-adjusted life-years (QALYs). We simulated relative risk ratios of clinical events with each NOAC versus warfarin with a TTR of 70% using published regression models that predict how the incidence of thrombotic or hemorrhagic events changes for each unit change in TTR. We re-ran our analysis for two other estimates of TTR: 65 and 75%. Results Treatment with edoxaban 60 mg cost $US127,520/QALY gained compared with warfarin with a TTR of 70% and cost $US41,860/QALY gained compared with warfarin with a TTR of 65%. However, warfarin with a TTR of 75% was more effective and less expensive than all NOACs. For three levels of TTR, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, and rivaroxaban 20 mg were dominated strategies. Conclusions The comparative cost effectiveness of edoxaban and warfarin is highly sensitive to TTR. At the $US100,000/QALY willingness-to-pay threshold, our results suggest that warfarin is the most cost-effective treatment for patients who can achieve a TTR of 70%.
      PubDate: 2018-05-09
      DOI: 10.1007/s40256-018-0279-y
  • Association of Beta-Blockers with Survival on Patients Presenting with ACS
           Treated with PCI: A Propensity Score Analysis from the BleeMACS Registry
    • Authors: Fabrizio D’Ascenzo; Dario Celentani; Alessandro Brustio; Alberto Grosso; Sergio Raposeiras-Roubín; Emad Abu-Assi; Jose Paulo Simao Henriques; Jorge Saucedo; José Ramón González-Juanatey; Stephen B. Wilton; Wouter J. Kikkert; Iván Nuñez-Gil; Albert Ariza-Sole; Xiantao Song; Dimitrios Alexopoulos; Christoph Liebetrau; Tetsuma Kawaji; Zenon Huczek; Shao-Ping Nie; Toshiharu Fujii; Luis Correia; Masa-aki Kawashiri; José María García-Acuña; Danielle Southern; Emilio Alfonso; Belén Terol; Alberto Garay; Dongfeng Zhang; Yalei Chen; Ioanna Xanthopoulou; Neriman Osman; Helge Möllmann; Hiroki Shiomi; Michal Kowara; Krzysztof Filipiak; Xiao Wang; Yan Yan; Jing-Yao Fan; Yuji Ikari; Takuya Nakahayshi; Kenji Sakata; Masakazu Yamagishi; Oliver Kalpak; Sasko Kedev; Claudio Moretti; Maurizio D’Amico; Fiorenzo Gaita
      Abstract: Purpose The aim was to evaluate prognostic value of beta-blocker (BB) administration in acute coronary syndromes (ACS) patients in the percutaneous coronary intervention (PCI) era. Methods and Results The BleeMACS project is a multicenter, observational, retrospective registry enrolling patients with ACS worldwide in 15 hospitals. Patients discharged with BB therapy were compared to those discharged without a BB before and after propensity score with matching. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included in-hospital reinfarction, in-hospital heart failure, 1-year myocardial infarction, 1-year bleeding and 1-year composite of death and recurrent myocardial infarction. After matching, 2935 patients for each group were enrolled. The primary endpoint of 1-year death was significantly lower in the group on BB therapy (4.5 vs 7%, p < 0.05), while only a trend was noted for recurrent acute myocardial infarction (4.5 vs 4.9%, p = 0.54). These results were consistent for patients older than 80 years of age, for ST-elevation myocardial infarction (STEMI) patients, and for those discharged with complete versus incomplete revascularization, but not for non-STEMI/unstable angina patients. Conclusions BB therapy was related to 1-year lower risk of all-cause mortality, independently from completeness of revascularization, admission diagnosis, age and ejection fraction. Randomized controlled trials for patients treated with PCI for ACS should be performed.
      PubDate: 2018-04-24
      DOI: 10.1007/s40256-018-0273-4
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