Economic Burden Associated with the Treatment with a Cardiovascular Polypill in Secondary Prevention in Spain: Cost-Effectiveness Results of the NEPTUNO Study

Alberto Cordero,1,2 Regina Dalmau González-Gallarza,3 Lluis Masana,4– 6 Valentín Fuster,7,8 Jose Mª Castellano,7,9,10 José Emilio Ruiz Olivar,11 Ilonka Zsolt,11 Antoni Sicras-Mainar,12 Jose Ramón González Juanatey2,13,14 1Cardiology Service, San Juan University Hospital, Alicante, Spain; 2Cardiovascular Diseases Network Research Center (CIBERCV), Madrid, Spain; 3Cardiology Service, La Paz University Hospital, Madrid, Spain; 4Sant Joan University Hospital, Vascular Medicine and Metabolism Unit, Reus, Spain; 5Pere Virgili Institute of Health Research (IISPV), Reus, Spain; 6Center for Biomedical Research Network on Diabetes and Associated Metabolic Diseases (CIBERDEM), Reus, Spain; 7National Center for Cardiovascular Research (CNIC), Carlos III Health Institute, Madrid, Spain; 8Mount Sinai Medical Center, New York, NY, USA; 9Integral Center for Cardiovascular Diseases (CIEC), Montepríncipe University Hospital, HM Hospitales Group, Madrid, Spain; 10School of Medicine, CEU San Pablo University, Madrid, Spain; 11Corporate Medical Affairs, Ferrer, Barcelona, Spain; 12Health Economics and Outcomes Research Department, Atrys Health, Madrid, Spain; 13Cardiology Service, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 14Santiago de Compostela Health Research Institute (IDIS), Santiago de Compostela, SpainCorrespondence: Antoni Sicras-Mainar, Atrys Health SA, Calle Príncipe de Vergara, 132, planta 1, Madrid, 28002, Spain, Tel +34 917 819 465, Fax +34 915 776 744, Email [email protected]: The aim of this study was to estimate health-care resources utilization, costs and cost-effectiveness associated with the treatment with CNIC-Polypill as secondary prevention of atherosclerotic cardiovascular disease (ASCVD) compared to other treatments, in clinical practice in Spain.Patients and Methods: An observational, retrospective study was performed using medical records (economic results [healthcare perspective], NEPTUNO-study; BIG-PAC-database) of patients who initiated secondary prevention between 2015 and 2018. Patients were followed up to 2 years (maximum). Four cohorts were balanced with a propensity-score-matching (PSM): 1) CNIC-Polypill (aspirin+atorvastatin+ramipril), 2) Monocomponents (same separate drugs), 3) Equipotent (equipotent drugs) and 4) Other therapies ([OT], other cardiovascular drugs). Incidence of cardiovascular events, health-care resources utilization and healthcare and non-healthcare costs (2020 Euros) were compared. Incremental cost-effectiveness ratios per cardiovascular event avoided were estimated.Results: After PSM, 1614 patients were recruited in each study cohort. The accumulated incidence of cardiovascular events during the 24-month follow-up was lower in the CNIC-Polypill cohort vs the other cohorts (19.8% vs Monocomponents: 23.3%, Equipotent: 25.5% and OT: 26.8%; p< 0.01). During the follow-up period, the CNIC-Polypill cohort also reduced the health-care resources utilization per patient compared to the other cohorts, particularly primary care visits (16.6 vs Monocomponents: 18.7, Equipotent: 18.9 and OT: 21.0; p< 0.001) and hospitalization days (2.3 vs Monocomponents: 3.4, Equipotent: 3.7 and OT: 4.0; p< 0.001). The treatment cost in the CNIC-Polypill cohort was lower than that in the other cohorts (€ 4668 vs Monocomponents: € 5587; Equipotent: € 5682 and OT: € 6016; p< 0.001) (Difference: -€ 919, -€ 1014 and -€ 1348, respectively). Due to the reduction of cardiovascular events and costs, the CNIC-Polypill is a dominant alternative compared to the other treatments.Conclusion: CNIC-Polypill reduces recurrent major cardiovascular events and costs, being a cost-saving strategy as secondary prevention of ASCVD.Keywords: secondary prevention, cardiovascular events, use of healthcare resources, healthcare costs, Spain, CNIC-polypil

Detection of high cardiovascular risk patients with ankylosing spondylitis based on the assessment of abdominal aortic calcium as compared to carotid ultrasound

ABSTRACT: Background: This study aimed to determine whether, besides carotid ultrasound (US), a lateral lumbar spine radiography may also help identify ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. Methods: A set of 125 AS patients older than 35 years without a history of CV events, diabetes mellitus, or chronic kidney disease was recruited. Carotid US and lateral lumbar spine radiography were performed in all of them. The CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC- CORE) algorithm. Presence of carotid plaques was defined following the Mannheim Carotid Intima-media Thickness and Plaque Consensus. Abdominal aortic calcium (AAC) in a plain radiography was defined as calcific densities visible in an area parallel and anterior to the lumbar spine. Results: Carotid US showed higher sensitivity than lateral lumbar spine radiography to detect high CV risk in the 54 patients with moderate TC-SCORE (61% versus 38.9%). Using carotid plaques as the gold standard test, a predictive model that included a TC-SCORE >= 5% or the presence of AAC in the lateral lumbar spine radiography in patients with both moderate and low CV risk (< 5%) according to the TC-SCORE yielded a sensitivity of 50.9% with a specificity of 95.7% to identify high/very high CV-risk AS patients. A positive correlation between AAC and carotid plaques was observed (r2 = 0.49, p < 0.001). Conclusions: A lateral lumbar spine radiography is a useful tool to identify patients with AS at high risk of CV disease

ESC core curriculum for the general cardiologist (2013)

[No abstract available

Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI)

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3–7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI

PERFORMA AKUSTIK PADA RUANG MUSIK DI SEKOLAH LUAR BIASA NEGERI MARAWOLA KABUPATEN SIGI

Ruang musik dengan menggunakan bahan isolasi bunyi dari glasswool yang dipadukan dengan beberapa bahan bangunan, seperti tripleks, hardboard dan dinding bata, serta desain tata letak ruang dan bukaan yang spesifik sesuai dengan aturan performa akustik pada umumnya, dimana akan dibahas eksplorasi desain akustik dengan pendekatan analisa pengaruh level/tingkatan suara.Hasil penelitian menunjukkan bahwa kajian performa level suara dan performa akuistik menunjukkan hasil yang signifikan yaitu mampu menghilangkan dengung dalam ruang sehingga menghasilkan suara musik yang baik dalam ruang dan mampu menahan rambatan bunyi poda lingkungan sekitarnya sehingga keberadaan ruang musik di Sekolah Luar Biasa Marawola tersebut tidak menggangu aktifitas belajar-mengajar pada ruang sekitarny

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC

2016 ESC on Acute and Chronic H

Protein inhibitor of NOS1 plays a central role in the regulation of NOS1 activity in human dilated hearts

An essential factor for the production of nitric oxide by nitric oxide synthase 1 (NOS1), major modulator of cardiac function, is the cofactor tetrahydrobiopterin (BH4). BH4 is regulated by GTP cyclohydrolase 1, the rate-limiting enzyme in BH4 biosynthesis which catalyses the formation of dihydroneopterin 3′triphosfate from GTP, producing BH4 after two further steps catalyzed by 6-pyruvoyltetrahydropterin synthase and sepiapterin reductase. However, there are other essential factors involved in the regulation of NOS1 activity, such as protein inhibitor of NOS1 (PIN), calmodulin, heat shock protein 90, and NOS interacting protein. All these molecules have never been analysed in human non-ischemic dilated hearts (DCM). In this study we demonstrated that the upregulation of cardiac NOS1 is not accompanied by increased NOS1 activity in DCM, partly due to the elevated PIN levels and not because of alterations in biopterin biosynthesis. Notably, the PIN concentration was significantly associated with impaired ventricular function, highlighting the importance of this NOS1 activity inhibitor in Ca2+ homeostasis. These results take a central role in the current list of targets for future studies focused on the complex cardiac dysfunction processes through more efficient harnessing of NOS1 signalling

Human ischemic cardiomyopathy shows cardiac Nos1 translocation and its increased levels are related to left ventricular performance

The role of nitric oxide synthase 1 (NOS1) as a major modulator of cardiac function has been extensively studied in experimental models; however, its role in human ischemic cardiomyopathy (ICM) has never been analysed. Thus, the objectives of this work are to study NOS1 and NOS-related counterparts involved in regulating physiological function of myocyte, to analyze NOS1 localisation, activity, dimerisation, and its relationship with systolic function in ICM. The study has been carried out on left ventricular tissue obtained from explanted human hearts. Here we demonstrate that the upregulation of cardiac NOS1 is not accompanied by an increase in NOS activity, due in part to the alterations found in molecules involved in the regulation of its activity. We observed partial translocation of NOS1 to the sarcolemma in ischemic hearts, and a direct relationship between its protein levels and systolic ventricular function. Our findings indicate that NOS1 may be significant in the pathophysiology of human ischemic heart disease with a preservative role in maintaining myocardial homeostasis