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Bicocca Open Archive
Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4–1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20–2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25–2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78–2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65–2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, −0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89–1·11). HRs were 0·97 (95% CI 0·87–1·09) for patients with prediabetes and 1·30 (95% CI 0·93–1·81) for those with normoglycaemia (pinteraction=0·11). Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65–1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes.
Ray, K., Colhoun, H., Szarek, M., Baccara-Dinet, M., Bhatt, D., Bittner, V., et al. (2019). Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. THE LANCET DIABETES & ENDOCRINOLOGY, 7(8), 618-628 [10.1016/S2213-8587(19)30158-5].
Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial
Ray K. K.;Colhoun H. M.;Szarek M.;Baccara-Dinet M.;Bhatt D. L.;Bittner V. A.;Budaj A. J.;Diaz R.;Goodman S. G.;Hanotin C.;Harrington R. A.;Jukema J. W.;Loizeau V.;Lopes R. D.;Moryusef A.;Murin J.;Pordy R.;Ristic A. D.;Roe M. T.;Tunon J.;White H. D.;Zeiher A. M.;Schwartz G. G.;Steg P. G.;Schwartz G. G.;Steg P. G.;Bhatt D. L.;Bittner V. A.;Harrington R. A.;Jukema J. W.;Zeiher A. M.;Tricoci P.;Roe M. T.;Mahaffey K. W.;Edelberg J. M.;Lecorps G.;Sasiela W. J.;Tamby J. -F.;Aylward P. E.;Drexel H.;Sinnaeve P.;Dilic M.;Lopes R. D.;Gotcheva N. N.;Prieto J. -C.;Yong H.;Lopez-Jaramillo P.;Pecin I.;Reiner Z.;Ostadal P.;Viigimaa M.;Nieminen M. S.;Chumburidze V.;Marx N.;Danchin N.;Liberopoulos E.;Montenegro Valdovinos P. C.;Tse H. -F.;Kiss R. G.;Xavier D.;Zahger D.;Valgimigli M.;Kimura T.;Kim H. S.;Kim S. -H.;Erglis A.;Laucevicius A.;Kedev S.;Yusoff K.;Ramos Lopez G. A.;Alings M.;Halvorsen S.;Correa Flores R. M.;Morais J.;Dorobantu M.;Karpov Y.;Ristic A. D.;Chua T.;Fras Z.;Dalby A. J.;de Silva H. A.;Hagstrom E.;Landmesser U.;Chiang C. -E.;Sritara P.;Guneri S.;Parkhomenko A.;Ray K. K.;Moriarty P. M.;Vogel R.;Chaitman B.;Kelsey S. F.;Olsson A. G.;Rouleau J. -L.;Simoons M. L.;Alexander K.;Meloni C.;Rosenson R.;Sijbrands E. J. G.;Alexander J. H.;Armaganijan L.;Bagai A.;Bahit M. C.;Brennan J. M.;Clifton S.;DeVore A. D.;Deloatch S.;Dickey S.;Dombrowski K.;Ducrocq G.;Eapen Z.;Endsley P.;Eppinger A.;Harrison R. W.;Hess C. N.;Hlatky M. A.;Jordan J. D.;Knowles J. W.;Kolls B. J.;Kong D. F.;Leonardi S.;Lillis L.;Maron D. J.;Marcus J.;Mathews R.;Mehta R. H.;Mentz R. J.;Moreira H. G.;Patel C. B.;Bernardez-Pereira S.;Perkins L.;Povsic T. J.;Puymirat E.;Schuyler Jones W.;Shah B. R.;Sherwood M. W.;Stringfellow K.;Sujjavanich D.;Toma M.;Trotter C.;Van Diepen S.;Wilson M. D.;Yan A. T.;Schiavi L. B.;Garrido M.;Alvarisqueta A. F.;Sassone S. A.;Bordonava A. P.;Alves De Lima A. E.;Schmidberg J. M.;Duronto E. A.;Caruso O. C.;Novaretto L. P.;Hominal M. A.;Montana O. R.;Caccavo A.;Gomez Vilamajo O. A.;Lorenzatti A. J.;Cartasegna L. R.;Paterlini G. A.;Mackinnon I. J.;Caime G. D.;Amuchastegui M.;Salomone O.;Codutti O. R.;Jure H. O.;Bono J. O.;Hrabar A. D.;Vallejos J. A.;Ahuad Guerrero R. A.;Novoa F.;Patocchi C. A.;Zaidman C. J.;Giuliano M. E.;Dran R. D.;Vico M. L.;Carnero G. S.;Guzman P. N.;Medrano Allende J. C.;Garcia Brasca D. F.;Bustamante Labarta M. H.;Nani S.;Blumberg E. D.;Colombo H. R.;Liberman A.;Fuentealba V.;Luciardi H. L.;Waisman G. D.;Berli M. A.;Garcia Duran R. O.;Cestari H. G.;Luquez H. A.;Giordano J. A.;Saavedra S. S.;Zapata G.;Costamagna O.;Llois S.;Waites J. H.;Collins N.;Soward A.;Hii C. L.;Shaw J.;Arstall M. A.;Horowitz J.;Ninio D.;Rogers J. F.;Colquhoun D.;Oqueli Flores R. E.;Roberts-Thomson P.;Raffel O.;Lehman S. J.;Aroney C.;Coverdale S. G.;Garrahy P. J.;Starmer G.;Sader M.;Carroll P. A.;Dick R.;Zweiker R.;Hoppe U.;Huber K.;Berger R.;Delle-Karth G.;Frey B.;Weidinger F.;Faes D.;Hermans K.;Pirenne B.;Leone A.;Hoffer E.;Vrolix M. 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C.;Alonso Orcajo N.;Valdivielso P.;Constantine G.;Haniffa R.;Tissera N.;Amarasekera S.;Ponnamperuma C.;Fernando N.;Fernando K.;Jayawardena J.;Wijeyasingam S.;Ranasinghe G.;Ekanayaka R.;Mendis S.;Senaratne V.;Mayurathan G.;Sirisena T.;Rajapaksha A.;Herath J. I.;Amarasena N.;Berglund S.;Rasmanis G.;Vedin O.;Witt N.;Mourtzinis G.;Nicol P.;Hansen O.;Romeo S.;Agergaard Jensen S.;Torstensson I.;Ahremark U.;Sundelin T.;Moccetti T.;Muller C.;Mach F.;Binde R.;Tsai W. -C.;Ueng K. -C.;Lai W. -T.;Liu M. -E.;Hwang J. -J.;Yin W. -H.;Hsieh I. -C.;Hsieh M. -J.;Lin W. H.;Kuo J. -Y.;Huang T. -Y.;Fang C. -Y.;Kaewsuwanna P.;Soonfuang W.;Jintapakorn W.;Sukonthasarn A.;Wongpraparut N.;Sastravaha K.;Sansanayudh N.;Kehasukcharoen W.;Piyayotai D.;Chotnoparatpat P.;Camsari A.;Kultursay H.;Mutlu B.;Ersanli M.;Demirtas M.;Kirma C.;Ural E.;Koldas L.;Karpenko O.;Prokhorov A.;Vakaluyk I.;Myshanych H.;Reshotko D.;Batushkin V.;Rudenko L.;Kovalskyi I.;Kushnir M.;Tseluyko V.;Mostovoy Y.;Stanislavchuk M.;Kyiak Y.;Karpenko Y.;Malynovsky Y.;Klantsa A.;Kutniy O.;Amosova E.;Tashchuk V.;Leshchuk O.;Rishko M.;Kopytsya M.;Yagensky A.;Vatutin M.;Bagriy A.;Barna O. M.;Ushakov O.;Dzyak G.;Goloborodko B.;Rudenko A.;Zheleznyy V.;Trevelyan J.;Zaman A.;Lee K.;Moriarty A.;Aggarwal R. K.;Clifford P.;Wong Y. -K.;Iqbal S. M.;Subkovas E.;Braganza D.;Sarkar D.;Storey R.;Griffiths H.;McClure S.;Muthusamy R.;Smith S.;Kurian J.;Levy T.;Barr C.;Kadr H.;Gerber R.;Simaitis A.;Soran H.;Mathur A.;Brodison A.;Ayaz M.;Cheema M.;Oliver R.;Thackray S.;Mudawi T.;Rahman G.;Sultan A.;Sharman D.;Sprigings D.;Butler R.;Wilkinson P.;Lip G. Y.;Halcox J.;Gallagher S.;Ossei-Gerning N.;Vardi G.;Baldari D.;Brabham D.;Treasure II C.;Dahl C.;Palmer B.;Wiseman A.;Khan A.;Puri S.;Mohart A. E.;Ince C.;Flores E.;Wright S.;Cheng S. -C.;Rosenberg M.;Rogers W.;Kosinski E.;Forgosh L.;Waltman J.;Khan M.;Shoukfeh M.;Dagher G.;Cambier P.;Lieber I.;Kumar P.;East C.;Krichmar P.;Hasan M.;White L.;Knickelbine T.;Haldis T.;Gillespie E.;Amidon T.;Suh D.;Arif I.;Abdallah M.;Akhter F.;Carlson E.;D'Urso M.;El-Ahdab F.;Nelson W.;Moriarty K.;Harris B.;Cohen S.;Carter L.;Doty D.;Sabatino K.;Haddad T.;Malik A.;Rao S.;Mulkay A.;Jovin I.;Klancke K.;Malhotra V.;Devarapalli S. K.;Koren M.;Chandna H.;Dodds III G.;Goraya T.;Bengston J.;Janik M.;Moran J.;Sumner A.;Kobayashi J.;Davis W.;Yazdani S.;Pasquini J.;Thakkar M.;Vedere A.;Leimbach W.;Rider J.;Fenton S.;Singh N.;Shah A. V.;Janosik D.;Pepine C.;Berman B.;Gelormini J.;Daniels C.;Richard K.;Keating F.;Kondo N. I.;Shetty S.;Levite H.;Waider W.;Takata T.;Abu-Fadel M.;Shah V.;Aggarwal R.;Izzo M.;Kumar A.;Hattler B.;Do R.;Link C.;Bortnick A.;Kinzfogl III G.;Ghitis A.;Larry J.;Teufel E.;Kuhlman P.;Mclaurin B.;Zhang W.;Thew S.;Abbas J.;White M.;Islam O.;Subherwal S.;Ranadive N.;Vakili B.;Gring C.;Henderson D.;Schuchard T.;Farhat N.;Kline G.;Mahal S.;Whitaker J.;Speirs S.;Andersen R.;Daboul N.;Horwitz P.;Zahr F.;Ponce G.;Jafar Z.;Mcgarvey J.;Panchal V.;Voyce S.;Blok T.;Sheldon W.;Azizad M. M.;Schmalfuss C.;Picone M.;Pederson R.;Herzog W.;Friedman K.;Lindsey J.;Nowins R.;Timothy E.;Leonard P.;Lepor N.;El Shahawy M.;Weintraub H.;Irimpen A.;Alonso A.;May W.;Christopher D.;Galski T.;Chu A.;Mody F.;Ramin E.;Hodes Z.;Rossi J.;Rose G.;Fairlamb J.;Lambert C.;Raisinghani A.;Abbate A.;Vetrovec G.;King M.;Carey C.;Gerber J.;Younis L.;Park H. T.;Vidovich M.;Knutson T.;Friedman D.;Chaleff F.;Loussararian A.;Rozeman P.;Kimmelstiel C.;Kuvin J.;Silver K.;Foster M.;Tonnessen G.;Espinoza A.;Amlani M.;Wali A.;Malozzi C.;Jong G. T.;Massey C.;Wattanakit K.;O'Donnell P. J.;Singal D.;Jaffrani N.;Banuru S.;Fisher D.;Xenakis M.;Perlmutter N.;Bhagwat R.;Strader J.;Blonder R.;Akyea-Djamson A.;Labroo A.;Lee K.;Marais H. J.;Claxton E.;Weiss R.;Kathryn R.;Berk M.;Rossi P.;Joshi P.;Khera A.;Khaira A. S.;Kumkumian G.;Lupovitch S.;Purow J.;Welka S.;Hoffman D.;Fischer S.;Soroka E.;Eagerton D.;Pancholy S.;Ray M.;Erenrich N.;Farrar M.;Pollock S.;French W. J.;Diamantis S.;Guy D.;Gimple L.;Neustel M.;Schwartz S.;Pereira E.;Albert S.;Spriggs D.;Strain J.;Mittal S.;Vo A.;Chane M.;Hall J.;Vijay N.;Lotun K.;Lester F. M.;Nahhas A.;Pope T.;Nager P.;Vohra R.;Sharma M.;Bashir R.;Ahmed H.;Berlowitz M.;Fishberg R.;Barrucco R.;Yang E.;Radin M.;Sporn D.;Stapleton D.;Eisenberg S.;Landzberg J.;Mcgough M.;Turk S.;Schwartz M.;Sundram P. S.;Jain D.;Zainea M.;Bayron C.;Karlsberg R.;Dohad S.;Lui H.;Keen W.;Westerhausen D.;Khurana S.;Agarwal H.;Birchem J.;Penny W.;Chang M.;Murphy S.;Henry J.;Schifferdecker B.;Gilbert J. M.;Chalavarya G.;Eaton C.;Schmedtje J. F.;Christenson S.;Dotani I.;Denham D.;Macdonell A.;Gibson P.;Rahman A.;Al Joundi T.;Assi N.;Conrad G.;Kotha P.;Love M.;Giesler G.;Rubenstein H.;Gamil D.;Akright L.;Krawczyk J.;Cobler J.;Wells T.;Welker J.;Foster R.;Gilmore R.;Anderson J.;Jacoby D.;Harris B.;Gardner G.;Dandillaya R.;Vora K.;Kostis J.;Hunter J.;Laxson D.;Ball E.;Lopes R.;Egydio F.;Kawakami A.;Oliveira J.;Wozniak J.;Matthews A.;Ratky C.;Valiris J.;Berdan L.;Hepditch A.;Quintero K.;Rorick T.;Westbrook M.;Pascual A.;Rovito C.;Bezault M.;Drouet E.;Simon T.;Alsweiler C.;Luyten A.;Butters J.;Griffith L.;Shaw M.;Grunberg L.;Islam S.;Bregeault M. -F.;Bougon N.;Faustino D.;Fontecave S.;Murphy J.;Verrier M.;Agnetti V.;Andersen D.;Badreddine E.;Bekkouche M.;Bouancheau C.;Brigui I.;Brocklehurst M.;Cianciarulo J.;Devaul D.;Domokos S.;Gache C.;Gobillot C.;Guillou S.;Healy J.;Heath M.;Jaiwal G.;Javierre C.;Labeirie J.;Monier M.;Morales U.;Mrabti A.;Mthombeni B.;Okan B.;Smith L.;Sheller J.;Sopena S.;Pellan V.;Benbernou F.;Bengrait N.;Lamoureux M.;Kralova K.;Scemama M.;Bejuit R.;Coulange A.;Berthou C.;Repincay J.;Lorenzato C.;Etienne A.;Gouet V.;Normand M.;Ourliac A.;Rondel C.;Adamo A.;Beltran P.;Barraud P.;Dubois-Gache H.;Halle B.;Metwally L.;Mourgues M.;Sotty M.;Vincendet M.;Cotruta R.;Chengyue Z.;Fournie-Lloret D.;Morrello C.;Perthuis A.;Picault P.;Zobouyan I.;Colhoun H. M.;Dempsey M. A.;McClanahan M. A.
2019
Abstract
Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4–1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20–2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25–2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78–2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65–2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, −0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89–1·11). HRs were 0·97 (95% CI 0·87–1·09) for patients with prediabetes and 1·30 (95% CI 0·93–1·81) for those with normoglycaemia (pinteraction=0·11). Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65–1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes.
Ray, K., Colhoun, H., Szarek, M., Baccara-Dinet, M., Bhatt, D., Bittner, V., et al. (2019). Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. THE LANCET DIABETES & ENDOCRINOLOGY, 7(8), 618-628 [10.1016/S2213-8587(19)30158-5].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/372769
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 598/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
