FrancophonIA/ELRC3.0 huggingface dataset:
English: It is considered that the study had co-primary endpoints and hierarchical primary and secondary endpoint analyses.
Slovenian: Šteje se, da je imela študija so-primarne opazovane dogodke ter hierarhične analize primarnega in sekundarnega opazovanega dogodka.
English: However, ignoring double blind by using no treatment as comparator (as in GISSI-P) ignores another important concept in clinical trials, i.e. the use of a (blinded) comparator in order to control the other effects than the investigational drug, and deviation of this principle should only be needed or suitable "when it is difficult or impossible to avoid" (ICH E10 guideline on Choice of control group in clinical trials).
Slovenian: Vendar pa neupoštevanje načela dvojno slepe zasnove z uporabo nezdravljenja kot primerjalnega načina zdravljenja (kot v preskušanju GISSI-P) ne upošteva drugega pomembnega koncepta pri kliničnih preskušanjih, tj. uporabe (slepega) primerjalnega zdravila za kontrolo drugih učinkov, kot jih ima preskušano zdravilo, odstopanje od tega načina pa bi moralo biti potrebno ali primerno le, „kadar se mu je težko ali nemogoče izogniti“ (smernice ICH E10 o izbiri kontrolne skupine pri kliničnih preskušanjih).
English: Similar to OMEGA trial, a lack of effect of in this indication was observed.
Slovenian: Podobno kot v preskušanju OMEGA so tudi pri tej indikaciji opazili pomanjkljiv učinek.
English: Studies in patients with an implantable cardioverter defibrillator (ICD) showed inconsistent results regarding antiarrhythmic efficacy (Leaf et al.8, 2005; Brouwer et al.9 2006, Raitt et al.10, 2005; Weisman et al.11, 2017).
Slovenian: Študije pri bolnikih z vsadnim kardioverterdefibrilatorjem so pokazale neskladne rezultate v zvezi z antiaritmično učinkovitostjo (Leaf idr.8, 2005; Brouwer idr.9, 2006, Raitt idr.10, 2005; Weisman idr.11, 2017).
English: In GISSI-P, a reduction of sudden death events was seen in secondary two-way analyses of fatal events.
Slovenian: V študiji GISSI-P so pri sekundarnih dvosmernih analizah dogodkov s smrtnim izidom opazili zmanjšanje dogodkov nenadne smrti.
English: These limitations include the open-label study design with no study medication in the control arm, the small magnitude of effect, the unusual and unexpected observation of an effect on fatal cardiovascular events only in the absence of any effect on non-fatal events and poor precision of the results.
Slovenian: Med temi omejitvami so odprta zasnova študije brez preskušanega zdravila v kontrolni skupini, majhen učinek, nenavadno in nepričakovano opažanje učinka le na srčno-žilne dogodke s smrtnim izidom v odsotnosti kakršnega koli učinka na dogodke brez smrtnega izida in nenatančnost rezultatov.
English: All these studies carry the risk of a selection bias, which is supported by baseline data provided, e.g. in the retrospective cohort study by Polle (2013)7 only 1 % of post MI patients who were screened were included in the analysis.
Slovenian: Pri vseh teh študijah obstaja tveganje za pristranskost pri izbiri, kar podpirajo predloženi izhodiščni podatki; na primer v retrospektivni kohortni študiji, ki jo je izvedel Polle (2013)7, so v analizo vključili le 1 %
English: OMEGA trial was based on a more robust and adequate design than GISSI-P.
Slovenian: Preskušanje OMEGA je temeljilo na trdnejši in ustreznejši zasnovi kot preskušanje GISSIP.
English: If there was a relevant beneficial antiarrhythmic effect of omega-3 acid ethyl esters, as has been stated, it should also have been relevant for those patient populations at increased cardiovascular risk included in these studies.
Slovenian: Če bi omega-3kislinski etilestri imeli pomemben koristen antiaritmični učinek, kot so trdili, bi morali pomemben učinek opaziti tudi pri tistih populacijah bolnikov s povečanim srčno-žilnim tveganjem, ki so bile vključene v te študije.
English: The registration of Omacor was based on the GISSI-P study, however, the results of the GISSI-P trial are considered rather weak, since the study has methodological limitations.
Slovenian: Registracija zdravila Omacor je temeljila na študiji GISSI-P; vendar se rezultati preskušanja GISSI-P štejejo za precej šibke, saj ima ta študija metodološke omejitve.
English: The opinion of the Group was split: most experts believed that the level of evidence from GISSI-P together with the results from OMEGA is not supportive for using these products in secondary prevention after MI in addition to current standard of care.
Slovenian: Mnenje skupine je bilo deljeno: večina strokovnjakov je menila, da raven dokazov iz preskušanja GISSI-P v kombinaciji z rezultati preskušanja OMEGA ne podpira uporabe teh zdravil v sekundarni preventivi po miokardnem infarktu poleg veljavnega standarda oskrbe.
English: The OMEGA study included close to 2000 patients in both arms and over 300 MACE events were reported, more in the omega-3 group than in the placebo group OR 1.25 (0.96-1.52).
Slovenian: V študijo OMEGA je bilo v obeh skupinah vključenih skoraj 2 000 bolnikov, v njej pa so poročali o več kot 300 dogodkih MACE, več v skupini z omega-3 kot v skupini s placebom (razmerje obetov 1,25; 0,96-1,52).
English: With respect to the high risk group of known intolerance to one or more guideline recommended cardiovascular medications, there is no data available supporting better adherence to omega-3 acid ethyl esters compared to other pharmacological interventions and evidence for efficacy of Omacor in this specific population is lacking.
Slovenian: Kar zadeva visokorizično skupino z znano intoleranco na eno ali več zdravil za zdravljenje srčno-žilnih bolezni, ki so priporočena po smernicah, ni razpoložljivih podatkov, ki bi podpirali boljšo komplianco pri jemanju omega-3-kislinskih etilestrov v primerjavi z drugimi farmakološkimi intervencijami, poleg tega pa manjkajo dokazi o učinkovitosti zdravila Omacor pri tej specifični populaciji.
English: In addition, it may be questioned if the results are relevant in the context of current MI standard of care which has substantially evolved since the time the study was performed and secondary prevention of CVD.
Slovenian: Poleg tega bi lahko bilo vprašljivo, ali so rezultati ustrezni z vidika zdajšnje standardne oskrbe pri miokardnem infarktu, ki je od takrat, ko je bila izvedena študija, bistveno napredovala, in z vidika sekundarne preventive srčno-žilnih bolezni.
English: The OMEGA trial was conducted in patients with the approved indication, i.e. MI and used the approved dose of Omacor (1 g/day).
Slovenian: Preskušanje OMEGA je bilo izvedeno pri bolnikih z odobreno indikacijo, tj. miokardnim infarktom, in z uporabo odobrenega odmerka zdravila Omacor (1 g/dan).
English: • It has been hypothesised that the results of the GISSI-P trial was driven by a reduced risk of sudden death, potentially based on an antiarrhythmic effect of omega-3.
Slovenian: • Domnevalo se je, da so bili rezultati preskušanja GISSI-P predvsem posledica zmanjšanega tveganja za nenadno smrt, ki bi lahko temeljilo na antiaritmičnem učinku omega-3-maščobnih kislin.
English: Moreover, the American Heart Association states that use of omega-3 fatty acid supplements is ‘reasonable' for patients with prevalent coronary heart disease such as MI, indication that strength of recommendation is therefore low (Class IIa/IIb Recommendation).
Slovenian: Poleg tega ameriško združenje za srce navaja, da je uporaba dopolnil z omega-3maščobnimi kislinami pri bolnikih z razširjeno koronarno boleznijo srca, kot je miokardni infarkt, „smiselna“, kar pomeni, da je moč priporočila majhna (priporočilo razreda IIa/IIb).
English: Therefore omega-3 fatty acids are also termed n-3 polyunsaturated fatty acids (n-3 PUFA).
Slovenian: Zato omega-3-maščobnim kislinam pravimo tudi n-3 večkrat nenasičene maščobne kisline (n-3 PUFA).
English: Considering that the high-risk groups of patients with type 2 diabetes, patients with no acute PCI after MI, and patients with impaired systolic function (EF < 50%) have been identified based on post-hoc subgroup analyses conducted on GISSI-P and that these specific groups are not treated according to the current standard of care, the results of these subgroups are not representative and therefore do not support the proposed indication.
Slovenian: Glede na to, da so bili s post hoc analizami podskupin v preskušanju GISSI-P kot skupine bolnikov z velikim tveganjem prepoznani bolniki s sladkorno boleznijo tipa 2, bolniki brez takojšnjega perkutanega koronarnega posega po miokardnem infarktu in bolniki z oslabljeno sistolično funkcijo (EF < 50 %) ter da teh specifičnih skupin ne zdravijo v skladu z veljavnim standardom oskrbe, rezultati pri teh podskupinah niso reprezentativni in zato ne podpirajo predlagane indikacije.
English: Even though the incidence of sudden death may have been too low to draw firm conclusions, the OR was 1.25 (0.90-1.72) for total mortality and 1.21 for MACE (0.96 - 1.52), so it is considered unlikely that a beneficial effect could have been shown with a larger trial.
Slovenian: Čeprav je bila incidenca nenadne smrti morda premajhna, da bi lahko podali trdne zaključke, je razmerje obetov znašalo 1,25 (0,90-1,72) za celokupno umrljivost in 1,21 za MACE (0,96-1,52), zato ni verjetno, da bi bilo v obsežnejšem preskušanju mogoče dokazati koristen učinek.
English: • As a consequence, the CHMP considered that the indication “Secondary prevention after myocardial infarction” at the dose of 1 g/day should be deleted with additional consequential changes in the product information.
Slovenian: • Posledično je menil, da je treba indikacijo „sekundarna preventiva po miokardnem infarktu“ v odmerku 1 g/dan izbrisati iz informacij o zdravilu, skupaj z dodatnimi spremembami, ki so potrebne zaradi tega.
English: They also inhibit very-low-density lipoprotein (VLDL) synthesis in the liver, which reduces triglyceride concentrations.
Slovenian: Poleg tega zavirajo sintezo lipoproteina zelo majhne gostote v jetrih, kar zmanjša koncentracije trigliceridov.
English: CHMP also considered the grounds submitted by the MAHs as basis for their request for re-examination of the CHMP recommendation as well as the views of a second Cardiovascular Scientific Advisory group held on the 19 of March 2019.
Slovenian: Odbor CHMP je upošteval tudi razloge, ki so jih kot podlago za svojo zahtevo za ponovno proučitev priporočila odbora predložili imetniki dovoljenj za promet z zdravili, in stališča druge znanstveno-svetovalne skupine za srčno-žilna vprašanja, ki je potekala 19. marca 2019.
English: In this regard, the results of the GISSI-P trial are not in line with the current standard of care and therefore with the approved indication of Omacor “in addition to other standard therapy (e.g. statins, antiplatelet medicinal products, beta-blockers, ACE inhibitors”.
Slovenian: V tem smislu rezultati preskušanja GISSI-P niso v skladu s trenutnim standardom oskrbe in zato z odobreno indikacijo za uporabo zdravila Omacor „poleg druge standardne terapije (npr. statinov, antiagregacijskih zdravil, zaviralcev beta, zaviralcev ACE)“.
English: These were not rich enough to allow for a full adjustment of differences in risk profiles or to mirror real life post MI situations (e.g. no data regarding smoking history, BMI/obesity, physical exercise were reported in the Macchia study).
Slovenian: Ti niso bili dovolj raznovrstni, da bi omogočali popolno prilagoditev razlik v profilih tveganja ali da bi odražali dejanske primere po miokardnem infarktu (v študiji, ki jo je izvedel Macchia, na primer ni bilo nobenih podatkov o kajenju, ITM/debelosti ali telesni dejavnosti).
English: Total mortality was also numerically higher in the omega-3 fatty acids group OR 1.25 (0.90-1.72).
Slovenian: Tudi skupna smrtnost je bila številčno večja v skupini omega-3-maščobnih kislin (razmerje obetov 1,25; 0,90-1,72).
English: In addition to MI, ACS is also associated with unstable angina.
Slovenian: Razen z miokardnim infarktom je AKS povezan tudi z nestabilno angino.
English: In conclusion, the totality of data does not support the efficacy of omega-3 fatty acids in prevention after myocardial infarction, including in high-risk patients.
Slovenian: Skratka, celota podatkov ne podpira učinkovitosti omega3-maščobnih kislin pri preventivi po miokardnem infarktu, niti pri bolnikih z velikim tveganjem.
English: Therefore, at the most about 1/3 of the 11,324 randomized patients received appropriate baseline medication at any time during the first year and not more than 5% over the entire first year.
Slovenian: 11 324 randomiziranih bolnikov, celotno prvo leto pa največ 5 % bolnikov.
English: Even though the incidence of sudden death may have been too low to draw firm conclusions, the OR for MACE and total mortality was above 1.21 and 1.25 respectively with lower CI close to 1 not supporting an effect in the approved indication.
Slovenian: Čeprav je bila incidenca nenadne smrti morda premajhna, da bi omogočala trdne zaključke, je bilo razmerje obetov nad 1,21 za MACE in nad 1,25 za celokupno umrljivost, s spodnjo mejo IZ blizu 1, kar ne podpira učinka pri odobreni indikaciji.
English: The therapeutic effect of omega-3 fatty acids has been attributed to their possible involvement on eicosanoid balance, lipid metabolism, and cell membranes.
Slovenian: Terapevtski učinek omega-3-maščobnih kislin pripisujemo njihovemu možnemu vplivu na ravnovesje eikozanoidov, presnovo lipidov in celične membrane.
English: However CHMP still considered that the results of the GISSI-P trial are inconclusive, since the study has several limitations.
Slovenian: Vendar je odbor CHMP še vedno menil, da so rezultati preskušanja GISSI-P nejasni, saj ima študija več omejitev.
English: Moreover, the population included in the REDUCE-IT trial is not comparable with the population of the GISSI-P trial and the indication under review (patients with history of MI), since in addition to established cardiovascular disease or diabetes and other risk factors, patients in the REDUCE-IT trial suffered also from hypertriglyceridemia (> 60% of the patients had TG levels ≥ 200 mg/dL)
Slovenian: vključena v preskušanje REDUCE-IT, ni primerljiva s populacijo preskušanja GISSI-P in obravnavano indikacijo (bolniki z anamnezo miokardnega infarkta), saj so imeli bolniki, vključeni v preskušanje REDUCE-IT, poleg ugotovljene bolezni srca in žilja ali sladkorne bolezni ter drugih dejavnikov tveganja tudi hipertrigliceridemijo (> 60 % bolnikov je imelo ravni trigliceridov ≥ 200 mg/dl).
English: Medicinal products containing omega-3 acid ethyl esters have been approved in the majority of the European Union Member States for secondary prevention after myocardial infarction (MI) and in the treatment of hypertriglyceridaemia.
Slovenian: Zdravila, ki vsebujejo omega-3-kislinske etilestre, so v večini držav članic Evropske unije odobrena za sekundarno preventivo po miokardnem infarktu (MI) in pri zdravljenju hipertrigliceridemije.
English: As discussed above, in the last PSUSA for omega-3-acid-ethyl esters, “increase in bleeding time in patients with haemorragic diathesis or receiving treatment with anticoagulants” and “increase in hepatic enzymes that require monitoring in hepatic patients” was included as identified risks.
Slovenian: Kot je navedeno zgoraj, so v okviru zadnjega postopka PSUSA za omega-3kislinske etilestre kot ugotovljeni tveganji vključili „podaljšanje časa krvavitve pri bolnikih, ki imajo hemoragično diatezo ali se zdravijo z antikoagulansi“ in „povišanje vrednosti jetrnih encimov, ki zahteva spremljanje pri jetrnih bolnikih“.
English: Upon request from the CHMP, a SAG CVS meeting was convened on 10 October 2018.
Slovenian: Na zahtevo odbora CHMP se je 10. oktobra 2018 sestala znanstveno-svetovalna skupina za srčno-žilna vprašanja (SAG CVS).
English: • The CHMP considered that, even though it is acknowledged that the GISSI-P clinical trial was the basis for the original approval of the secondary prevention indication in the light of more recent data and information, the study is considered to have some serious limitations that cast doubts on the results.
Slovenian: • Odbor CHMP je menil, da ima klinično preskušanje GISSI-P, ki je sicer bilo podlaga za prvotno odobritev indikacije sekundarne preventive, glede na novejše podatke in informacije nekaj velikih omejitev, ki vzbujajo dvom o rezultatih.
English: Even though doses and populations in these studies do not fully represent the approved secondary prevention indication, all studies include patients with cardiovascular disease and therefore, these studies are relevant in the context of omega-3 in secondary prevention after MI.
Slovenian: Čeprav odmerki in populacije v teh študijah niso popolnoma reprezentativni za odobreno indikacijo sekundarne preventive, so bili v vse študije vključeni bolniki s srčno-žilno boleznijo, zato so te študije z vidika uporabe omega-3-maščobnih kislin pri sekundarni preventivi po miokardnem infarktu ustrezne.
English: The latter concern also applies to post-hoc analyses in patients with or without anti-platelet medicinal products, betablockers or ACE-inhibitors.
Slovenian: Slednje se nanaša tudi na post hoc analize pri bolnikih z antitrombotiki, zaviralci beta ali zaviralci ACE ali brez njih.
English: The patient representative considered there was value to having these products available and not to discourage this aspect of patients' choice given the long history of the use of fish oils in adjunctive medicine and as dietary supplements particularly as there was no evidence of harm with omega-3 supplementation.
Slovenian: Predstavnik bolnikov je menil, da je ta zdravila smiselno imeti na voljo in da naj se glede na dolgo zgodovino uporabe ribjih olj v dopolnilni medicini in v obliki prehranskih dopolnil ta del izbire bolnikov ne zavrača, še zlasti ker ni dokazov o škodljivosti dodajanja omega-3-maščobnih kislin.
English: • The Committee for Medicinal Products for Human Use (CHMP) considered the procedure under Article 31 of Directive 2001/83/EC for Omega-3 acid ethyl esters - containing medicinal products for oral in use in secondary prevention after myocardial infarction.
Slovenian: • Odbor za zdravila za uporabo v humani medicini (CHMP) je obravnaval postopek v skladu s členom 31 Direktive 2001/83/ES za zdravila, ki vsebujejo omega-3-kislinske etilestre, za peroralno uporabo pri sekundarni preventivi po miokardnem infarktu.
English: They noted that this treatment is not recommended in the current guidelines for prevention of CVD by the European Society of Cardiology and the European Atherosclerosis Society.
Slovenian: Ugotovili so, da v trenutnih smernicah za preprečevanje srčnožilnih bolezni tega zdravljenja ne priporoča niti Evropsko kardiološko združenje niti Evropsko združenje za aterosklerozo.
English: Recently published RCTs (ASCEND by Bowman et al. 201812, VITAL by Manson et al. 201913, REDUCEIT by Bhatt et al. 201914) do not provide evidence for the efficacy of omega-3 administration (1 g daily) for the indication under review.
Slovenian: Nedavno objavljena randomizirana nadzorovana preskušanja (ASCEND, Bowman idr., 201812; VITAL, Manson idr., 201913; REDUCE-IT, Bhatt idr., 201914) ne podpirajo učinkovitosti dajanja omega-3maščobnih kislin (1 g na dan) pri obravnavani indikaciji.
English: As the European guidelines do not recommend omega-3 fatty acid medicinal products, they apparently consider the level of evidence and the strength of the recommendation of omega-3 fatty acids in prevention of cardiovascular events both in patients after MI and in patients with other CV conditions rather weak.
Slovenian: Ker se po evropskih smernicah zdravila z omega-3-maščobnimi kislinami ne priporočajo, se raven dokazov in trdnost priporočila omega-3-maščobnih kislin za preprečevanje srčno-žilnih dogodkov tako pri bolnikih po miokardnem infarktu kot tudi pri bolnikih z drugimi srčno-žilnimi boleznimi očitno štejeta za dokaj neprepričljivi.
English: The MAHs proposed, as part of their grounds for re-examination, a modification of the indication for use in high-risk patients, i.e. type 2 diabetes, no acute PCI after MI, impaired systolic function (EF < 50%), known intolerance to one or more guideline recommended cardiovascular medications.
Slovenian: Imetniki dovoljenj za promet z zdravili so v predloženih razlogih za ponovni pregled predlagali spremembo indikacije za uporabo pri bolnikih z velikim tveganjem, tj. sladkorno boleznijo tipa 2, brez takojšnjega perkutanega koronarnega posega po miokardnem infarktu, z oslabljeno sistolično funkcijo (EF < 50 %) in z znano intoleranco na eno ali več po smernicah priporočenih srčno-žilnih zdravil.
English: The randomised controlled trials were considered most relevant for the evaluation of the efficacy of omega-3 fatty acids, in particular the results of the GISSI-P and OMEGA trials.
Slovenian: Kot najustreznejša za oceno učinkovitosti omega-3-maščobnih kislin so bila ocenjena randomizirana nadzorovana preskušanja, še zlasti rezultati preskušanj GISSI-P in OMEGA.
English: With respect to the GISSI-P trial, no new issues have been identified, with the exception of the statement of the MAHs that post-hoc analyses conducted on GISSI-P demonstrated that concomitant treatment with anti-platelet agents, beta-blockers, ACE inhibitors and statins did not alter the therapeutic benefit of Omacor.
Slovenian: V zvezi s preskušanjem GISSI-P niso bile ugotovljene nobene nove zadeve, razen trditve imetnikov dovoljenj za promet z zdravili, da so post hoc analize preskušanja GISSI-P pokazale, da sočasno zdravljenje z antitrombotiki, zaviralci beta, zaviralci ACE in statini ni vplivalo na terapevtske koristi zdravila Omacor.
English: The Swedish national competent authority considered that in light of recent clinical trials, the clinical benefit of omega-3 acid ethyl esters containing products in prevention after MI should be re-evaluated.
Slovenian: Švedski pristojni nacionalni organ je menil, da bi morali glede na najnovejša klinična preskušanja ponovno oceniti klinične koristi zdravil, ki vsebujejo omega-3-kislinske etilestre, pri preventivi po miokardnem infarktu.
English: The issue is highlighted by the fact that omega-3 acid ethyl esters had little effect when compared to the Vitamin E arm in the same trial.
Slovenian: Težavo osvetljuje dejstvo, da so imeli omega-3-kislinski etilestri le malo učinka v primerjavi z vitaminom E, ki ga je prejemala skupina v istem preskušanju.
English: This potential positive effect on mortality has not been reproduced in subsequent trials and the antiarrhythmic effect has not been confirmed in trials examining patients with ICD.
Slovenian: Ta morebitni pozitivni učinek na umrljivost se v poznejših preskušanjih ni ponovil, v preskušanjih, v katerih so proučevali bolnike z vsadnim kardioverter-defibrilatorjem, pa antiaritmičnega učinka niso potrdili.
English: The provided meta-analyses showed both positive and negative effects of omega-3 fatty acid treatment on the risk of cardiovascular events.
Slovenian: Predložene metaanalize so pokazale tako pozitivne kot negativne učinke zdravljenja z omega-3maščobnimi kislinami na tveganje za srčno-žilne dogodke.
English: Treatment with icosapent ethyl 4g/day was associated with an increase in hospitalization for atrial fibrillation of flutter in the REDUCE-IT trial.
Slovenian: Zdravljenje z ikozapent etilom v odmerku 4 g/dan je bilo v preskušanju REDUCE-IT povezano s povečanim številom hospitalizacij zaradi atrijske fibrilacije ali undulacije.
English: Omega-3 acid ethyl esters are an ethyl esters of long-chain polyunsaturated fatty acids with an eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) content of no less than 85% and an EPA to DHA ratio of 0.9 to 1.5.
Slovenian: Omega-3-kislinski etilestri so etilestri dolgoverižnih, večkrat nenasičenih maščobnih kislin z najmanj 85-odstotno vsebnostjo eikozapentaenojske kisline (EPA) in dokozaheksaenojske kisline (DHA) ter razmerjem med EPA in DHA 0,9 proti 1,5.
English: Studies investigating the effect of omega-3 acid ethyl esters medicinal products on atrial and ventricular arrhythmias did not demonstrate a clinically relevant antiarrhythmic efficacy.
Slovenian: Študije, v katerih so proučevali učinek zdravil, ki vsebujejo omega-3-kislinske etilestre, na atrijsko in prekatno aritmijo, niso pokazale klinično pomembne antiaritmične učinkovitosti.