natgillin/translations-raw huggingface dataset:
Indehaveren af markedsføringstilladelsen er blevet anmodet om at fremlægge et fagligt begrundet forslag til en fælles tekst for hele EU, da der er forskelle mellem de nationale godkendelser med hensyn til anvendelsen af Pravachol ved:
The MAH was requested to propose and scientifically justify a common EU wide approach as there were divergences between national approvals regarding the use of Pravachol in:
Primær og blandet hyperkolesterolæmi.
Isolated or mixed hypercholesterolaemia.
Denne indikation er godkendt i alle EU' s medlemsstater, Island og Norge.
This indication was approved in all EU Member States, Iceland and Norway.
Formuleringen (og dermed den nøjagtige betydning) af den godkendte indikation er imidlertid meget forskellig i de forskellige nationalt godkendt produktresuméer.
However the wording (and therefore the precise meaning) of the approved indication is very different in the different nationally approved summaries of product characteristics.
Primær forebyggelse ved koronar hjertesygdom.
Primary prevention in Coronary Heart Disease.
Denne indikation er kun godkendt som indikation i nogle af medlemsstaterne, mens oplysningerne i andre kun er beskrevet under afsnit 5. 1 Farmakodynamiske egenskaber.
This indication was approved as an indication only in some Member States and in others the data are described only under section 5.1 Pharmacodynamic properties.
Sekundær forebyggelse ved koronar hjertesygdom.
Secondary prevention in Coronary Heart Disease.
Denne indikation er godkendt i alle medlemsstater, Island og Norge.
This indication was approved in all Member States, Iceland and Norway.
Formuleringen (og dermed den nøjagtige betydning) af den godkendte indikation er imidlertid forskellig i de forskellige medlemsstater.
However, the wording (and therefore the precise meaning) of the indication was different from member state to member state.
Desuden gælder, at under indikationen koronar hjertesygdom er indikationen “ reduktion af progression af koronararteriesklerose og reduktion af kardiale hændelser ” kun i nogle medlemsstater godkendt som særskilte indikationer.
Furthermore, within the Coronary Heart Disease indication “ slowing of the progression of coronary artery sclerosis and reduction of the incidence of cardiac events” were approved as separate indications only in some Member States.
Endelig er indikationen behandling af hyperlipidæmi efter helorgantransplantation kun godkendt i nogle medlemsstater.
Finally, only some Member States approved an indication in the treatment of hyperlipidaemia following solid organ transplant.
Denne indikation er i nogle medlemsstater begrænset til behandling efter hjerte - og nyretransplantation, i andre til behandling efter hjertetransplantation.
This indication was restricted to a treatment following cardiac and renal transplantation in some of these Member States and in some others restricted to a treatment following a cardiac transplant.
Primær hyperkolesterolæmi og blandet dyslipidæmi
Primary hypercholesterolaemia and mixed dyslipidaemia
Pravastatin er en kompetitiv hæmmer af 3- hydroxy- 3- methylglutaryl- coenzym A (HMG- CoA) reduktase, som er det enzym, der katalyserer det tidlige hastighedsbegrænsende trin i kolesterolbiosyntesen, og som afstedkommer den lipidsænkende virkning på to måder.
Pravastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme catalysing the early rate-limiting step in cholesterol biosynthesis, and produces its lipid- lowering effect in two ways.
For det første bevirker det en moderat reduktion i syntesen af intracellulært kolesterol ved reversibel og specifik kompetitiv hæmning af HMG- CoA reduktase.
First, with the reversible and specific competitive inhibition of HMG-CoA reductase, it induces a modest reduction in the synthesis of intracellular cholesterol.
Dette medfører et øget antal af LDL- receptorer på celleoverfladerne og øget receptor- medieret katabolisme og clearance af cirkulerende LDL- kolesterol.
This results in an increase in the number of LDL-receptors on cell surfaces and enhanced receptor-mediated catabolism and clearance of circulating LDL-cholesterol.
For det andet hæmmer pravastatin produktionen af low- density lipoprotein (LDL) ved at hæmme den hepatiske syntese af very low- density lipoprotein (VLDL) - kolesterol, der er precursor til LDL - kolesterol.
Secondly, pravastatin inhibits the low-density lipoproteins (LDL) production by inhibiting the hepatic synthesis of very low-density lipoproteins (VLDL) cholesterol, the LDL-cholesterol precursor.
CPMP/ 6214/ 03
CPMP/ 6214/ 03 Primary prevention of coronary heart disease
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Denne indikation er baseret på resultaterne af én undersøgelse, WOSCOPS (the West of Scotland Coronary Prevention Study).
This indication is based on the results of one outcome study, WOSCOPS (the West of Scotland Coronary Prevention Study).
” West of Scotland Coronary Prevention Study (WOSCOPS) ” var en randomiseret, dobbeltblind, placebo- kontrolleret undersøgelse med 6 595 mandlige patienter i aldersgruppen 45- 64 år med moderat til svær hyperkolesterolæmi (LDL- C:
The "West of Scotland Coronary Prevention Study (WOSCOPS)" was a randomised, double-blind, placebo-controlled trial among 6,595 male patients aged from 45 to 64 years with moderate to severe hypercholesterolaemia (LDL-C:
155- 232 mg/ dl [4, 0- 6, 0 mmol/ l]) og uden anamnetisk myokardieinfarkt, gennemsnitligt behandlet i 4, 8 år med enten 40 mg pravastatin dagligt eller placebo som tillæg til diæt.
155-232 mg/ dl [4.0-6.0 mmol/ l]) and with no history of myocardial infarction, treated for an average duration of 4.8 years with either a 40 mg daily dose of pravastatin or placebo as an adjunct to diet.
Hos pravastatin- behandlede patienter viste resultaterne:
In pravastatin-treated patients, results showed:
- nedsat risiko for død pga. koronar sygdom og for ikke- dødeligt myokardieinfarkt (relativ
- a decrease in the risk of mortality from coronary disease and of non-lethal myocardial infarction
Virkningen på disse kumulative kardiovaskulære hændelsesrater var tydelig allerede efter 6 måneders behandling,
(relative risk reduction RRR was 31%; p = 0.0001 with an absolute risk of 7.9% in the placebo group, and 5.5% in pravastatin treated patients); the effects on these cumulative cardiovascular events rates being evident as early as 6 months of treatment;
- reduktion af samlet antal dødsfald pga. kardiovaskulære hændelser (RRR 32%; p = 0, 03),
- a decrease in the total number of deaths from a cardiovascular event (RRR 32%; p = 0.03)
- når risikofaktorerne blev taget i betragtning, kunne der desuden iagttages en RRR på 24% (p =
- when risk factors were taken into account, a RRR of 24% (p = 0.039) in total mortality was also
0, 039) i total mortalitet hos patienter behandlet med pravastatin,
observed among patients treated with pravastatin;
- reduktion af den relative risiko for at skulle gennemgå myokardial revaskularisering (koronararterie -
- a decrease in the relative risk for undergoing myocardial revascularisation procedures (coronary
bypass- transplantat eller koronar angioplastik) med 37% (p = 0, 009) og koronar angiografi med 31% (p = 0, 007).
artery bypass graft surgery or coronary angioplasty) by 37% (p = 0.009) and coronary angiography by 31% (p = 0.007).
Hos patienter > 65 år kender man ikke behandlingens gavnlige virkning i henhold til ovennævnte kriterier, da disse patienter ikke indgik i undersøgelsen.
The benefit of the treatment on the criteria indicated above is not known in patients over the age of 65 years, who were not included in the study.
I denne undersøgelse fandtes ingen gavnlig virkning af pravastatin hos patienter med hyperkolesterolæmi og triglycerider > 6 mmol/ l (5, 3 g/ l) efter diæt i 8 uger.
In this study, the benefit of pravastatin treatment was not established in patients with hypercholesterolaemia associated with a triglyceride level of more than 6 mmol/ L (5.3 g/ L) after a diet for 8 weeks.
1990- 1992.
Reservations have been expressed about the extrapolation of such findings for all patients with hypercholesterolaemia; because of the age-adjusted mortality among Scottish men aged 45 to 74 years at the time WOSCOPS was conducted, i. e., 1990-1992.
100 000 i Belgien.
The mortality was highest in Europe with 886 cases per 100 000 compared with 330 cases per 100 000 in France and 542 cases per 100 000 in Belgium.
Ved at anvende Belgien som case- undersøgelse med henblik på risikoanalysekunne det påvises, at skønt populationen af skotske mænd i WOSCOPS var udvalgt af en population med højere risiko for kardiovaskulær sygdom, adskilte de sig med hensyn til observeret risiko ikke så stærkt fra andre lande som f. eks Belgien, når udvælgelseskriterierne fra undersøgelsen anvendtes.
Using Belgium as a case study for a risk analysis, it was shown that the WOSCOPS Scottish men population, although selected from a population with a higher risk of cardiovascular disease, was not so different in observed risk than in other countries, such as Belgium, when using the selection criteria of the study.
På grundlag af disse samlede resultater konkluderedes det, at resultaterne af WOSCOPS, der var iagttaget hos skotske mænd, kunne ekstrapoleres til mænd i andre europæiske lande.
Based on these overall findings, It was concluded that the WOSCOPS findings observed in Scottish men could be extrapolated to men of other European countries.
At generalisere resultaterne til kvinder var mere problematisk, da man i den belgiske case- undersøgelse ikke undersøgte, om den i WOSCOPS- undersøgelsen fundne relative risikoreduktion kunne anvendes på andre befolkningsgrupper, således kvinder.
The generalisation of these results to women was more problematic as the Belgium case report study did not investigate the applicability of the relative risk reduction observed in the WOSCOPS study to other populations such as women.
Dog indgik der både mænd og kvinder i CARE (Cholesterol and Recurrent Events) og LIPID (Long- Term Intervention with Pravastatin in Ischemic Disease) undersøgelserne.
However, CARE (Cholesterol and Recurrent Events) and LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) studies also included both men and women.
CPMP var enig i, at anvendelsen af pravastatin generaliseres til mænd og kvinder med høj risiko for kardiovaskulære hændelser, således patienter med familiær disposition for kardiovaskulære hændelser i en ung alder, vedvarende rygning, konstant hypertension, diabetes mellitus og lavt HDL - cholesterolniveau.
The CPMP agreed to generalise the use of pravastatin to men and women at high risk of cardiovascular events such as family history of early cardiovascular events, continued smoking, constant hypertension, diabetes mellitus, low HDL-cholesterol levels.
CPMP ønskede imidlertid ikke, at der indgik nogen omtale af “ metoder til revaskularisering af myokardiet ”, da de anvendte teknikker afhænger af klinisk praksis og ikke kan anses for “ hårde ” endepunkter i modsætning til de to andre kriterier: dødeligt og ikke- dødeligt myokardieinfarkt.
However, the CPMP did not want to include any reference to “ myocardial revascularisation procedure” as the techniques used depend on medical practice and cannot be considered as a “ hard” endpoint contrary to both other criteria: fatal and non-fatal myocardial infarction.
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Sekundær forebyggelse af koronar hjertesygdom
Secondary prevention of coronary heart disease
Denne indikation bygger på resultater af seks kontrollerede undersøgelser:
This indication is based from the results of six controlled studies:
PLAC I (Pravastatin Limitation of Atherosclerosis in the Coronary Arteries), PLAC II (Pravastatin, Lipids and Atherosclerosis in the Carotid Arteries), REGRESS (Regression Growth Evaluation Statin Study), KAPS (Kuopio Atherosclerosis Prevention Study) samt CARE og LIPID undersøgelserne.
PLAC I (Pravastatin Limitation of Atherosclerosis in the Coronary Arteries), PLAC II (Pravastatin, Lipids and Atherosclerosis in the Carotid Arteries), REGRESS (Regression Growth Evaluation Statin Study), KAPS (Kuopio Atherosclerosis Prevention Study), CARE and LIPID studies.
” Cholesterol and Recurrent Events (CARE) ” var en randomiseret, placebokontrolleret dobbeltblindundersøgelser, der i en periode af gennemsnitligt 4, 9 år sammenlignede virkningen af pravastatin (40 mg én gang dgl.) og placebo på dødeligheden af koronar hjertesygdom og ikke - dødeligt myokardieinfarkt hos 4 159 patienter i alderen 21 til 75 år med normalt totalt kolesterolniveau (baseline middel total cholesterol) < 240 mg/ dl, som i de foregående 3 til 20 måneder havde haft et myokardieinfarkt.
The "Cholesterol and Recurrent Events (CARE)" study was a randomised, double-blind, placebo- controlled study comparing, the effects of pravastatin (40 mg OD) on coronary heart disease death and nonfatal myocardial infarction for an average of 4.9 years in 4159 patients aged 21 to 75 years, with normal total cholesterol levels (baseline mean total cholesterol < 240 mg/ dl), who had experienced a myocardial infarction in the preceding 3 to 20 months.
Behandling med pravastatin reducerede signifikant:
Treatment with pravastatin significantly reduced:
- antal tilbagefald af koronare hændelser (enten død pga. koronar hjertesygdom eller ikke- dødeligt MI)
-  the rate of a recurrent coronary event (either coronary heart disease death or nonfatal MI) by 24%
med 24% (p = 0, 003, placebo 13, 3%, pravastatin 10, 4%);
(p = 0.003, placebo 13.3%, pravastatin 10.4%);
- reduktion af den relative risiko for at skulle gennemgå myokardial revaskularisering (koronararterie -
- the relative risk of undergoing revascularisation procedures (coronary artery bypass grafting or
Den relative risiko for apopleksi blev ligeledes reduceret med 32% (p = 0, 032), og for apopleksi og transitorisk iskæmisk attak (TIA) tilsammen med 27% (p = 0, 02).
percutaneous transluminal coronary angioplasty) by 27% (p < 0.001)., The relative risk of stroke was also reduced by 32% (p = 0.032), and stroke or transient ischaemic attack (TIA) combined by 27% (p = 0.02).
På grundlag af CARE- undersøgelsen blev indikationen sekundær forebyggelse udvidet med reduktion af kardiovaskulære og cerebrovaskulære hændelser hos udsatte patienter med normalt kolesterolniveau.
Based on the CARE study, the secondary prevention indication was extended to include the reduction of cardiovascular and cerebrovascular events in patients at risk with normal cholesterol levels.
” Long- Term Intervention with Pravastatin in Ischemic Disease (LIPID) ” var en randomiseret, dobbeltblind, placebokontrolleret multicenterundersøgelse, der i en periode på gennemsnitligt 5, 6 år sammenlignede virkningen af pravastatin (40 mg én gang dgl.) med placebo hos 9 014 patienter i aldersgruppen 31- 75 år med normalt til forhøjet serumkolesterol (baseline totalkolesterol = 155 til 271 mg/ dl [4, 0- 7, 0 mmol/ l], middel totalkolesterol = 219 mg/ dl [5, 66 mmol/ l]), med forskellige triglyceridværdier på op til 443 mg/ dl [5, 0 mmol/ l] og med anamnetisk myokardieinfarkt eller ustabil angina pectoris i de foregående 3 til 36 måneder.
The "Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID)" was a multi-center, randomised, double-blind, placebo-controlled study comparing the effects of pravastatin (40 mg OD) with placebo in 9014 patients aged 31 to 75 years for an average duration of 5.6 years with normal to elevated serum cholesterol levels (baseline total cholesterol = 155 to 271 mg/ dl [4.0-7.0 mmol/ l], mean total cholesterol = 219 mg/ dl [5.66 mmol/ l]) and with variable triglyceride levels of up to 443 mg/ dl [5.0 mmol/ l] and with a history of myocardial infarction or unstable angina pectoris in the preceding 3 to 36 months.
Behandling med pravastatin medførte signifikant mindskelse af den relative dødelighed af koronar hjertesygdom med 24% (p = 0, 0004, med en absolut risiko på 6, 4% i placebogruppen og 5, 3% hos pravastatinbehandlede patienter), af den relative risiko for koronare hændelser (enten koronar hjertesygdom med dødelig udgang eller ikke- dødeligt MI) med 24% (p < 0, 0001) og af den relative risiko for dødeligt eller ikke- dødeligt myokardieinfarkt med 29% (p < 0, 0001).
Treatment with pravastatin significantly reduced the relative risk of CHD death by 24% (p = 0.0004, with an absolute risk of 6.4% in the placebo group, and 5.3% in pravastatin treated patients), the relative risk of coronary events (either CHD death or nonfatal MI) by 24% (p < 0.0001) and the relative risk of fatal or nonfatal myocardial infarction by 29% (p < 0.0001).
For pravastatingruppen var resultaterne følgende:
In pravastatin-treated patients, results showed:
- den relative totale dødelighed mindskedes med 23% (p < 0, 0001) og den kardiovaskulære
- a reduction in the relative risk of total mortality by 23% (p < 0.0001) and cardiovascular mortality by
dødelighed med 25% (p < 0, 0001),
25% (p < 0.0001);
- den relative risiko for at skulle gennemgå myokardial revaskularisering (koronararterie- bypass
- a reduction in the relative risk of undergoing myocardial revascularisation procedures (coronary
transplantation eller perkutan transluminal koronar angioplastik) mindskedes 20% (p < 0, 0001),
artery bypass grafting or percutaneous transluminal coronary angioplasty) by 20% (p < 0.0001);
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I CARE- undersøgelsen resulterede behandling med pravastatin i en betydelig reduktion af tilbagefald af koronare hændelser (enten død pga. koronar hjertesygdom eller ikke- dødeligt MI) på 24% (p = 0, 003) og var forbundet med en reduktion af anvendelsen af koronar bypass- operation på 14, 1% i pravastatin- gruppen, sammenholdt med 18, 8% i placebo- gruppen (koronar bypass- operation eller angioplastik).
In the CARE study, treatment with pravastatin significantly reduced the rate of a recurrent coronary event (either coronary heart disease death or non-fatal MI) by 24% (p = 0.003) and was associated with a decrease in the rate of coronary bypass surgery by 14.1% in the pravastatin group, compared to 18.8% in the placebo group (coronary bypass surgery or angioplasty).
I LIPID- undersøgelsen kunne der iagttages en reduktion på 13% i myokardial revaskularisering (bypass eller angioplastik) i pravastatin- gruppen, sammenholdt med 15, 7% i placebogruppen.
In the LIPID study, a decrease in 13% in myocardial revascularisation (bypass or angioplasty) in the pravastatin group compared to 15.7% in the placebo group, was observed.
For primær forebyggelse kan CPMP imidlertid ikke godkende, at “ myokardial revaskularisering ” anføres i indikationsafsnittet, da virkningen af revaskularisering afhænger af klinisk praksis og bør anses for en følge af risikoen forbundet med myokardieinfarktreduktion.
However, as for primary prevention, the CPMP disagreed to mention “ myocardial revascularisation” in the indication section as the effects of revascularisation depends on medical practice and should be considered as a consequence of the myocardial infarction reduction risk.
- Apopleksi, transitorisk iskæmisk attak
- Stroke, transient ischaemic attack
En separat analyse af AIT (transitorisk apopleksi) og AVC (cerebrovaskulært attak) som sekundære kriterier blev udført af et særligt underudvalg som post hoc- analyse i CARE- undersøgelsen.
A separate analysis of AIT (transient strokes) and AVC as secondary criteria was performed by a specific Committee board as a post-hoc analysis in the CARE study.
I denne undersøgelse blev populationen ikke anset for repræsentativ for populationen med høj risiko for apopleksi (prævalens 43% af patienter med hypertension sammenholdt med 60% den udsatte population).
In this study, the population was not considered representative of a high-risk population of strokes (prevalence of 43% of patients with hypertension compared to a 60% rate in an at risk population).
I LIPID- undersøgelsen blev der desuden foretaget en analyse af apopleksier og ikke - hæmorragiske apopleksier som sekundære kriterier.
In the LIPID study, an analysis of strokes and non-haemorrhagic strokes was also performed as secondary criteria.
- Reduktion i antal hospitaliseringer
- Reduction of the number of hospitalisation
Virkningen af pravastatinbehandling på antal hospitaliseringer (både frekvens og varighed) blev undersøgt i WOSCOPS- undersøgelsen.
The effects of pravastatin treatment in the number of hospitalisation (both in frequency and duration) were studied in the WOSCOPS study.
Hvad angår virkning på hospitalsindlæggelser af alle andre årsager end kardiovaskulære adskilte Pravastatin sig ikke fra placebo.
Pravastatin treatment had no effect on hospital admissions for any non-cardiovascular category, relative to the placebo group.
For indlæggelser af kardiovaskulære årsager (1 234 eller 28% af det samlede antal) var der derimod en signifikant reduktion på 10, 8% (95% SI [4- 17, 4], p = 0, 01) i pravastatingruppen.
However, for cardiovascular causes (1,234 or 28% of the total), there was a significant 10.8% reduction in admissions (95% CI [4-17.4], p = 0.01) in the pravastatin group.
En tilsvarende analyse foretoges i LIPID- undersøgelsen (indlæggelsesdage og antal indlæggelser).
A similar analysis was performed in the LIPID study (hospital days and the number of admissions).
Da populationen hørte under sekundær forebyggelse, var der imidlertid et øget antal indlæggelser af kardiovaskulære årsager.
The mean number of hospitalisation days per 100 person-years of follow-up in the placebo group was 349 days compared to 296 days in the pravastatin group (a 15% reduction; p < 0.001).
I pravastatin- gruppen var der 12 516 færre indlæggelsesdage og 1 075 færre indlæggelser.
In fact, this was not due to shorter but more frequent admissions in the pravastatin group, as the median number of admissions (two) was the same in both groups.
Det gennemsnitlige antal indlæggelsesdage pr.
PTHL typically develops 3-6 months post- transplantation.
100 personårs opfølgning var i placebogruppen 349 dage, sammenhold med 296 dage i pravastatingrupen (en reduktion på 15%; p < 0, 001).
The incidence is particularly high in heart transplant patients (80%), who needed a transplant because of atherosclerotic heart disease in the native heart.
Faktisk skyldtes dette ikke kortere, men flere indlæggelser i pravastatingruppen, da det gennemsnitlige antal indlæggelser (to) var det samme i begge grupper.
As pravastatin has only a modest increase in its exposure in the presence of cyclosporine, it seems the right statin in the initial management of PTHL.
Helorgantransplantation
- Cardiac transplantation
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Resultaterne viste, at pravastatingruppen 12 måneder efter transplantation havde lavere middel (+ / - SD) kolesterolniveau end kontrolgruppen (193 + 36 mod 248 + 49 mg/ dl, p < 0, 001), mindre hyppig hjerteafstødelse ledsaget af hæmodynamisk kompromittering (3 mod 14 patienter, p = 0, 005), bedre overlevelse (94% mod 78%, p = 0, 025) og lavere forekomst af koronar vaskulopati i transplantatet, bedømt på angiografi og på autopsi (3 mod 10 patienter, p = 0, 049).
Results showed that 12 months after transplantation, the pravastatin group had lower mean (+/ -) SD cholesterol levels than the control group (193 + 36 versus 248 + 49 mg/ dL, p < 0.001), less frequent cardiac rejection accompagnied by haemodynamic compromise (3 versus 14 patients, p= 0.005), better survival (94% versus 78%, p=0.025) and a lower incidence of coronary vasculopathy in the transplant as determined by angiography and by autopsy (3 versus 10 patients, p=0.049).
Intrakoronar ultralydsmåling ved baseline og et år efter transplantationen viste desuden, at der i pravastatingruppen var mindre progression af den maksimale tykkelse af intima, 0, 11+ / - 0, 09 mm mod 0, 23+ / - 0, 16 mm i kontrolgruppen; p = 0, 002).
Furthermore, in a subgroup of study patients, intracoronary ultrasound measurements at baseline and one year after transplantation showed less progression in the pravastatin group in maximal intimal thickness, 0,11+/ - 0,09 mm versus 0,23+/ -0,16 mm in the control group; p=0.002).
Overlevelse var et objektivt endepunkt, og resultaterne af den intrakoronare ultrasonografi bedømtes blindt.
Survival was an objective end point and the findings on intracoronary ultrasonography were interpreted blindly.