RANDOMIZED TRIAL OF CHOLESTEROL-LOWERING IN 4444 PATIENTS WITH CORONARY-HEART-DISEASE - THE SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY (4S)

Authors
PEDERSEN TR KJEKSHUS J BERG K HAGHFELT T FAERGEMAN O THORGEIRSSON G PYORALA K MIETTINEN T WILHELMSEN L OLSSON AG WEDEL H KRISTIANSON K THOMSEN H NORDERO E THOMSEN B LYNGBORG K ANDERSEN GS NIELSEN F TALLERUPHUUS U MCNAIR A EGSTRUP K SIMONSEN EH SIMONSEN I VEJBYCHRISTENSEN H SOMMER L EIDNER PO KLARHOLT E HENRIKSEN A MELLEMGAARD K LAUNBJERG J FREUERGAARD P NIELSEN L MADSEN EB IBSEN H ANDERSEN U ENEMARK H HAARBO J MARTINSEN B DAHLSTROM CG THYRRING L THOMASSEN K JENSEN G RASMUSSEN SL SKOV N HANSEN KN LARSEN ML HAASTRUP B HJAERE I THUROE A LETH A MUNCH M WORCK R NIELSEN B THORN AG PEDERSENBJERGAARD O FOURNAISE B SIGURD B ENK B NIELSEN H JACOBSEN L SVENDSEN TL HOEGHOLM A MUNTER H KAUFMANN P HAUNSO S GRANDE P ERIKSEN C NIELSEN HH JURLANDER B PINBORG T PINDBORG J TOST H CHRISTIANSEN BD OPPENHAGEN M EGEDE F HVIDT S KJAERBY T LEMMING L KLAUSEN I MIETTINEN TA VANHANEN H STRANDBERG TE HOLTTA K LUOMANMAKI H PEKURI T VUORINEN A PASTERNACK A OKSA H SIITONEN L RIMPI R KESANIEMI YA LILJA M KORHONEN T RANTALA A RANTALA M SAVOLAINEN M UKKOLA O LAINE L VIRKKALA L LEHTO S MIETTINEN H SALOKANNEL A RAISANEN R HOGNASON J KRISTJANSDOTTIR H THORVALDSDOTTIR G SIGURDSSON G SVERRISSON JT HANSTEEN V KJELSBERG F BERGET K PETTERSEN R BALTO ER HOLM T GUNDERSEN T ASLAKSEN B ANDERSEN EH TORSVIK H FABER A INDREBO T OSE A ROTERUD T HOLSTLARSEN L WAAGE K HOLSTLARSEN E HAEREM JW AUKRUST P TORP R RISBERG K MAUSETH K GERDTS E NYGARD O HALLARAKER A GRADEK G VANGEN EM SCHARTUMHANSEN H REFSUM AM LISTERUD S GUNDERSRUD B STENE AM KLYKKEN B AAKERVIK O LORAAS A FOSS PO HAGA A THORESEN L DRIVENES A LEM P GABRIELSEN F HESTAD S RODE R HAUG BK SKJELVAN G ELDORSEN E YTREARNE K RASMUSSEN K MYHRE ESP NERMOEN I CHRISTIANSEN L KARLSEN AS WALBERG K TJONNDAL HA KULSENG B ROKSETH R NERGARD TV ROE MO TENSTAD O LOFSNES IL BERGSRUD U MELBERG TH VONBRANDIS C BARVIK S WOIE L ABRAHAMSEN AM AARSLAND T SVANES H NOER G NORDLIE KE HANEDALEN AE JOHANSEN T LARSEN CB OSTHOLM E OVERSKEID K SANDVEI P JOHANSEN A SOGNEN E AARSKOG D DALE A HEGRESTAD S REIKVAM A HAWKES L HOFF S TORJUSSEN T NORVIK R JORGENSEN C HJERMANN I LEREN P NARVESTAD A FAUSA D GJESTVANG FT NORDLAND B BRUNMARK P BIOKLUND H BIOKLUND B FORSBERG H BERGSTROM B LAAKSONEN I VESTERMARK MB MASCHER G HAMMARSTROM E TROSELL K KARLSSON L HALLSTROM L STJERNA A SLETTE MK DIDERHOLM E PBERGLUND K LINDE B AHLMARK G SAETRE H AHLBERG G SUNDKVIST K GUSTAFSSON PE GUSTAFSSON E NORRBY A JAUP B SVENSSON L WIKLUND O LINDEN T BERGH CH JONSTEG K BONNIER B LUNDIN Y ROMANUS K ULVENSTAM G JOHANSSON S WALLIN I DUDAS K ANDREASSON M TORELUND G SKARFORS E RUTER G AKESSON L WAGNER F LJUNGDAHL L WAGNER V RASMANIS G EDHAG O VOURISALO D HJELMSELL H WESLEY G LUNDKVIST L ANGMAN K OLSSON A SVENSON O KUYLENSTIERNA J FRISENETTEFICH K BERGMAN E STROMBLAD H JENSEN S JONSSON E LEVIN C ODEBERG H BENGTSSON PO HOLMESSON E HEDSTRAND H BOJO L OBERG S LEKSELL H WERNER P PERSSON S SIMONSSON M WIRENSTAM UB MOBERG B EKSTRAND AB NICOL P MALMROS B SAAW J ARCINI N KOBOSKO J ANEVIK IG GYLAND F LUNDH B WENNERHOLM M OLSSON C KJELLBERG J FABIANSON K FRASER T BERGKVIST I BERGDAHL B FLUUR C WAJERSTAM S SVENSSON KA EKHOLM L TOREBO E RYBERG A FRISELL JE HEDMAN A WALLRUP L ANDERSEN G SANDSTROM M ALBERG K FAGHER B THULIN T SVENSTAM I BJURMAN A SKOGLUND E DAHL G KJELLSTROM T JUHLIN P SJOOBOQUIST M SJOGREN A LOOGNA E JANSSON T FRIDEN J NILSSON O ANDERSSON PO HENRIKSSON C ELLSTROM J BRODERSSON H LUNDQUIST L ASLUND M BOMAN K JANSSON JH NORRFORS B HOGLUND C LUNDBLAD M LILJEFORS I WENNERSTROM L PERZ I LEIJD B FALKENBERG C BERGSTEN L STROM S ENGSTROM AC EJDEBACK J MALMBERG K HOGSTROM S STAHL L MOLLER BH LYCKSELL M SODERSTROM M HANSSON E HALLEN C STAKEBARG H BORRETZEN J HEDEN B ANDERSSON K JOHNSON O BIRGANDER LS ELANDER B LIDELL C ANDERSSON PE MARKLUND E DAHLEN M RUCKER F LOFQVIST M WANNBERG B LIM BH LARSSON O ANDERSSON G HANSSON A UCHTO M GOWENIUS M UGGELDAHL I URSING D HAMMARLUND P NYMAN P TSUPPUKA E MALMBERG L GORANSSON K HASSELGREN P INSBERG CM PETTERSON S AHRLIN A LOVHEIM O ANDERSSON LO GRUNDSTROM I
Citation
Tr. Pedersen et al., RANDOMIZED TRIAL OF CHOLESTEROL-LOWERING IN 4444 PATIENTS WITH CORONARY-HEART-DISEASE - THE SCANDINAVIAN SIMVASTATIN SURVIVAL STUDY (4S), Lancet, 344(8934), 1994, pp. 1383-1389
Citations number
36
Categorie Soggetti
Medicine, General & Internal
Journal title
Lancet → ACNP
ISSN journal
01406736
Volume
344
Issue
8934
Year of publication
1994
Pages
1383 - 1389
Database
ISI
SICI code
0140-6736(1994)344:8934<1383:RTOCI4>2.0.ZU;2-P
Abstract
Drug therapy for hypercholesterolaemia has remained controversial main ly because of insufficient clinical trial evidence for improved surviv al. The present trial was designed to evaluate the effect of cholester ol lowering with simvastatin on mortality and morbidity in patients wi th coronary heart disease (CHD). 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L o n a lipid-lowering diet were randomised to double-blind treatment with simvastatin or placebo. Over the 54 years median follow-up period, si mvastatin produced mean changes in total cholesterol, low-density-lipo protein cholesterol, and high-density-lipoprotein cholesterol of -25%, -35%, and +80%, respectively, with few adverse effects. 256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvast atin group. The relative risk of death in the simvastatin group was 0. 70 (95% CI 0.58-0.85, p=0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respective ly. There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while nonca rdiovascular causes accounted for 49 and 46 deaths, respectively. 622 patients (28%) in the placebo group and 431 (19%) in the simvastatin g roup had one or more major coronary events. The relative risk was 0.66 (95% CI 0.59-0.75, p<0.00001), and the respective probabilities of es caping such events were 70.5% and 79.6%. This risk was also significan tly reduced in subgroups consisting of women and patients of both sexe s aged 60 or more. Other benefits of treatment included a 37% reductio n (p<0.00001) in the risk of undergoing myocardial revascularisation p rocedures. This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients,