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SUMMARY After clinical trials had overwhelmingly demonstrated that treatment with thrombolytics and aspirin reduce mortality in acute myocardial infarction (AMI), the use of these agents in AMI, in particular thrombolytics, was lower than expected. This issue is reviewed with special emphasis on a series of studies undertaken by the European Secondary Prevention Study Group that was formed by researchers from 11 countries. The objective was to understand the fundamentals of the limited uptake and analyse the consequences for the overall benefit in clinical practice. It was found that 36% of the AMI patients received thrombolytics, and that the calculated maximum rate was 55%, showing that about 1/5 of the patients despite no contraindications did not receive the treatment. Altogether 72% of the patients received aspirin. Thus, failure of the physicians to act on the evidence from clinical trials was not the main factor for the low use of thrombolytics; the major reasons were ECG findings not being indications for thrombolysis and late admission in hospital after onset of symptoms. In the Norwegian cohort it was found that the patients receiving neither thrombolytics nor aspirin was a particular high-risk group with high mortality, contributing substantially to overall mortality. The total mortality was 18.1% and thus far higher than mortality reported in clinical trials. It was estimated what the mortality would have been had neither aspirin nor thrombolytics been given. The calculated mortality was 20.6%, implying an overall mortality reduction of 12% for the whole AMI cohort. Thus, the effects observed in clinical trials can not be translated into epidemiologically documented reduction in mortality, as optimal conditions for treatment with thrombolytics and aspirin are found only in a proportion of the patient groups constituting an unselected AMI population. NORSK SAMMENDRAG I kliniske forsok er det vist at behandling med trombolytika og acetylsalicylsyre gir betydelig reduksjon av mortaliteten ved akutt hjerteinfarkt. I arene etter at dette ble fastslatt var bruken av trombolytika lavere enn forventet. Dette temaet droftes med utgangspunkt i en serie studier som ble gjennomfort av European Secondary Prevention Study Group som ble dannet av forskere fra 11 land. Ett av malene var a fa kunnskap om arsakene til den begrensede bruken og analysere konsekvensene for samlet mortalitetsgevist av trombolytika og acetylsalicylsyre ved akutt hjerteinfarkt. Det ble funnet at 36% av hjerteinfarktpasientene fikk trombolytisk behandling og deretter estimert at den maksimale andelen som var kandidater for slik behandling var 55%, noe som innebaerer at 1/5 av pasientene ikke fikk behandlingen til tross for at det ikke forela kontraindikasjoner. Hovedgrunnene til den begrensede bruken av trombolytika var at en hoy andel enten manglet EKG-forandringer som kreves for slik behandling, eller at det hadde gatt lang tid fra symptomdebut til ankomst i sykehus. Manglende evne til a implementere ny kunnskap i klinisk praksis var saledes ikke en vesentlig arsak til den relativt lave bruken. Andelen som fikk acetylsalicylsyre var 72%. Spesiell analyse av den norske kohorten viste at pasientene som fikk verken trombolytika eller acetylsalicylsyre utgjorde en spesiell hoyrisikogruppe med hoy mortalitet, og som dermed bidro betydelig til den totale dodeligheten ved akutt hjerteinfarkt. Total mortalitet var 18,1% og dermed klart hoyere enn det som er funnet i kliniske studier. Det ble beregnet hva mortaliteten ville ha vaert dersom trombolytika og acetyl salicylsyre ikke hadde vaert brukt. Den beregnede mortalitet var da 20,6%, noe som innebaerer at samlet mortalitet var redusert med 12% for hele infarktgruppen. Saledes vil den gevinst som pavises i kliniske studier ikke gjenspeiles i epidemiologisk dokumentert reduksjon i mortalitet fordi de optimale betingelsene for behandling med trombolytika og acetylsalicylsyre bare er til stede hos en viss andel av pasientene som utgjor den samlede gruppen av infarktpasienter.

norsk epidemiologi

Thrombolytics and aspirin in the treatment of acute myocardial infarction: towards an understanding of factors limiting their use and consequences for overall benefit