Oral anticoagulation and risk of death: a medical record linkage study

doi:10.1136/bmj.325.7372.1073

BMJ 2002;325:1073-1075 ( 9 November )

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Oral anticoagulation and risk of death: a medical record linkage study

Anders Odén, consulting statistician, ^a Martin Fahlén, associate professor of medicine. ^b

^a Valler 190, S-442 92 Romelanda, Sweden, ^b Department of Medicine, Hospital of Kungälv, Sweden

Correspondence to: A Odén anders.oden{at}mbox301.swipnet.se

Objective: To study how mortality varies with differentdegrees of anticoagulation reflected by the international normalisedratio(INR).
Design: Record linkage analysis with death hazardestimated as a continuous function ofINR.
Data sources: 46 anticoagulation clinics in Sweden withcomputerised medicalrecords.
Subjects: Records for 42 451 patients, 3533 deaths,and 1.25 million INRmeasurements.
Main outcome measures: Mortality from all causes and from intracranialhaemorrhage.
Results: Mortality from all causes of death was stronglyrelated to level of INR. Minimum risk of death was attained at2.2 INR for all patients and 2.3 INR for patients with mechanicalheart valve prostheses. A high INR was associated with an excessmortality: with an increase of 1 unit of INR above 2.5, the risksof death from cerebral bleeding (149 deaths) and from any causewere about doubled. Among patients with an INR of $>=$ 3.0, 1069 deathsoccurred within 7 weeks; if the risk coincided with that withan INR of 2.9, the expected number of deaths would have been 569.Thus at least 500 deaths were associated with a high INR value,but not necessarily caused by thetreatment.
Conclusions: The excess mortality associated with highINR values supports the use of less intensive treatment and asmall therapeutic window, with INR close to 2.2-2.3 irrespectiveof the indication for anticoagulant treatment. More preventiveactions should be taken to avoid episodes of highINR.

What is already known on this topic
The optimal degree of anticoagulation (expressed as the international normalised ratio (INR)) for different indications is still unclear, but the increased risk of death due to bleeding at high INR values is well known

What this study adds
This large study of medical records from anticoagulation clinics in Sweden confirmed the substantial excess mortality at high INR values and indicated optimal treatment to be in a small therapeutic window with INR close to 2.2-2.3, irrespective of the indication for anticoagulant treatment

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