Oral anticoagulation and risk of death: a medical record linkage study.
OBJECTIVE
To study how mortality varies with different degrees of anticoagulation reflected by the international normalised ratio (INR).


METHODS
Record linkage analysis with death hazard estimated as a continuous function of INR.


METHODS
46 anticoagulation clinics in Sweden with computerised medical records.


METHODS
Records for 42 451 patients, 3533 deaths, and 1.25 million INR measurements.


METHODS
Mortality from all causes and from intracranial haemorrhage.


RESULTS
Mortality from all causes of death was strongly related to level of INR. Minimum risk of death was attained at 2.2 INR for all patients and 2.3 INR for patients with mechanical heart valve prostheses. A high INR was associated with an excess mortality: with an increase of 1 unit of INR above 2.5, the risks of death from cerebral bleeding (149 deaths) and from any cause were about doubled. Among patients with an INR of > or =3.0, 1069 deaths occurred within 7 weeks; if the risk coincided with that with an 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 the treatment.


CONCLUSIONS
The excess mortality associated with high INR values supports the use of less intensive treatment and a small therapeutic window, with INR close to 2.2-2.3 irrespective of the indication for anticoagulant treatment. More preventive actions should be taken to avoid episodes of high INR.
Odén
Anders
A
Valler 190, S-442 92 Romelanda, Sweden. anders.oden@mbox301.swipnet.se
Fahlén
Martin
M
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D002423:Cause of Death; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000401:mortality; D003645:Death, Sudden / Q000209:etiology*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D016012:Poisson Distribution; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
D000925:Anticoagulants