The Pharmaceutical Journal
Vol 269 No 7224 p703
16 November 2002

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BMJ: abstract (more)

Use lower INR targets and smaller therapeutic range, study suggests

Keeping the international normalised ratio (INR) close to 2.2–2.3, irrespective of the indication for anticoagulation treatment, could help to reduce mortality, say Swedish researchers.

They analysed the medical records of over 42,400 patients, representing about half the anticoagulation clinics in Sweden, and found that the risk of death was lowest at an INR of 2.3 for patients with mechanical heart valve prostheses, and at an INR of 2.2 for other major indications for anticoagulation (BMJ 2002;325:1073). In addition, the risk of death from cerebral bleeding decreased with increasing INR in the range of 1–1.5 (P=0.002), but rose for INR values over 1.5 (P<0.001).

Patients who reached INR levels over 3.0 after an increase in anticoagulant dose were more likely to die than those who reached this INR level spontaneously (P=0.047). The researchers say this shows that preventive action can be taken, and that more care should be taken with treatment in order to avoid high INR values and risky elevations of doses. They conclude: "We propose the use of lower target values of INR and a smaller therapeutic window compared with what is used today. An INR of 2.2–2.3 seems to be associated with the lowest risk of death for all indications."

Robin Offord, senior clinical pharmacist at Guy's and St Thomas' Hospital, London, said that tight control and monitoring of INR, as advocated in the study, would be resource intensive and not straightforward: "Future agents such as the oral direct thrombin inhibitors may revolutionise practice here," he added.

Mr Offord noted that the study had not differentiated between the cause or effect of high INR on mortality: "High INR values are known to occur in the end-stage of numerous pathologies and therefore may reflect a more general deterioration in health rather than over-anticoagulation."

In addition, he said it had excluded high-risk patients, such as those who have had further episodes of venous thromboembolic disease while on standard range oral anticoagulation. These patients, Mr Offord said, should continue to be maintained at a higher therapeutic range, between 3.0–4.0, as recommended by current guidelines.