Duration of anticoagulation for venous thromboembolism
BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2758 (Published 24 May 2011) Cite this as: BMJ 2011;342:d2758
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In the article "Duration of anticoagulation for venous
thromboembolism" published on 11th June 2011 Professor Middeldorp quotes
from a meta-analysis of 33 trials that the case fatality rate of major
bleeding was 13.4%. This is a worryingly high figure but is in fact a
subset (37) of the total (276) patients who developed major bleeding out
of a total of 4374 patient years. Major bleeding was defined in 21 of the
33 trials as being clinically overt and fulfilling at least 1 of the
following 4 criteria: hospitalisation/transfusion of at least 2
units/intracranial or retroperitoneal or involving a body cavity/ fatal.
Thus the paper quotes a bleeding fatality rate of 1.31 per 100 patient
years, which is more in keeping with general experience of warfarin use.
One other point from the meta-analysis perhaps merits fuller
emphasis: there is so called "front loading" of the bleeding risk in the
first 3 months of anticoagulation treatment. The rate of major haemorrhage
in the first 3 months was 2.06% which was fatal in a total of 0.37% of
cases. For patients who continue treatment longer than 3 months the rate
of major bleeding was 2.74 per 100 patient years with a total fatality
rate of 0.63 per 100 patient years.
Thus while there is an undeniable bleeding risk linked to both short
and longer term treatment with warfarin this needs to be weighed carefully
against the risk of recurrent venous thromboembolism in up to 30% of
patients. Long term treatment is still justified in the treatment of
selected patients.
Competing interests: No competing interests
Response to Dr Tucker
Dr Tucker perceives the statement of the 13.4% case fatality rate of
bleeding while on anticoagulant therapy as misleading. Apparently, Dr
Tucker is confusing the terms "case fatality rate" and "rate" as a measure
of incidence. Case fatality rate reflects the proportion of bleeding cases
that result in death, whereas rate reflects the number of bleeding events
per person-time.
As stated in the meta-analysis, in 10 757 patients who received
anticoagulant therapy for 4374 patient-years, a total of 276 major
bleeding episodes occurred, of which 37 were fatal; resulting in a case-
fatality rate for major bleeding of 13.4% (95%CI, 9.4% to 17.4%).(1)
Indeed, fatal bleeding occurred at a rate of 1.31 per 100 patient-years
(95%CI, 1.30 to 1.32). For patients who received anticoagulants for more
than three months--that is, those patients who might be considered for
lifelong treatment according to the ACCP guidelines (2) -the case fatality
rate of major bleeding remained high at 9.1% (2.5% to 21.7%), with a rate
of fatal bleeding of 0.63 per 100 patient-years (95%CI, 0.61 to 0.65).
The risk to die of indefinite anticoagulant needs to be balanced
against the risk of dying from recurrent venous thromboembolism (VTE) when
not treated indefinitely. Another meta-analysis showed that, after
completion of anticoagulation, the case-fatality rate of recurrent VTE was
3.6% (95% CI, 1.9% to 5.7%), with a rate of fatal recurrent VTE of 0.3 per
100 patient-years (95%CI, 0.1 to 0.4).3
The abovementioned numbers are at present the best we have to enable
us to weigh the harms and benefits of indefinite anticoagulation in
patients with unprovoked VTE.
References
(1) Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in
patients taking oral anticoagulant therapy for venous thromboembolism: a
meta-analysis. Ann Intern Med 2003; 139:893-900.
(2) Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ.
Antithrombotic therapy for venous thromboembolic disease: American College
of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th
Edition). Chest 2008; 133(6 Suppl):454S-545S.
(3) Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-
fatality rates of recurrent venous thromboembolism and major bleeding
events among patients treated for venous thromboembolism. Ann Intern Med
2010; 152(9):578-589.
Competing interests: No competing interests