Cerebral Venous Thrombosis: Nothing, Heparin, or Local Thrombolysis?
To the Editor:
I really must object to the recent editorial in your journal reviewing trials in cerebral venous thrombosis (CVT).1
As someone who tries to practice evidence-based medicine whenever possible, I cannot understand how Dr Bousser can suggest that although treatment with heparin offers no statistical benefit over treatment with placebo, it should be used as the treatment of choice for all CVT. She even suggests that further placebo-controlled trials would be unethical. This is a complete nonsense! Further properly conducted, placebo-controlled trials are just what are needed to answer the questions associated with the management of CVT.
I suspect some of the difficulty with this issue comes from the fact that, as physicians, we find it very difficult to do nothing. If, for example, the trial had been comparing an established treatment with a new treatment and had produced the figures this trial produced,2 we would not even be having a debate as to whether the new treatment should be adopted. No benefit would have been shown, and unless it was superior in other ways, such as side effect profile or pricing, it would be abandoned.
With this in mind, it is difficult to conceive of a cheaper or more side-effect-free treatment than nothing.
- Copyright © 1999 by American Heart Association
Bousser M-G. Cerebral venous thrombosis: nothing, heparin or local thrombolysis. Stroke.. 1999;30:481–483.
de Bruijn SFTM, Stam J, for the Cerebral Venous Sinus Thrombosis Group. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke.. 1999;30:484–488.
I am afraid I don’t really understand what point Dr Lewis wants to make about my editorial on CVT.R1 Does he really mean that “nothing” is the treatment of choice for CVT? How many CVT patients has he treated with “nothing,” and what was the outcome? How sure is he that “it is difficult to conceive of a cheaper and more side-effect-free treatment than nothing”? Has he calculated how much it would cost if a previously healthy young person died or became disabled for life? Is he so sure that denial of a potentially effective treatment is better than side effects of treatment, particularly in the case of CVT, in which a careful review of the literature shows the excellent tolerance for heparin? Does Dr Lewis want to perform another placebo-controlled trial in CVT? If so, has he calculated the number of patients that would be required in a condition with such a diversity of clinical presentation, neuroradiological patterns, and outcomes? Has he objectively considered the results of the meta-analysis of the 2 available randomized trials, which show that with heparin there is an absolute reduction in mortality of 14% and in death or dependency of 15%, with relative risk reductions of 70% and 56%, respectively.R2 R3 I maintain that although these differences do not quite reach statistical significance (because the numbers are too small), they are highly meaningful from a clinical standpoint. Indeed, the risk reductions are of far greater magnitude than those reported for aspirin, which has been recommended in the acute treatment of arterial stroke.R4 R5
Trying to practice evidence-based medicine (as I am also doing) should not preclude the practitioner from using his or her own experience, particularly when it is in keeping with that of others and with the results of randomized trials. After 25 years of experience with more than 180 CVT patients (including 16 in the last 12 months), I still do not know how to predict which patients are going to recover spontaneously (those who could be treated with “nothing”) and which are going to extend their thrombosis or develop pulmonary embolism (those who certainly require heparin). Given this unpredictability and given together the beneficial trend observed with heparin in the 2 randomized trials, the excellent results obtained in large open series, and heparin’s good tolerance, I do not think it is “complete nonsense” to state that heparin remains at present the first-line treatment for CVT, and I maintain that it is more urgent to concentrate our efforts on early diagnosis and treatment rather than embarking on yet another randomized trial.
Bousser MG. Cerebral venous thrombosis: nothing, heparin, or local thrombolysis? Stroke.. 1999;30:481–483. Editorial.
de Bruijn SFTM, Stam J, for the Cerebral Venous Sinus Thrombosis Group. Randomised, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke.. 1999;30:484–488.