Low-molecular-weight
heparins or heparinoids versus standard unfractionated heparin for acute
ischaemic stroke
P Sandercock, C Counsell, SL Stobbs
DOI: 000110.001002/14651858
David
K. Cundiff, MD
Date received: June 24, 2007
In the background of this review, it clearly states that unfractionated heparin (UFH) does not benefit people with acute ischaemic stroke: “These data do not support the routine use of any anticoagulant regimen - whether standard UFH, LMWHs, heparinoids, or oral anticoagulants - in patients with acute confirmed or presumed ischaemic stroke.” Since UFH doesn’t benefit patients with acute ischemic stroke and causes CNS bleeding, it makes no sense to do a review of RCTs which all have UFH as the control.
Despite the absence of benefit of LMWH for any of the major
clinical endpoints (death, vascular death, disability), the implications for
practice appear to justify the use of LMWH and heparinoids in some cases of acute
ischemic stroke based on the non statistically significant superiority of LMWH
and heparinoids over UFH in DVT and PE. The implications for practice should
read, “Do not use any anticoagulants in patients with acute ischemic stroke.”
Likewise, the implications for research should say, “It would be unethical to
conduct further trials of anticoagulants in patients with acute ischemic
stroke.”
The first version of the review was prepared at a time when there was uncertainty about the overall effects of heparins in acute ischaemic stroke. Since then, as the commenter states, evidence has emerged which shows that there is no net benefit from the immediate anticoagulation in this setting. However, as is often the case, this evidence did not alter the beliefs of some clinicians, and hence, heparin is still used in some countries, in certain types of patient with acute ischaemic stroke, for specific reasons and especially for prevention of venous thrombo-embolism.
This review is now based on the premise that if a clinician plans to treat a patient for some special reason with some form of heparin then the choice of agent should be evidence based. The wording of the 'Implications for practice' and 'Implications for research' sections reflect this.
I should point out that this review is currently being updated, and we have identified three further trials comparing LMWH with UFH in acute stroke, which testifies to the belief among some clinicians in the value of this form of treatment. The emergence of new evidence is a good reason to keep the review up to date.
Commenter: David K Cundiff, MD (22 June 2007)
Reply: Professor Peter Sandercock (9 July 2007)
My Rebuttal (July 21, 2008)
I thank Dr.
Sandercock for his reply.
As mentioned by
Dr. Sandercock, when this review was undertaken, the reviewers did not know
that anticoagulants provide no net benefit in acute ischaemic stroke. Now we
know that they are ineffective for this indication. Anticoagulants have
significants risks and costs. The justification for condoning their use and
encouraging more RCTs comparing different anticoagulants despite the evidence
that anticoagulants provide no net benefit for stroke patients appears at
variance with the founding principles of the Cochrane Collaboration.
As I understand
it, the premise of Cochrane Collaboration is that RCTs and other scientific
evidence should be systematically analysed to determine what does and what does
not benefit patients. Changing the premise of this review to, “if a clinician
plans to treat a patient for some special reason with some form of heparin then
the choice of agent should be evidence based” should be discussed at Cochrane
policy meetings.
“I should point out that this review is
currently being updated, and we have identified three further trials comparing
LMWH with UFH in acute stroke, which testifies to the belief among some
clinicians in the value of this form of treatment.”
The advent of
three further trials comparing LMWH with UFH in acute stroke would appear to
indicate drug company interest in expanding the indications for anticoagulants
rather than the rejection by clinicians of the evidence that these drugs don’t
work in acute stroke.
Given that the evidence has emerged that there is
no net benefit from anticoagulation for acute ischaemic stroke, the wording of
the plain language summary and the abstract conclusion should reflect this.