Immediate Anticoagulation for Acute Stroke in Atrial Fibrillation
“No benefit of heparin has been demonstrated for acute stroke patients with AF [atrial fibrillation]; whether selected subgroups would respond differently remains to be proven. Aspirin followed by early initiation of warfarin for long-term secondary prevention is reasonable antithrombotic management.”1
The quote above is the conclusion of a careful review of the randomized trial evidence that was available in 2002, yet it is clear that many physicians and neurologists still cling to the nonevidence-based habit of giving intravenous heparin for acute ischemic stroke associated with AF.2–5 While some dispute the validity of the trial evidence,5,6 there are others who accept that there is no evidence of net benefit from heparin in this setting.1,3,7 Indeed the American Stroke Association/American Academy of Neurology scientific statement on the subject concludes, “IV, unfractionated heparin or high-dose LMW heparin/heparinoids are not recommended for any specific subgroup of patients with acute ischemic stroke that is based on any presumed stroke mechanism or location (eg, cardioembolic, large vessel atherosclerotic, vertebrobasilar, or ‘progressing’ stroke) because data are insufficient (Grade U).”8
Because this high-quality practice guideline concludes there is no reliable evidence to support immediate anticoagulation, it is worth examining the determinants of current clinical practice. A survey of 36 US academic medical centers showed that 29% of a sample of 497 patients with acute ischemic stroke were treated with intravenous heparin, but the proportion-treated varied enormously between centers; from “not at all” in 7 centers to 88% in 1 center.2 A survey of opinion among 280 neurologists from the US and 270 neurologists from Canada showed, despite the publication of 4 clinical trials, which have not shown any long-term benefit from heparin for patients with acute stroke, both US and Canadian neurologists would use IV heparin in large numbers for this condition.3 US neurologists were significantly more likely than Canadian neurologists to use IV heparin. US neurologists more often cited medicolegal factors as a potential influence on the decision-making process than Canadian neurologists.3 Similarly, a survey of 180 neurologists in Michigan showed the vast majority of neurologists in Michigan would use IV heparin for patients with AF-related stroke (91% of those with a defined opinion). Medicolegal factors influenced the selection of heparin as a therapy for 41% of physicians. In summary, it appears the medicolegal system in US has a very powerful effect that tends to retain this nonevidence-based treatment!
The situation in Germany is similar in that there is frequent but variable use of IV heparin; full anticoagulation with heparin (“full dose”) was performed on selected patients in 32/33 stroke units (97%). The selection criteria and thus the frequency of high-dose heparin use varied widely among the different centers.5 The variation was attributed to “individualisation of the therapy in every case”; ie, the selection criteria were based on physiological principles rather than evidence from randomized trials.5 In the UK, IV heparin was hardly used at all in acute ischemic stroke of any type.9
Such enormous variations in clinical practice are hard to justify. Variation between countries and between centers within the same country in the use of a particular treatment often indicates that there is no reliable evidence on which to base treatment decisions. This certainly appears true for this particular controversy. Unfortunately, I suspect there are not enough clinicians with sufficient equipoise who would be prepared to recruit patients to a randomized trial comparing full dose IV heparin with control in patients with acute ischemic stroke and AF. Furthermore, it would require a governmental funding agency such as the National Institutes of Health (NIH) or United Kingdom Medical Research Council (UK MRC) to support an appropriately-sized trial (because IV heparin is a generic drug with no major commercial potential). However, an IV heparin trial would be competing with other, much more promising stroke interventions for government funding. A trial of IV heparin is not enough of a “burning question” that it would be likely to win in a competition for funding.
So what to advise? Generally, don’t choose IV heparin just because that’s what everyone else does or because you fear litigation. Stick to the evidence and be reasonable (ie, avoid heparin). Start aspirin immediately, because it is effective, safe, simple, needs no complex monitoring and can be used in even the most resource-poor health systems. When the period of highest risk of intracranial bleeding/hemorrhagic conversion of the infarct has passed, start oral anticoagulants and stop the aspirin.
- Received July 13, 2006.
- Accepted August 11, 2006.
Hart RG, Palacio S, Pearce LA. Atrial fibrillation, stroke, and acute antithrombotic therapy: analysis of randomized clinical trials. Stroke. 2002; 33: 2722–2727.
Moussouttas MM, Lichtman JH, Krumholtz HM, Cerese J, Brass L. The use of heparin anticoagulation in acute ischemic stroke among academic medical centers. Stroke. 1999; 30: 265.
Al Sadat A, Sunbulli M, Chaturvedi S. Use of intravenous heparin by North American neurologists: do the data matter? Stroke. 2002; 33: 1574–1577.
Grips E, Daffertshofer M, Hennerici M. Banning anticoagulation in stroke or consequence of poor study design. Stroke. 2003; 34: 837–839.
Moonis M, Fisher M. Considering the role of heparin and low-molecular-weight heparins in acute ischemic stroke. Stroke. 2002; 33: 1927–1933.
Coull BM, Williams LS, Goldstein LB, Meschia JF, Heitzman D, Chaturvedi S, Johnston KC, Starkman S, Morgenstern LB, Wilterdink JL, Levine SR, Saver JL; Joint Stroke Guideline Development Committee of the American Academy of Neurology/American Stroke Association. Anticoagulants and antiplatelet agents in acute ischemic stroke: report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association (a division of the American Heart Association). Stroke. 2002; 33: 1934–1942.