Few afibbers benefit from warfarin
BOSTON, MASSACHUSETTS. Despite several studies unequivocally showing that anticoagulation therapy does not benefit, but may actually harm, lone afibbers with none or, at the most, one risk factor for ischemic stroke, warfarin is still widely prescribed for this patient population. A study just released by a team from Massachusetts General Hospital, University of California, and Kaiser Permanente of Northern California will, hopefully, go a long way towards banishing the excessive prescription of warfarin (Coumadin) for lone afibbers. The California study involved 13,559 patients with nonvalvular atrial fibrillation who were followed for 6 years, accumulating a total of over 66,000 person-years of actual experience on warfarin usage in AF. At entry to the study about 53% of the patients were on warfarin.

In past studies aimed at proving the benefits of warfarin therapy among afibbers the focus has been entirely on the prevention of ischemic stroke with no, or very scant, attention paid to the harm done by the drug. The California study takes a bold step forward in this respect in that it introduces a new concept "net clinical benefit". In other words, it considers both the benefit (reduction in ischemic stroke) and harm (increase in hemorrhagic stroke) in administering the drug. Net clinical benefit (NCB) is defined as:

NCB = (TE rate off warfarin – TE rate on warfarin) – W x (ICH rate on warfarin – ICH rate off warfarin)

  • TE rate is the annualized rate of thromboembolic events (ischemic stroke and systemic emboli)
  • W is a weighting factor designed to reflect the fact that the consequences of a hemorrhagic stroke (intracranial bleeding) is far more serious than that of an ischemic stroke. The authors used a W equal to 1.5.
  • ICH rate is the annualized rate of intracranial bleeding (incl. hemorrhagic stroke).
During the 6-year follow-up there were 407 thromboembolic events, 93% of which were ischemic strokes, in the total group treated with warfarin vs. 685 in patients not receiving warfarin, resulting in annualized TE rates of 1.25% and 2.29% respectively. ICH rates were 0.33% and 0.57% respectively. Not surprisingly, the net clinical benefit of warfarin therapy was highest for patients with a serious risk of stroke and negligible to negative in other cases. Thus, afibbers with a CHADS2 score (this score assigns 1 point each for congestive heart failure, hypertension, age 75 years or older and diabetes, and 2 points for previous stroke of TIA) of 0 (no risk factors for stroke) had a NCB of –0.11% indicating that for this group, which includes most lone afibbers, warfarin therapy is actually more likely to be harmful than beneficial. The likelihood of harm was particularly strong among those aged 65 years or less where the NCB was –0.25%. On the other hand, for patients over the age of 85 years, NCB was a positive 2.34% and for those who had already suffered a stroke it was 2.48%.

The researchers conclude that the net benefit of warfarin therapy is essentially zero in atrial fibrillation patients with a CHADS2 score of 0 or 1, i.e. with, at the most, one risk factor for ischemic stroke.

In an accompanying editorial Drs. Robert Hart and Jonathan Halperin make the following salient statements:

  • The authors failed to include major gastrointestinal bleeding as a negative impact of warfarin therapy. Had they done so the NCB would likely have been smaller.
  • The annual rate of ischemic stroke among afibbers with one stroke risk factor was only 1.2% even without warfarin therapy. Editor's note: This number is far lower than the 4 to 5% per year reported in the original studies aimed at proving the benefits of warfarin in stroke prevention.
  • Participants with CHADS2 scores of 0 and 1, about half of the afibbers in the study, gained no benefit from warfarin.
Singer, DE, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Annals of Internal Medicine, Vol. 151, September 1, 2009, pp. 297-305
Hart, RG and Halperin, JL. Do current guidelines result in overuse of warfarin anticoagulation in patients with atrial fibrillation? Annals of Internal Medicine, Vol. 151, September 1, 2009, pp. 355-56

Editor's comment: Ever since I first began researching the role of warfarin in stroke prevention among lone afibbers, I invariably arrived at the conclusion that for a lone afibber with none or, at most, one risk factor for ischemic stroke warfarin therapy is contra-indicated. Not only is warfarin not beneficial in this patient group, but considering its many potential adverse effects (hemorrhagic stroke, major gastrointestinal bleeding, serious interactions with foods and herbs, arterial calcification, osteoporosis, skin necrosis, and serious eye damage in patients with age-related macular degeneration) and the difficulty in maintaining INR within the prescribed range, it is likely to cause more harm than good. It is indeed rewarding to see this conclusion confirmed by such a large and well-designed study.

Incidentally, in my book Thrombosis and Stroke Prevention written 5 years ago I introduced the idea of net clinical benefit (NCB) (pages 66-68) and found that an afibber with a CHADS2 score of 0 (no risk factors) would have a NCB of –0.01%. Had I used a weighting factor of 1.5 for hemorrhagic stroke, the NCB would have been –0.13% for an afibber with no risk factors; very close to the –0.11% quoted in the California study.