EDINBURGH, SCOTLAND. With 3 new anticoagulants recently approved for stroke prevention in atrial fibrillation (AF), it is perhaps not surprising that the push is on to increase the number of patients who are prescribed warfarin, dabigatran, rivaroxaban or apixaban. At a recent consensus conference organized by the Royal College of Physicians of Edinburgh, the participants approved the following statement:

Screening for AF in people of 65 or older satisfies the UK National Screening Committee criteria for a screening programme and such a national screening programme should be undertaken in the UK.

The conference participants also agreed that the most cost effective screening method would be routine pulse checking of people over the age of 65 years by GPs, followed by electrocardiogram examination for those with an irregular pulse.

Among other statements made at the conference: �

• Atrial fibrillation is easily treated with drugs such as warfarin. Obviously the conference participants had no personal experience with AF or they would have realized that for the majority of afibbers it is the vastly diminished quality of life that is the main problem and this certainly is not �fixed� by prescribing anticoagulants. As Professor Philippe Coumel MD stated in the foreword to my book, �for the patient the symptom (atrial fibrillation) is the major issue whereas the physician�s main concern is the potential arrhythmia-related risk, in particular stroke rather than discomfort.�

• Aspirin is ineffective in stroke prevention in people with atrial fibrillation and should not be used. Aspirin may have some minor benefit in the prevention of strokes involving blockages associated with platelet-rich clots (thrombi) as it prevents platelet aggregation and subsequent clot formation. However, the blood clots (cardiogenic emboli) associated with AF originate in the left atrium or left atrial appendage and are fibrin-rich and their formation is not prevented by aspirin. This is not really rocket science, but it is good to see it finally recognized by stroke specialists.

• It is estimated that 5000 strokes (presumably ischemic) and 2000 premature deaths (presumably per year) could be avoided through effective detection and treatment. When considering this statement it is hugely important to realize that treatment with warfarin or any of the newer anticoagulants carry significant risks (hemorrhagic stroke and major bleeding).

A study carried out by a team of researchers from Massachusetts General Hospital, University of California, and Kaiser Permanente of Northern California casts serious doubt on the benefits of prescribing warfarin to AF patients at low risk for ischemic stroke. The study involved 13,559 patients with non-valvular 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) are 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 zero (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.[1]
Christie, Bryan. People over 65 should be screened for atrial fibrillation, say stroke specialists. British Medical Journal, Vol. 344, 2012, p. e1644

Editor�s comment: Unfortunately, as is the case for breast and prostate cancer, it is likely that a routine screening program for atrial fibrillation will lead to over-treatment and, as discussed above, a negative net clinical benefit, particularly when it comes to lone afibbers with no or, at the most, one risk factor for ischemic stroke.
[1] 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