Canadian trial data?

The recent RxFiles by Kosar et al¹ is an excellent and helpful review of oral anticoagulant management in atrial fibrillation (AF). However, some serious questions arise when looking at the “unexpected” high hemorrhagic stroke rates in the warfarin arms of these trials (RELY [Randomized Evaluation of Long-term Anticoagulation Therapy], ROCKET-AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in AF], and ARISTOTLE [Apixaban for Reduction in Stroke and Other ThromboemboLic Events in AF]), all of which were conducted multinationally with 39 to 45 countries participating, as opposed to a very low rate of hemorrhagic stroke experienced in the warfarin arm of the SPORTIF V (Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation V) trial (2 events in 1962 patients), which was a North American–only trial of the first novel oral anticoagulant, ximelagatran. Perhaps it would be helpful if the Canadian data from these subsequent trials were published. Is the difference in hemorrhagic stroke rates owing to the change in settings of these studies from North America (the most relevant context for Canadian family physicians) to a multinational arena? What are the differences in the elements of the HAS-BLED score between these studies? What are the ranges of these elements as well?

It only takes a few outlier patients taking acetylsalicylic acid, with uncontrolled hypertension and poor warfarin control, to create large differences in bleed rates. Second, the hemorrhagic stroke issue aside, warfarin is demonstrated to be superior to dabigatran for all other major end points using RELY’s own data when warfarin is managed properly and the average proportion of time the international normalized ratio is in therapeutic range is greater than 72.6%.² Why is so little attention paid to sensitivity analyses when discussing warfarin? With simple and inexpensive computerized decision support tools, it is possible to achieve time in the therapeutic range of greater than 80%. I believe our most important problem has been poor warfarin management, not warfarin itself. Perhaps a few dollars spent on computerized support tools would be better value for money than the hundreds of millions being spent on switching to novel oral anticoagulants, with no method of monitoring the degree of anticoagulation (a substantial compliance issue), no effective antidote, and no long-term track record.

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