To Anticoagulate or Not in Subclinical AF: ARTESiA

John Mandrola and ARTESiA investigator Jeff Healey discuss the results and how they compare with the NOAH-AFNET-6 data on the use of DOACs in patients with short-duration AF.
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John M. Mandrola, MD: Hi everyone. This is John Mandrola from theheart.org | Medscape Cardiology. I'm here at the American Heart Association meeting in Philadelphia, and I'm excited to have Professor Jeff Healey from McMaster University, who was a primary investigator of the ARTESIA trial. ARTESIA is a really important trial because it addresses the question of what to do with patients who have short-duration subclinical atrial fibrillation (AF).
Jeff, welcome, and thanks for being with us.
Jeff S. Healey, MD, MSc: Thanks for the invite, John.
Mandrola: Tell us about what you found right off the bat, and then we'll go into the details.
Healey: In patients with pacemakers and implantable cardioverter-defibrillators, we found that among those with 6 minutes to 24 hours of subclinical AF, apixaban reduced the risk for stroke or embolism by approximately one third, with about a 50% reduction in large strokes that were disabling or fatal. To balance that, there was also an increase in the risk for major bleeding, which was a hazard ratio of 1.8 in an on-treatment analysis.
Aspirin as Control
Mandrola: Just a few weeks ago, we heard about NOAH-AFNET 6, which was edoxaban vs placebo, but 50% of that control arm was on aspirin. Why did you pick aspirin as the control? How does that influence the interpretation of these lower stroke rates and higher bleeding rates?
Healey: Aspirin was based on the patients themselves. At the beginning of the trial, prior to randomization, two thirds of our patients took an antiplatelet agent: aspirin, clopidogrel, or something else. This is the baseline and why we chose this as a comparator.
Also, as you recall, there's a difference between NOAH and ARTESIA here, and it's borne out of the difference between the American and the European approach to AF from 10 to 15 years ago. For many low-risk individuals in North America, we used aspirin. There was this expectation when we approached sites to participate that we have to try something with our patients who have this. There was this culture of using low-dose aspirin here in America that wasn't present in Europe, as they had abandoned it from their guidelines much earlier. I think that's why there is the difference between the two trials.
In terms of the effect, aspirin will possibly modestly reduce the risk for stroke. The meta-analysis suggests that at most, it's a 20% reduction, so not a big reduction, but of course, it is associated with a risk for bleeding and so would increase it compared with placebo. One third to one half of individuals were different between the trials where the control arm wasn't active therapy in NOAH, where it was aspirin across the board with ARTESIA.
Mandrola: What kind of patients were in ARTESIA?
Healey: First of all, this is a very common problem. You and I are both electrophysiologists. If you take those older than 65 years with hypertension, roughly one third will have this. This is common. Episodes had to be 6 minutes to 24 hours. We didn't allow any longer episodes, unlike NOAH. Furthermore, if during the course of the trial patients developed longer episodes, they were taken off study medication and treated with an anticoagulant.
We were looking for an enriched population, right? Because this is lower risk than clinical AF, we went for a higher-risk group, so a minimum CHA2DS2-VASc score of 3. We did allow patients with prior stroke or who are older than 75 years as a sole risk factor because those are such important risk factors. That's the population that we studied.
Mandrola: The CHA2DS2-VASc entry criterion was a score of 3, but it was actually higher in enrolled patients.
Healey: Minimum 3. There were some patients with very high CHA2DS2-VASc scores.
Mandrola: What was the median duration of the episodes? How short?
Healey: It's 1.5 hours, so that's shorter than NOAH, which speaks to the difference in the upper cutoff that we used that they didn't use, and shorter than in the observational trials like ASSERT, which probably speaks to some degree of selection bias that we had here.
Stroke Risk in Subclinical AF vs Clinical AF
Mandrola: We've all been discussing in our groups that this is a really low stroke rate. We saw that in NOAH, and of course, the hazard ratio for NOAH was definitely favoring the direct-acting oral anticoagulant (DOAC), but it didn't reach statistical significance because the stroke rates were low. You also found low stroke rates, even with high CHA2DS2-VASc scores. There's something different about this subclinical AF.
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