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Clot Chronicles: Trial Takeaways from AHA 2021
Hello, this is Dr. Christian Ruff. I’m a cardiologist at Brigham and Women’s Hospital and Harvard Medical School. And today I’m welcoming you to the North American Thrombosis Forum’s AHA 2021 wrap-up. Some very exciting science presented at this year’s AHA.
I’d like to start with the GIRAF trial, a really important trial. We know atrial fibrillation has been associated with increasing dementia and cognitive impairment, and some of that was thought to be due to subclinical strokes or asymptomatic strokes. So there was a study conducted in 200 patients, in Brazil, looking at patients with atrial fibrillation with a CHA2DS2-VASc score of 1 and randomizing them to either dabigatran or warfarin. Remember dabigatran was the one NOAC that was actually statistically better than warfarin in reducing ischemic stroke, so the thought was maybe it’d be better at preventing dementia.
The results were very interesting in this study. There ended up being no difference in neuropsychologic testing, no difference between the onset of cognitive impairment or dementia in these patients. So it tells us that there likely is a more complicated story to dementia and atrial fibrillation patients, and choice of anticoagulant doesn’t necessarily influence that selection.
There was other very exciting research done in atrial fibrillation, two studies, one I’d like to highlight, the Fitbit Heart Study, and this used a novel software algorithm to detect – either a smartwatch or a fitness tracker – irregular heart rhythms that may be due to atrial fibrillation. This was a really large study enrolled 455,000 patients or subjects with a smartwatch or fitness tracker. And it detected an irregular heartrate in about 1% of overall patients and 4% of older individuals above the age of 65. And then when they got an ECG patch monitor, atrial fibrillation was detected 32% of the time in a patient who had an irregular heart rhythm on their tracker.
Now interestingly, once the subjects had an ECG patch, if they did have another irregular heart rhythm detection at that time, 98% of the individuals actually had atrial fibrillation at that time of the irregular heart rhythm. So I think this is a very important study, along with the Apple Heart Study that came before it, that tried to help us figure out how we’re going to employ these trackers or smartwatches to detect atrial fibrillation in high-risk patients. There’s certainly more work to be done. And this trial did not look at whether detecting atrial fibrillation early in these asymptomatic patients would improve treatment outcomes.
Another study that I know that is near and dear to a lot of my atrial fibrillation patients is the I-STOP study, which was looking to see whether triggers of atrial fibrillation – detection of triggers – could lower the incidence. And this was a very interesting study looked at 446 patients, and they performed remote mobile applicated-based trial where they were randomly assigned to either monitor AFib episodes without tracking their presumed triggers or to test whether the specific triggers caused the atrial fibrillation episodes. Now the primary endpoint of this study was actually quality of life, and there was no difference.
And so, tracking your triggers didn’t appear to decrease quality of life or decrease the quality of life metrics. But interestingly, those who tracked their symptoms, there was a reduction in the episodes of atrial fibrillation. And interestingly, the trigger that was most associated with AFib episodes was alcohol consumption. So that likely does play a role in AF burden. But near to my heart – since I’m a coffee drinker – caffeine consumption was not linked to an increased risk of AF episodes. So certainly some very exciting research there.
And the final study that I’d like to highlight is some really exciting late-breaking science regarding factor XI inhibitors. And we know our current anticoagulations – whether they’re factor X or factor II inhibitors – are really important advances compared to warfarin. Factor XI inhibitors are another mechanism that’s thought to be even safer, potentially, than our current platform of anticoagulation. And this was a trial, the AXIOMATIC-Total Knee Replacement study with one of these inhibitors, the oral milvexian, which was being compared to subcutaneous enoxaparin in patients undergoing elective knee arthroplasty. And this was a very important study, and they looked at a range of doses from 25 mg a day to 400 mg a day.
And they basically showed that compared to standard of care VTE prophylaxis with enoxaparin especially the higher doses of milvexian were very effective – reduced VTE, a composite of asymptomatic and symptomatic VTE, by close to 70%. And there wasn’t a dose-related effect on bleeding. So the bleeding rates in the study were very low and similar to the bleeding of low-molecular-weight heparin prophylaxis. So this is very exciting because these are the drugs that are going to be used in our atrial fibrillation patients. And so it offers a promise of having a very effective anticoagulant with bleeding rates that are even better than our current factor Xa and IIa inhibitors.
So again, it was a great American Heart Association 2021. And I look forward to sharing more clinical trial updates after our next meeting.