ESC 2023 — Prof Paulus Kirchhof (University Heart & Vascular Center Hamburg, DE) discusses the findings of the NOAH-AFNET 6 trial (NCT02618577).
NOAH-AFNET 6 (Atrial Fibrillation Network, Daiichi Sankyo Europe) was an investigator-initiated, prospective, randomised trial aiming to demonstrate that oral anticoagulation using the NOAC edoxaban is superior to current therapy in stroke prevention, systemic embolism and cardiovascular death in patients with atrial high rate episodes and stroke risk factors. 2608 patients were enrolled in the trial, which compared edoxaban to ASA or placebo.
The NOAH-AFNET 6 trial revealed that using oral anticoagulation in AHRE patients raises bleeding risk without reducing the combined outcome of stroke, systemic embolism, or cardiovascular death.
Expectedly, anticoagulation led to more bleeding. Surprisingly, both anticoagulated and non-anticoagulated groups showed low stroke rates. This underscores the need for ECG evidence of atrial fibrillation before starting anticoagulation.
What is the importance of NOAH-AFNET 6?
What was the study design and the eligibility criteria?
What are the key findings?
What are the take-home messages for practice?
How should these findings influence guidelines?
Recorded on-site at ESC Congress 2023, Amsterdam.
For more content from ESC Congress 2023 head to the Hot Line & Late-breaking Science Video Collection.
Editors: Mirjam Boros and Jordan Rance
Video Specialists: Dan Brent, Tom Green, Mike Knight, Oliver Miles
Hello. My name is Paulus Kirchof. I’m here at the ESC Congress 2023 in Amsterdam, and we are going to talk about the NOAH-AFNET 6 nonvitamin K antagonist oral anticoagulants in patients with atrial high rate episodes trial.
Importance of NOAH AFNET 6
Now, NOAH addressed an important question. Do patients with atrial high-rate episodes, short atrial arrhythmias that look and feel like atrial fibrillation but are picked up by implanted devices that monitor the heart rhythm day and night, benefit from anticoagulation or not. And the key finding is one that’s actually a relief for our patients. Patients with atrial high rate episodes do not need anticoagulation.
Study Design and Patient Baseline Characteristics
So NOAH AFNET 6 randomized 2536 patients with atrial high-rate episodes longer than six minutes without an upper limit for duration, and with clinical stroke risk factors to anticoagulation or no anticoagulation, the mean age of the patients was 77.5 years. The median CHA2DS2-VASc score was 4. So they are a population of patients that would clearly be at high stroke risk if they had atrial fibrillation. The randomization to no anticoagulation, and it was a double-blind, double-dummy trial. So patients randomized to no anticoagulation received either a placebo or if they had an accepted indication for aspirin. They received aspirin 100mg per day. Patients randomized to anticoagulation received edoxaban in the dose approved for stroke prevention and atrial fibrillation. All patients were followed up until the end of the trial. All patients changed from studied medication to open-label anticoagulation when they had ECG-documented atrial fibrillation.
The primary efficacy outcome is the classical outcome composite of stroke, systemic embolism, and cardiovascular death. And anticoagulation does not reduce this outcome compared to no anticoagulation. And when you dig into the numbers, the surprising part of it is the low stroke rate without anticoagulation. Patients randomized in NOAH not treated with anticoagulation had a stroke rate of 1.1% per year. That is lower than the stroke rate on anticoagulation in patients with atrial fibrillation. On the other hand, as expected, anticoagulation increased the risk of major bleeding or death, a 30% increase. And that was statistically significant. So that we can conclude that anticoagulation increases bleeding as expected, but does not prevent cardiovascular events unexpected in patients with atrial heart rate episodes.
It’s good news for our patients. We didn’t know whether patients with atrial high rate episodes needed anticoagulation or not. Some of us thought that they need anticoagulation because these episodes look like atrial fibrillation and feel like atrial fibrillation. But now we know that we can stay calm, that we don’t need to treat these patients until they develop ECG-documented atrial fibrillation.
How these Findings Should Influence Guidelines
Now, I think this is the first randomized evidence in this area, so it reinforces the message that you find in the current ESC guidelines that you should not start treatment for atrial fibrillation before atrial fibrillation is diagnosed. So I think this is an important message for guidelines. I do think there is also a real signal that we need more research because obviously, the stroke rate wasn’t zero. There were systemic emboli, cardiovascular deaths. There are potentially preventable events and we need research to understand who in the population of patients with atrial heart rate episodes is at risk of these events.”