LAA closure remains noninferior to direct oral anticoagulants over long term
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Among patients with atrial fibrillation at high risk for stroke, left atrial appendage closure remained noninferior to direct oral anticoagulation for preventing major CV and neurological events out to 4 years.
Results of the PRAGUE-17 long-term follow-up study presented at TCT 2021 also demonstrated fewer clinically relevant and nonprocedural clinically relevant bleeding events among patients who underwent LAA closure compared with those on medical therapy.
For the main PRAGUE17 trial, researchers enrolled patients with AF who were indicated for oral anticoagulation, had a history of bleeding requiring intervention or hospitalization, had a prior cardioembolic event while on oral anticoagulation and/or had a CHA2DS2-VASc score of at least 3 and a HAS-BLED score greater than 2. Participants were randomly assigned to undergo LAA closure or receive direct oral anticoagulation for the prevention of stroke, embolism, CV death, bleeding, or procedure-related complications.
For the present analysis, the researchers evaluated long-term outcomes of LAA closure compared with direct oral anticoagulation, with approximately 4 years of follow-up in each group and a total aggregate of 1,354 patient-years.
After a median follow-up of 3.5 years, LAA closure remained noninferior to direct oral anticoagulation for the primary endpoint of cardioembolic events, CV death, clinically relevant bleeding or procedure/device-related complications, with 8.6 events per 100 patient-years in the LAA group and 11.9 events per 100 patient-years in the medical therapy group in the intention-to-treat analysis (sHR = 0.81; 95% CI, 0.56-1.18; P for noninferiority = .006).
LAA was also noninferior to direct oral anticoagulation for preventing CV death, all stroke or transient ischemic attack.
For the outcomes of clinically relevant and nonprocedural clinically relevant bleeding, fewer cumulative events occurred in the LAA group: 4.3 vs. 5.9 clinically relevant bleeding events per 100 patient-years (sHR = 0.75; 95% CI, 0.44-1.27; P for Grays test = .29) and 3.4 vs. 5.9 clinically relevant bleeding events per 100 patient-years (sHR = 0.55; 95% CI, 0.31-0.97; P for Grays test = .038), according to the results.
“The long-term outcome for left atrial appendage closure was noninferior to direct oral anticoagulant treatment in high-risk patients with atrial fibrillation for preventing major cardiovascular and neurological events,” Pavel Osmancik, MD, PhD, senior physician in the department of arrhythmology at University Hospital Kralovske Vinohrady in Prague, Czech Republic, said during the presentation. “In the long-term, the rate of nonprocedural bleeding was reduced with the appendage closure strategy. We believe appendage closure may be considered as a nonpharmacological alternative to long-term anticoagulation in high-risk patients with atrial fibrillation.”
The results were simultaneously published in the Journal of the American College of Cardiology.
In a related editorial, Faisal M. Merchant, MD, assistant professor of electrophysiology at Emory University, contextualized the findings.
“When placing the longer-term results of PRAGUE-17 in clinical context, it is also important to bear in mind the challenges in interpreting a composite endpoint which includes both efficacy and safety events. ... When engaging in shared decision-making interactions with patients, it is crucial to be able to communicate the severity of the endpoints prevented and to understand whether [LAA closure] and [novel oral anticoagulation] are truly similarly efficacious. Unfortunately, the severity of ischemic and bleeding events in PRAGUE-17 is not reported,” Merchant wrote.
Both the researchers and Merchant said larger studies are needed to rigorously compare LAA closure with novel oral anticoagulation.
“Given the large number of patients with atrial fibrillation who merit stroke prevention therapy, it is incumbent upon us to really understand which therapies are most effective at preventing the endpoints which are most important to patients. But until such data are available, the longer-term results from PRAGUE-17 provide an important perspective on the challenges of evaluating late risks associated with SSE and bleeding in patients with atrial fibrillation,” Merchant wrote.
References:
- Osmancik P, et al. J Am Coll Cardiol. 2021;doi:10.1016/j.jacc.2021.10.023.
- Merchant FM. J Am Coll Cardiol. 2021;doi:10.1016/j.jacc.2021.10.022.
Perspective
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Oussama Wazni, MD, MBA
The key take-home message is that after a long period of follow-up, LAA closure was not inferior to oral anticoagulants. But there is nuance. The primary composite endpoint included stroke, embolism and bleeding. The reassuring part is that the risk for stroke or thromboembolism was similar in both arms, and that the bleeding occurred more in the anticoagulant arm, which is expected.
However, because the study was not powered to look at stroke itself, we have to be careful in interpreting these results. It is reassuring to know that with long-term follow-up, the risk for stroke and thromboembolic events is not higher in the LAA closure group than in the oral anticoagulation group.
In clinical practice, we close the LAA to prevent stroke and avoid long-term oral anticoagulation. In that respect, the findings confirm our approach. Of concern, we do not know what the incidence and risks for device-related thrombosis or leaks were. The authors said they intended to look at that, but because of the COVID-19 pandemic, a lot of patients had their transesophageal echocardiography canceled.
A small number of patients in the LAA closure arm (approximately 8.5%) ended up with long-term blood thinners. We need to better understand the reasons for this. Was it due to device-related thrombosis or leaks, and if so, we need to better understand the risks for device-related thrombosis and if it can be avoided altogether. We also need to know if it is reasonable to resume oral anticoagulation in a subset of patients, and which subsets. Are they patients at high risk for stroke for other reasons? Are they patient whom we know may develop device-related thrombosis? It would be nice to understand what this 8.5% is about.
There are three large studies in progress that may help clarify some of these issues. OPTION, which I have been leading, randomly assigned patients with AF after ablation to oral anticoagulation or LAA closure with Watchman. We have enrolled 1,600 patients and will follow them for 3 years. This will better inform us on the risk for stroke and bleeding in low-risk patients who have already had ablation for AF. Then there is the CHAMPION study of Watchman vs. oral anticoagulation and the CATALYST study of Amulet vs. oral anticoagulation. These each have more than 3,000 patients each and follow-up of 3 to 5 years. These will be the seminal studies that will inform us more closely on whether LAA closure will replace oral anticoagulation in most patients.
We also have to consider if there is a subgroup of patients who should be treated with LAA closure plus oral anticoagulation because of high risk. The LAAOS III study showed that clipping the LAA during surgery plus oral anticoagulation is better than oral anticoagulation alone; the risk for stroke was much lower in the group that got LAA closure. We are now working on LAAOS IV, which will hopefully inform us regarding percutaneous strategies; it will be LAA closure with Watchman plus oral anticoagulation vs. anticoagulation alone.
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Osmancik P, et al. Late-Breaking Clinical Trials Session II. Presented at: TCT Scientific Symposium; Nov. 4-6, 2021; Orlando, Florida (hybrid meeting).
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