LAA Closure Non-Inferior to NOACs in Patients With AF at High Risk for Stroke

Decisions regarding thromboprophylaxis requires weighing the risk of stroke against the risk of bleeding in each patient.[3,4] Numerous risk assessment tools are available, including CHADS2, CHA2DS2-VASc, and HAS-BLED. American and European guidelines recommend the use of CHA2DS2-VASc, which considers sex, age, and history of congestive HF, hypertension, stroke/transient ischemic attack/thromboembolism, vascular disease, and diabetes mellitus.[3,4] Compared with other stroke risk assessment measures, this tool performed best in identifying patients at low risk of stroke who did not require anticoagulation therapy.[12] Oral anticoagulation is recommended in any patient with a score ≥2 on the CHA2DS2-VASc. In these patients, warfarin or the novel anticoagulants dabigatran, rivaroxaban, apixaban, or edoxaban can be considered, except in the setting of moderate to severe chronic kidney disease, where reduced doses of direct thrombin or factor Xa inhibitors are preferable.[4]
Decisions regarding thromboprophylaxis requires weighing the risk of stroke against the risk of bleeding in each patient.[3,4] Numerous risk assessment tools are available, including CHADS2, CHA2DS2-VASc, and HAS-BLED. American and European guidelines recommend the use of CHA2DS2-VASc, which considers sex, age, and history of congestive HF, hypertension, stroke/transient ischemic attack/thromboembolism, vascular disease, and diabetes mellitus.[3,4] Compared with other stroke risk assessment measures, this tool performed best in identifying patients at low risk of stroke who did not require anticoagulation therapy.[12] Oral anticoagulation is recommended in any patient with a score ≥2 on the CHA2DS2-VASc. In these patients, warfarin or the novel anticoagulants dabigatran, rivaroxaban, apixaban, or edoxaban can be considered, except in the setting of moderate to severe chronic kidney disease, where reduced doses of direct thrombin or factor Xa inhibitors are preferable.[4]
Researchers examined the 4-year outcomes of the PRAGUE-17 trial, which compared the effectiveness of LAA closure against NOACs for preventing cardioembolic events in AF.

For long-term prevention of major cardiovascular, neurological, or bleeding events, left atrial appendage (LAA) closure was non-inferior to non-warfarin oral anticoagulants (NOACs). These findings were presented at the Transcatheter Cardiovascular Therapeutics (TCT) conference, held on November 4 to 6, 2021, and were published in the Journal of the American College of Cardiology.

The PRAGUE-17 trial (ClinicalTrials.gov Identifier: NCT02426944) was an investigator-initiated, randomized, non-inferiority trial conducted at 10 centers in the Czech Republic between 2015 and 2019. Patients (N=402) with non-valvular atrial fibrillation (AF) with increased risk for bleeding or stroke were randomly assigned to receive LAA closure (n=201) or NOACs (n=201). The primary endpoint was the composite instance of stroke, transient ischemic attack, systemic embolism, clinically significant bleeding, cardiovascular death, or significant device- or peri-procedural-related complication at a median of 3.5 years.

Patients in the LAA closure and NOAC cohorts had a mean age of 73.4±6.7 and 73.2±7.2 years; 66.7% and 64.7% were men; 92.5% and 92.5% had hypertension; 41.3% and 35.8% had permanent AF; and 26.4% and 33.3% had paroxysmal AF, respectively.

A total of 187 ultimately underwent LAA closure, and procedure attempts were successful among 96.8%. Patients received an Amulet (61.3%), Watchman (35.9%), or Watchman-FLX (2.8%) device.

Among the NOAC cohort, most received 5 mg twice daily apixaban (79.1%), followed by 2.5 mg apixaban (16.4%), dabigatran (4.0%), or rivaroxaban (0.5%).

By year 4, the composite endpoint occurred among 24.4% of the LAA closure and 31.3% of the NOAC cohorts, which did not differ between groups (subdistribution hazard ratio [sHR], 0.81; 95% CI, 0.56-1.18; P =.27), indicating LAA closure was non-inferior to NOAC (P =.006).

Stratified by specific event, no group differences were observed for cardiovascular death (sHR, 0.68; 95% CI, 0.39-1.20; P =.19), stroke or transient ischemic attack (sHR, 1.14; 95% CI, 0.56-2.30; P =.72), stroke (sHR, 1.38; 95% CI, 0.63-3.03; P =.42), clinically-relevant bleeding (sHR, 0.75; 95% CI, 0.44-1.27; P =.28), non-cardiovascular death (sHR, 0.99; 95% CI, 0.55-1.77; P =.96), or all-cause death (sHR, 0.81; 95% CI, 0.54-1.22; P =.31).

For non-procedural clinically-relevant bleeding, LAA closure recipients had a decreased rate compared with NOAC recipients (3.41 vs 5.89; sHR, 0.55; 95% CI, 0.31-0.97; P =.039).

In a subgroup analysis, no differential effects were observed for age (P =.59); sex (P =.26); weight (P =.50); history of cardioembolic event (P =.28); history of bleeding (P =.58); center type (P =.47); or congestive heart failure, hypertension, age 75 years and older, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, or sex category (P =.98).

This study was underpowered to detect relative differences among the individual components of the primary endpoint.

“Among non-valvular patients with atrial fibrillation and at high risk for stroke and bleeding, the non-inferiority of LAAC to NOAC relative to the composite of cardioembolic events, CV death, significant procedure/device-related complications, or clinically-relevant bleeding, was maintained during long-term follow-up,” the study authors said.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Osmancik P, Herman D, Neuzil P, et al. Left atrial appendage closure versus non-warfarin oral anticoagulation in atrial fibrillation: 4-year outcomes of PRAGUE-17. J Am Coll Cardiol. Published online November 5, 2021. doi:10.1016/j.jacc.2021.10.023

This article originally appeared on The Cardiology Advisor