Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial

Abstract

Background and Aims Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers flecainide and propafenone (SCB) in patients with cardiovascular disease. SCB were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. Methods We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm-control therapy) and primary efficacy outcome (cardiovascular death, stroke and hospitalization for worsening of heart failure or acute coronary syndrome) during SCB-intake for ERC patients (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Results Flecainide or propafenone was given to 689 patients (age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with heart failure; 41 with prior myocardial infarction, CABG or PCI; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1,153 [237, 1,828] days). The primary efficacy outcome occurred less often in patients treated with SCB (3/100 (99/3,316) patient-years) than in patients who never received SCB (SCBnever 4.9/100 (150/3,083) patient-years, p < 0.001). There were numerically fewer primary safety outcomes in patients receiving SCB (2.9/100 (96/3,359) patient-years) than in SCBnever patients (4.2/100 (135/3,220) patient-years, adjusted p = 0.015). Sinus rhythm at 2 years was similar between groups (SCB 537/610 (88); SCBnever 472/579 (82)). Conclusion Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable heart failure. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org

Antiarrhythmic drugs in the era of atrial fibrillation ablation

“…In the current issue of Europace , Rillig et al 13 report on a post-hoc analysis of the EAST-AFNET 4 trial, focusing on the primary safety outcome (death, stroke, or serious adverse events related to rhythm-control therapy) and on the primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of HF or acute coronary syndrome) in the subgroup of 1395 patients treated with flecainide or propafenone for early rhythm control. The results show that the 689 patients treated with flecainide or propafenone at baseline had a high probability of being in sinus rhythm at 2 years, with no statistical differences vs. patients not assuming sodium channel blockers, and were less often treated with catheter ablation.…”

“…Obviously, these findings should be interpreted considering the specific setting of cardiology centres with known expertise in the field and with appropriate clinical and electrocardiographic checks (conduction intervals, QRS duration) after institution of AAD treatment, also including weekly short-term electrocardiographic recordings, as per study protocol. 6 , 13 Additionally, it should be stressed that the median age of patients treated with Class IC agents was 69 years and only 25% of the patients had an age >75, thus limiting the generalizability of study findings to the large amount of very old patients presenting AF in the real world, often affected by many co-morbidities and frailty. 16 , 17 …”