Efficacy and safety of prolonged-release lappaconitine hydrobromide in premature atrial contractions: pilot observational study

Aim. To evaluate the efficacy and safety of the prolonged-release formulation of lappaconitine hydrobromide at the minimum dose of 25 mg twice daily in patients with premature atrial contractions (PACs) and no structural heart disease. 

Methods. This retrospective open-label non-randomized observational study included 52 patients (20 men) aged 31-79 years with symptomatic PACs and/or paroxysmal atrial fibrillation requiring antiarrhythmic therapy. All patients underwent two Holter ECG recordings: before treatment initiation and after 2-3 weeks of therapy with prolonged-release lappaconitine hydrobromide 25 mg twice daily. All quantitative indices of atrial ectopic activity were normalized to 24 hours. Efficacy was assessed by changes in the number of single, paired, and grouped PACs, episodes of paroxysmal focal atrial tachycardia (AT), the ectopic burden index, and the distribution of responders. Safety was assessed by changes in heart rate, P-wave, QRS complex, PQ, QT and QTc intervals duration. Analysis of individual forms of atrial ectopic activity was performed only in patients in whom the corresponding types of arrhythmia were present at baseline and for whom complete data were available to assess their changes during therapy.

Results. Therapy was associated with a statistically significant reduction in all forms of atrial ectopic activity, including single PACs, paired PACs, grouped PACs, and episodes of paroxysmal focal AT (all p<0.001). In most patients, the reduction in arrhythmia frequency was ≥75%. A similar effect was observed in the subgroup with a high baseline PAC burden (>500 PACs per 24 hours). Heart rate decreased moderately; a statistically significant but clinically insignificant increase in the PQ interval was observed. No significant changes were found in P-wave duration, QRS duration, or QT and QTc intervals.

Conclusion. The prolonged-release formulation of lappaconitine hydrobromide at the minimum daily dose of 50 mg provides a statistically significant reduction in atrial ectopic activity in patients without structural heart disease and is characterized by a favorable safety profile when administered twice daily.

1. Bokeria LA, Golukhova EZ, Popov SV, et al. 2020 Clinical practice guidelines for supraventricular tachycardia in adults. Russian Journal of Cardiology. 2021;26(5): 4484. (In Russ.). https://doi.org/10.15829/1560-4071-2021-4484.

2. Popov SV, Davtyan KV, Shubik YuV, et al. Supraventricular tachycardias. Clinical guidelines 2025. Russian Journal of Cardiology. 2025;30(7): 6448. (In Russ.). https://doi.org/10.15829/1560-4071-2025-6448.

3. Shubik YuV, Tikhonenko VM. Holter monitoring in arrhythmias. In 2 volumes. Saint Petersburg; 2019 (In Russ.).

4. Tikhonenko VM, Tulintseva TE, Lyshova OV, et al. Heart rhythm and conduction disorders in healthy individuals. Journal of Arrhythmology. 2018;91: 11-20 (In Russ.).

5. Lin CY, Chang SL, Lin YJ, et al. Prognostic significance of premature atrial complexes burden in prediction of longterm outcome. J Am Heart Assoc. 2015;4(9): e002192. https://doi.org/10.1161/JAHA.115.002192.

6. Hsu NW, Tsao HM, Chen HC, et al. Different impacts of atrial fibrillation and cardiac premature contractions on the health-related quality of life in elderly people: the Yilan study. Tohoku J Exp Med. 2016;238(1): 75-83. https://doi.org/10.1620/tjem.238.75.

7. He B, Li Y, Huang W, et al. Mapping and ablation of isolated frequent symptomatic premature atrial contractions in patients with structurally normal heart. Front Cardiovasc Med. 2022;9: 862659. https://doi.org/10.3389/fcvm.2022.862659.

8. Riesinger L, Siebermair J, Wakili R. Mapping strategies and ablation of premature atrial complexes. Herzschrittmacherther Elektrophysiol. 2021;32(1): 9-13. https://doi.org/10.1007/s00399-021-00744-9.

9. Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998;339(10): 659- 666. https://doi.org/10.1056/NEJM199809033391003.

10. Prasitlumkum N, Rattanawong P, Limpruttidham N, et al. Frequent premature atrial complexes as a predictor of atrial fibrillation: systematic review and meta-analysis. J Electrocardiol. 2018;51(5): 760-767. https://doi.org/10.1016/j.jelectrocard.2018.07.004.

11. Guichard JB, Guasch E, Roche F, et al. Premature atrial contractions: a predictor of atrial fibrillation and a relevant marker of atrial cardiomyopathy. Front Physiol. 2022;13: 971691. https://doi.org/10.3389/fphys.2022.971691.

12. Sasaki N, Yamamoto T, Sugiyama K, et al. High burden of premature atrial contractions predicts atrial fibrillation. Circ J. 2021;85(8): 1343-1348. https://doi.org/10.1253/circj.CJ-20-1277.

13. Larsen BS, Kumarathurai P, Falkenberg J, Nielsen OW, Sajadieh A. Excessive atrial ectopy and short atrial runs increase the risk of stroke beyond incident atrial fibrillation. J Am Coll Cardiol. 2015;66(3): 232-241. https://doi.org/10.1016/j.jacc.2015.05.018.

14. Acharya T, Tringali S, Bhullar M, et al. Frequent atrial premature complexes and their association with risk of atrial fibrillation. Am J Cardiol. 2015;116(12): 1852-1857. https://doi.org/10.1016/j.amjcard.2015.09.025.

15. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2021;42(5): 373-498. https://doi.org/10.1093/eurheartj/ehaa612.

16. Van Gelder IC, Rienstra M, Bunting KV, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2024;45(36): 3314-3414. https://doi.org/10.1093/eurheartj/ehae176.

17. Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/ EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Europace. 2018;20(1): e1-e160. https://doi.org/10.1093/europace/eux274.

18. January CT, Wann LS, Calkins H, et al. 2019 AHA/ ACC/HRS focused update of the 2014 guideline for the management of patients with atrial fibrillation. Circulation. 2019;140(2): e125-e151. https://doi.org/10.1161/CIR.0000000000000665.

19. Hillmann HAK, Soltani S, Mueller-Leisse J, et al. Cardiac rhythm monitoring using wearables for clinical guidance before and after catheter ablation. J Clin Med. 2022;11(9): 2428. https://doi.org/10.3390/jcm11092428.

20. Palmisano P, Accogli M, Zaccaria M, et al. Expert opinion on continuous rhythm monitoring of patients with atrial fibrillation for candidates or patients who have already undergone ablation. Int J Cardiol. 2020;304: 49-55. https://doi.org/10.1016/j.ijcard.2020.02.001.

21. Unni RR, Prager RT, Odabashian R, et al. Rhythm-monitoring strategy and arrhythmia recurrence in atrial fibrillation ablation trials: a systematic review and meta-regression analysis. CJC Open. 2022;4(5): 449-465. https://doi.org/10.1016/j.cjco.2022.02.001.

22. Damiano RJ Jr, Badhwar V, Acker MA, et al. Detection of atrial fibrillation after surgical ablation: conventional versus continuous monitoring. Ann Thorac Surg. 2016;101(1): 42-47. https://doi.org/10.1016/j.athoracsur. 2015.07.039.

23. Aguilar M, Xue X, Alqarawi W, et al. Influence of monitoring strategy on assessment of ablation success and postablation atrial fibrillation burden. Circulation. 2022;145(1): 21-30. https://doi.org/10.1161/CIRCULATIONAHA.121.056071.

24. Schwab AC, Abugattas AN, Frontera A, et al. Rhythm monitoring, success definition, recurrence, and anticoagulation after atrial fibrillation ablation: results of an EHRA survey. Europace. 2023;25(2): euac194. https://doi.org/10.1093/europace/euac194.

25. Verma A, Champagne J, Sapp J, et al. Discerning the incidence of symptomatic and asymptomatic episodes of atrial fibrillation before and after catheter ablation (DISCERN AF): a prospective, multicenter study. JAMA Intern Med. 2013;173(2): 149-156. https://doi.org/10.1001/jamainternmed.2013.1561.

26. Simantirakis EN, Papakonstantinou PE, Chlouverakis GI, et al. Asymptomatic versus symptomatic episodes in patients with paroxysmal atrial fibrillation via long-term monitoring with implantable loop recorders. Int J Cardiol. 2017;231: 125-130. https://doi.org/10.1016/j.ijcard.2016.12.025.

27. Hermans ANL, Gawalko M, Dohmen L, et al. Longterm intermittent versus short continuous heart rhythm monitoring for atrial fibrillation recurrence after ablation. Int J Cardiol. 2021;329: 105-112. https://doi.org/10.1016/j.ijcard.2020.12.022.

28. Hermans ANL, Gawalko M, Dohmen L, et al. Mobile health solutions for atrial fibrillation detection and management: a systematic review. Clin Res Cardiol. 2022;111(5): 479-494. https://doi.org/10.1007/s00392-021-01941-9.

29. Dan GA, Martinez-Rubio A, Agewall S, et al. Antiarrhythmic drugs-clinical use and clinical decision making: a consensus document from the European Heart Rhythm Association and European Society of Cardiology Working Group on Cardiovascular Pharmacology. Europace. 2018;20(5): 731-732an. https://doi.org/10.1093/europace/eux373.

30. Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984;24(4): 129-147. https://doi.org/10.1002/j.1552-4604.1984.tb01822.x.

31. Farinha JM, Lopes LR, Providência R, et al. Frequent premature atrial contractions as a signalling marker of atrial cardiomyopathy, incident atrial fibrillation, and stroke. Cardiovasc Res. 2023;119(2): 429-440. https://doi.org/10.1093/cvr/cvac054.

32. Meng L, Li X, Li J, et al. Premature atrial contractions and the risk of incident atrial fibrillation: a systematic review and meta-analysis. Front Cardiovasc Med. 2022;9: 971691. https://doi.org/10.3389/fcvm.2022.971691.

33. Porterfield JG, Porterfield LM. Therapeutic efficacy and safety of oral propafenone for atrial fibrillation. Am J Cardiol. 1989;63(1): 114-116. https://doi.org/10.1016/0002-9149(89)91091-6.

34. Pritchett ELC, McCarthy EA, Wilkinson WE. Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy. Ann Intern Med. 1991;114(7): 539-544. https://doi.org/10.7326/0003-4819-114-7-539.

35. Meinertz T, Lip GYH, Lombardi F, et al. Efficacy and safety of propafenone sustained release in the prophylaxis of symptomatic paroxysmal atrial fibrillation (ERAFT study). Am J Cardiol. 2002;90(12): 1300-1306. https://doi.org/10.1016/S0002-9149(02)02867-9.

36. Alboni P, Botto GL, Baldi N, et al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-inthe-pocket” approach. N Engl J Med. 2004;351(23): 2384-2391. https://doi.org/10.1056/NEJMoa041233.

37. Kishore AG, Leier CV, Magorien RD. Guidelines for the use of propafenone in treating supraventricular arrhythmias. Clin Cardiol. 1995;18(10): 591-596.

38. Alboni P, Botto GL, Boriani G, et al. Intravenous administration of flecainide or propafenone in patients with recent-onset atrial fibrillation does not predict adverse effects during “pill-in-the-pocket” treatment. Heart. 2010;96(7): 546-549. https://doi.org/10.1136/hrt.2009.187963.

39. Aliot E, Capucci A, Crijns HJ, Goette A, Tamargo J. Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace. 2011;13(2): 161-173. https://doi.org/10.1093/europace/euq382.

40. Echt DS, Ruskin JN. Use of flecainide for supraventricular arrhythmias. Am J Cardiol. 1990;65(18): 33B-39B.

41. Khan IA. Oral loading single dose flecainide for pharmacological cardioversion of recent-onset atrial fibrillation. Int J Cardiol. 2003;87(2-3): 121-128. https://doi.org/10.1016/S0167-5273(02)00467-9.

42. Capucci A, Villani GQ, Aschieri D, et al. Safety of oral flecainide for the conversion of recent-onset atrial fibrillation in out-of-hospital practice. Am J Cardiol. 1992;70(1): 69-72.

43. Condori Leandro EI, Lebedev DS, Mikhaylov EN. Therapeutic potential of flecainide for cardiac arrhythmias: a short review of studies and clinical recommendations. Journal of Arrhythmology. 2024;31(3): e1-e7 (In Russ.). https://doi.org/10.35336/VA-1397.

44. Korkushko OV, Shatilo VB, Moroz GZ, Shatilo TV. Antiarrhythmic efficacy and hemodynamic effect of ethacizine in middle-aged and elderly patients with ischemic heart disease and extrasystole. Klinicheskaya Meditsina. 1989;67(3): 74-78 (In Russ.)

45. Tsaregorodtsev DA, Okisheva EA, Gracheva EI, et al. The new approach to efficiency and safety evaluation of etacizin in patients without morphological heart pathology. Cardiology and Cardiovascular Surgery. 2014;7(2): 89-96 (In Russ.).

46. Lozinskii LG, Kalinin VN, Ardasheva NV, et al. Results of the treatment of paroxysmal atrial fibrillation with ethacizine. Kardiologiia. 1989;29(8): 57-61 (In Russ.).

47. Belyalov FI, Butorin NN, Kuznetsov VA, et al. Antiarrhythmic efficacy of ethacizine in patients with supraventricular extrasystole. Journal of Arrhythmology. 2005;40: 25-30 (In Russ.).

48. Archakova OA, Bagaeva NS, Komarov TN, et al. Pharmacokinetics study of the long-acting form of lappaconitine hydrobromide (Allaforte®). Drug Development and Registration. 2022;11(1): 140-147. (In Russ.). https://doi.org/10.33380/2305-2066-2022-11-1-140-147.

49. Revishvili ASh, Golitsyn SP, Aksentiev SB, et al. Comparative study of extended-release lappaconitine hydrobromide (Allaforte®) and propafenone in patients with paroxysmal atrial fibrillation. Vrach. 2024;35(1): 20-26. (In Russ.). https://doi.org/10.29296/25877305-2024-01-04

50. Erlikh AD. The study of evidence base for the use of lappaconitine hydrobromide in patients with atrial fibrillation. Kardiologiia. 2016;56(3): 48-53. (In Russ.). https://doi.org/10.18565/cardio.2016.3.48-53.

51. Vakhitova YuV, Farafontova EI, Khisamutdinova RYu, et al. To the mechanisms of antiarrhythmic action of Allapinine. Bioorganicheskaya Khimiya. 2013;39(1): 105-116. (In Russ.). https://doi.org/10.1134/S1068162013010111.

52. Kanorskiy SG, Shubik YuV. Class Ic antiarrhythmic drugs in clinical practice: the role of lappaconitine hydrobromide. Vrach. 2025;36(3): 32-38. (In Russ.). https://doi.org/10.29296/25877305-2025-03-06.