Rate vs Rhythm Control in Atrial Fibrillation

Rate vs Rhythm Control in Atrial Fibrillation

Rate vs rhythm control as a management strategy in atrial fibrillation has been a long standing topic for debate. Though at one look rhythm control would appear to be the ideal strategy, long term adverse effects of the currently available medications for rhythm control is the often cited down side. AFFIRM [1] and RACE [2] trials were the main reason for the debate as they failed to show any benefit for the rhythm control strategy. AF-CHF trial in those with AF and congestive heart failure also failed to show any advantage for the rhythm control strategy [3]. But there have been important criticisms as well [4]. In AFFIRM, only 45% of the eligible patients were randomized to a rate vs rhythm control strategy. Nearly two thirds in the rhythm control strategy were on amiodarone and only 14 had catheter ablation. Many were not in sinus rhythm or anticoagulated.

It was the negative results of the trials that caused rhythm control strategy which needs more skill in the use of antiarrhythmic drugs and can cause proarrhythmia or adverse effects, was relegated to the back stage. So it is clear that it was not rhythm control which was inferior, but the adverse effects of the currently available medications for rhythm control, which was inferior. That is how the strategy of rhythm control by catheter ablation was thought of as a possible better strategy, though technically more challenging, not uniformly effective and having significant risk of complications.

CASTLE-AF randomized 363 patients with atrial fibrillation and left ventricular ejection fraction of 35% or less, NYHA class II-IV heart failure and having an implanted defibrillator to either catheter ablation or medical therapy with rate or rhythm control [5]. The study documented that catheter ablation for AF in patients with heart failure was associated with a significantly lower rate of a composite endpoint of death from any cause or hospitalization for worsening heart failure, than medical therapy.

CABANA Trial randomized 2204 patients with AF aged 65 years or more and those below 65 years with one or more risk factors for stroke for catheter ablation with pulmonary vein ablation or drug therapy with rate or rhythm control. Among the subjects of CABANA trial 35% had NYHA class above II at baseline. Substudy of these patients with stable heart failure showed that catheter ablation produced clinically important improvements in survival, freedom from recurrence of AF and quality of life relative to drug therapy [6]. But the full cohort of the CABANA trial did not show a significant reduction in the primary composite end point of death, disabling stroke, serious bleeding or cardiac arrest [7]. The study authors noted that lower than expected event rates and treatment crossovers could have affected the results of the trial.

EAST-AFNET 4 trial had 2789 patients with early atrial fibrillation and cardiovascular conditions [8]. In the rhythm control arm, either drug therapy or catheter ablation could be used. The study was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow up per patient. They concluded that early rhythm control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions. Inclusion criteria were AF diagnosed within 12 months of enrollment, age above 75 years, previous transient ischemic attack or stroke or those who had two of the following criteria: age above 65 years, female gender, heart failure, hypertension, diabetes mellitus, severe coronary artery disease, chronic kidney disease stage 3 or 4, left ventricular hypertrophy defined as diastolic septal thickness of more than 15 mm.

Overall, it appears that rhythm control strategy in AF may be better in those with heart failure and in those with associated cardiovascular conditions and early AF. In asymptomatic persons and in elderly with longstanding atrial fibrillation and markedly enlarged left atria, rhythm control strategy may not be ideal. Though rate control strategy could be with beta blockers and calcium channel blockers, latter are better avoided in those with heart failure [9].

References

1. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1825-33. doi: 10.1056/NEJMoa021328. PMID: 12466506.
2. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ; Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1834-40. doi: 10.1056/NEJMoa021375. PMID: 12466507.
3. Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM, Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH, Lambert J, Le Heuzey JY, O’Hara G, Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG, Thibault B, Waldo AL; Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008 Jun 19;358(25):2667-77. doi: 10.1056/NEJMoa0708789. PMID: 18565859.
4. Prystowsky EN. Rate Versus Rhythm Control for Atrial Fibrillation: Has the Debate Been Settled? Circulation. 2022 Nov 22;146(21):1561-1563. doi: 10.1161/CIRCULATIONAHA.122.060243. Epub 2022 Nov 21. PMID: 36409779.
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6. Packer DL, Piccini JP, Monahan KH, Al-Khalidi HR, Silverstein AP, Noseworthy PA, Poole JE, Bahnson TD, Lee KL, Mark DB; CABANA Investigators. Ablation Versus Drug Therapy for Atrial Fibrillation in Heart Failure: Results From the CABANA Trial. Circulation. 2021 Apr 6;143(14):1377-1390. doi: 10.1161/CIRCULATIONAHA.120.050991. Epub 2021 Feb 8. PMID: 33554614; PMCID: PMC8030730.
7. Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, Noseworthy PA, Rosenberg YD, Jeffries N, Mitchell LB, Flaker GC, Pokushalov E, Romanov A, Bunch TJ, Noelker G, Ardashev A, Revishvili A, Wilber DJ, Cappato R, Kuck KH, Hindricks G, Davies DW, Kowey PR, Naccarelli GV, Reiffel JA, Piccini JP, Silverstein AP, Al-Khalidi HR, Lee KL; CABANA Investigators. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019 Apr 2;321(13):1261-1274. doi: 10.1001/jama.2019.0693. PMID: 30874766; PMCID: PMC6450284.
8. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbüchel H, Hindricks G, Kautzner J, Kuck KH, Mont L, Ng GA, Rekosz J, Schoen N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G; EAST-AFNET 4 Trial Investigators. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 2020 Oct 1;383(14):1305-1316. doi: 10.1056/NEJMoa2019422. Epub 2020 Aug 29. PMID: 32865375.
9. Deshpande R, Al Khadra Y, Al-Tamimi R, Albast N, Labedi M. Atrial fibrillation: Rate control or rhythm control? Cleveland Clinic Journal of Medicine October 2022, 89 (10) 567-571.