RACE 3 long-term results show fading benefit of targeted therapies in AF and HF

In the RACE 3 trial, patients with early persistent atrial fibrillation (AF) and heart failure (HF) received either conventional plus targeted therapies or conventional therapies alone. While results were promising at 1 year, results from the 5-year extension study did not show superior efficacy of combined treatment [1].

Targeted therapies aim to modify the atrial substrate and have a favourable effect on risk factors and diseases underlying AF. Previously, the 1-year results of the RACE 3 trial (NCT00877643) suggested that targeted therapies in addition to conventional therapies improves sinus rhythm maintenance in patients with early persistent AF and mild-to-moderate early HF [2]. Prof. Michiel Rienstra (University Medical Center Groningen, the Netherlands) presented the 5-year results from the RACE 3 extension study [1].

The multicentre, randomised RACE 3 trial aimed to evaluate whether the targeted therapy of underlying conditions could benefit sinus rhythm maintenance by reducing cardiovascular risk [2]. Participants with early AF and mild-to-moderate HF were randomly assigned to conventional therapies (n=109) or conventional plus targeted therapies (i.e. mineralocorticoid receptor antagonists, statins, ACE-inhibitors and/or angiotensin-receptor blockers, or cardiac rehabilitation; n=107). After 3 weeks, all patients were electrocardioverted and received rhythm control and HF therapy according to guidelines. Patients in the targeted arm were followed-up every 3 months for 5 years, patients in the conventional arm every 3 months for 1 year and then once yearly. Patient characteristics were similar in both groups; the mean age was 64 and 65 years, respectively, and 21% were women. The primary endpoint was sinus rhythm during 7-day Holter monitoring at 1 year. The presented outcomes were the long-term effects after 5 years of follow-up.

At 1 year, sinus rhythm was achieved by 75% of participants receiving targeted therapy versus 63% of participants receiving conventional therapy only (OR 1.177; 95% CI 1.02-3.05; P=0.042), showing superior efficacy of the targeted therapy [2]. At 5 years, targeted therapy led to sinus rhythm in 46% of participants assigned to intervention versus 39% of participants on conventional therapy (OR 1.297; 95% CI 0.76-2.23; P=0.346); thus, no longer showing a significant difference in efficacy.

After 5 years, the rate of cardiovascular morbidity or mortality was similar between the treatment arms (log-rank P=0.353). Changes in the underlying conditions were statistically significant in systolic blood pressure, total cholesterol, and LDL-cholesterol, with more favourable outcomes for the targeted treatment group. Prof. Rienstra concluded that these long-term outcomes showed that targeted therapies on top of conventional studies did not improve maintenance of sinus rhythm in patients with persistent AF and HF at 5-year follow-up. However, the study may have limited power due to the small number of participants (n=109).

1. 
   
   1. Rienstra M. Targeted therapy of underlying conditions in patients with persistent atrial fibrillation and mild to moderate stable heart failure: long-term outcome of the RACE 3 Trial. EHRA 2021 Congress, 23-25 April.
   2. Rienstra M, et al. Eur Heart J 2018:39(32):2987-2996.

 

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Posted on 16 June 202116 June 2021