Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure: background, aims and design of the RACE 3 study

Abstract

BackgroundRhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF.ObjectiveThe Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion.DesignRACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control.

Impact of Atrial Fibrillation on Exercise Capacity in Heart Failure With Preserved Ejection Fraction

“…A higher resting VO 2 was observed in AF which, as in HFrEF, may signify increased resting energy demands or hypermetabolism corresponding to increased HF severity 31, 32 . These findings support the rationale for aggressive upstream therapy addressing the atrial substrate in HF patients with AF, which is currently under investigation 33 .…”

Risk Factor Management in Atrial Fibrillation

“…45 For this reason, AF management should also no longer solely address single domains such as stroke prevention, symptom relief or preservation of left ventricular function, but increasingly rely on a broader individual and complete approach with timely detection and optimal treatment of risk factors and underlying conditions to improve outcomes and reduce AF burden by targeting the substrate for AF in a more fundamental way. 25,53 As patients with AF have different unfavourable risk factor profiles and many have more than one subclinical or clearly elevated modifiable risk factor, 45,54 interventions aiming at risk factor management -including lifestyle modification and treatment and targeting underlying conditions -need to be patient-centred and tailored to individual needs. Thus, targeted therapy of risk factors and underlying conditions has becomes the fourth pillar of integrated AF.…”

“…or "prevention of atrial remodelling" could improve the outcome of rhythm control therapy and possibly also prognosis in patients with AF. 30,53,156 Several early retrospective and observational studies on upstream therapy with ACE inhibitors, ARBs and statins have produced encouraging results in terms of reduction in AF recurrences, but larger prospective randomised placebo-controlled trials have failed to show any significant reduction in AF recurrences and adverse cardiovascular outcomes, possibly because these studies only addressed a single risk factor. 147,[157][158][159][160][161] More recently, evidence has become available that comprehensive interventions that aim to reduce risk factors and underlying conditions of AF are able to reduce AF recurrence and burden in addition to improving the underlying conditions ( Table 2).…”

European Heart Rhythm Association (EHRA)/European Association of Cardiovascular Prevention and Rehabilitation (EACPR) position paper on how to prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) and Asia Pacific Heart Rhythm Society (APHRS)

“…Aggressive upstream rhythm Control for prevention of Early atrial fibrillation in moderate heart failure (RACE 3) trial is investigating whether the combination of RAAS modulators, statins, and cardiac rehabilitation interventions to promote a better lifestyle including physical activity, weight reduction, and a healthy diet, may reduce progression of AF. 234 …”