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RACE to the top: risk factor-driven upstream therapy results in superior sinus rhythm management

Arrhythmias and Device Therapy

Van-Gelder.jpgRisk-factor upstream therapy has been proven superior to conventional therapy in the maintenance of sinus rhythm in patients with early, short-lasting persistent atrial fibrillation (AF) and/or heart failure (HF) at one year. The revealing results of the RACE 3 trial were presented during yesterday’s Hot Line: Late-Breaking Clinical Trial session by Professor Isabelle C Van Gelder (University of Groningen, Groningen, The Netherlands). 

You all know that maintenance of sinus rhythm improves AF-related symptoms. However, sinus maintenance is cumbersome due to atrial remodelling.” Prof. Van Gelder told the audience. “Risk-factor driven upstream therapy refers to interventions that aim to modify the atrial substrate and, at the same time, have a favourable effect on risk factors and diseases underlying AF.” 

In the prospective, open-label, multicentre trial, patients with early symptomatic persistent AF and/or HF were randomised to either upstream or conventional therapy groups, stratified by percentage of left ventricle ejection fraction. The primary endpoint of the study was the presence of sinus rhythm during at least six-sevenths of accessible time, according to seven-day Holter monitoring at one year. 

One-hundred and nineteen patients were assigned to receive risk-factor upstream therapy and 126 to undergo conventional therapy. Both groups received standard care for AF and HF according to the present guidelines. All participants received cardioversion therapy three weeks after inclusion in the study. The mean age was 65 years and 80% of participants were men. Risk factor-driven therapies were initiated in the upstream group: mineralocorticoid receptor antagonist, statins, ACE-inhibitors and/or angiotensin-receptor blockers as well as cardiac rehabilitation. All medical therapy was titrated to the highest tolerated dosage except for statins, which were given at the recommended dosage. Target blood pressure was set at <120/80mmHg. The upstream group took part in a cardiac rehabilitation programme, consisting of supervised exercise—which began immediately following inclusion and before cardioversion—and tailored counselling every six weeks to stimulate sports performance. Patients took part in supervised physical activity two to three times per week for between nine and 11 weeks. Sports were encouraged for at least half an hour, five times per week, as well as medication compliance. In addition, participants were limited to <7.5g sodium intake per day, calorie intake reduction if they had a body mass index (BMI) ≥27kg/m2, and fluid restriction depending on the severity of heart failure. At one year, 75% of the upstream group achieved sinus rhythm, compared with 63% of the conventional group, resulting in an odds ratio of 1.765 with a lower 95% confidence interval of 1.115 and a p-value of 0.021. 

Looking at secondary endpoints, Prof. Van Gelder said, “Blood pressure reduction was significantly larger in the upstream group, and the same was true for N-terminal pro b-type natriuretic peptide.” Both groups saw a similar increase in ejection fraction, while low density lipid reduction was significantly higher in the upstream group. No changes or differences between the groups were observed in BMI and left atrial volume. Prof. Van Gelder said, “Therapy including treatment of risk factors and lifestyle is effective and feasible to improve the maintenance of sinus rhythm in patients with early persistent atrial fibrillation and heart failure.” The RACE 3 results were favourable to the impact of upstream therapy on the reduction of risk factors, instead of its effect on atrial remodelling, she explained, concluding that “RACE 3 may contribute to the shift in focus on risk factor modification to improve outcomes in AF patients.” 

“In the last few years, we have devoted a lo t of effort to the symptoms and consequences of AF,” discussant reviewer, Professor Josep Brugada Terradellas, Hospital Clinic Barcelona, Barcelona, Spain, stated. “But clearly we have failed in controlling the epidemic of AF in our society.” Casting a critical eye towards the study, Prof. Brugada Terradellas noted that RACE 3 was limited by its failure to account for factors known to be associated with AF, including alcohol intake and sleep apnoea. He stated his surprise that even the control group achieved 63% sinus rhythm, and—noting the “dual epidemic” of obesity and AF—he expressed regret that BMI results were not improved in the upstream group. In spite of these limitations, he praised the study, telling the audience that it “opens the door” to future research which may demonstrate that aggressive therapy can reduce the number of patients with AF. “If we are more aggressive,” he concluded, “we might find a preventative therapy and maybe, in the future, we will reduce the burden of AF.”

Resources of the presentation: Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure, the RACE 3 study

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