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For patients with early atrial fibrillation (Afib) and cardiovascular (CV) conditions, early rhythm-control therapy was tied to a lower risk of CV outcomes than usual care, a researcher reported.

The EAST-AFNET 4 trial was stopped after a median of 5.1 years in favor of efficacy when it was determined that the strategy of early-rhythm control was superior, with the rate of primary endpoint events at 3.9 per 100 person-years in the early-control group versus 5.0 per 100 person-years in the usual care group (hazard ratio 0.79, 96% CI 0.66-0.94), for a statistically significant difference (P=0.005), according to Paulus Kirchhof, MD, of the University Heart and Vascular Center at the Universitatsklinikum Hamburg-Eppendorf in Germany.

The mean number of nights spent in the hospital did not differ significantly between the groups at 5.8 days per year versus 5.1 days per year (P=0.23), according to the trial results online in the .

"We think that these results will inform the future use of rhythm control therapy in atrial fibrillation patients, and they suggest that early rhythm control therapy should be offered to all patients with early atrial fibrillation at risk of cardiovascular complications," Kirchhof said during a press conference at the European Society of Cardiology virtual meeting.

For the trial, 1,395 patients were assigned to the strategy of early-rhythm control therapy and 1,394 patients to usual care strategies at 135 sites in 11 European countries. The average age of the patients was 70 and women made up about 46%. About 73% of patients in both groups had asymptomatic Afib.

"Beneficial effects of early rhythm control therapy was consistent across all components of the composite endpoint," Kirchhof said. "Numerically there were fewer cardiovascular events, fewer strokes, fewer hospitalizations for heart failure [HF], fewer hospitalizations for acute coronary syndrome [ACS]."

Kirchhof and colleagues also reported that the following for the early-rhythm control group versus the usual care group:

• Death from CV causes: 67/6,915 person-years (rate of 1%) versus 94/6,988 person-years (rate of 1.3%)
• Strokes: 40/6,813 person-years (0.6%) versus 62/6,856 person-years (0.9%)
• Hospitalizations with worsening HF: 139/6,620 person-years (2.1%) versus 169/6,558 person-years (2.6%)
• Hospitalizations with ACS: 53/6,762 person-years (0.8%) versus 65/6,816 person-years (1.0%)

"These results should and will change practice," commented Jonathan P. Piccini, MD, of the Duke University Medical Center in Durham, North Carolina. "The EAST trial will be a landmark in atrial fibrillation science."

"We have known for a long time that atrial fibrillation is a progressive disease that leads to multiple adverse cardiovascular outcomes, including stroke, heart failure, cognitive impairment, and reduced quality of life, " Piccini, a spokesperson for the American Heart Association who was not involved in the study, told 乌鸦传媒.

"Rhythm control seeks to restore and maintain sinus rhythm in order to improve symptoms and quality of life," he explained. "While we have long hypothesized that maintaining sinus rhythm would improve hard cardiovascular outcomes, prior trials that have compared rhythm control with rate control were neutral."

The results of EAST change that, Piccini emphasized. "The results show that when we intervene early to maintain sinus rhythm in patients with atrial fibrillation and cardiovascular disorders, we see lower rates of cardiovascular outcomes. Moreover, EAST shows no difference in the overall safety outcome after a median of 5 years of follow-up per patient. Thus, the trial demonstrates that early rhythm control is superior to usual care," he said.

The authors reported that serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% assigned to usual care.

Kirchhof noted that "in the last few years, we have made remarkable progress in the management of patients with atrial fibrillation, the most common cardiac arrhythmia. Anticoagulation now prevents most ischemic strokes and many patients are asymptomatic. Nonetheless, 5% of unselected patients with atrial fibrillation develop cardiovascular death, stroke, or are hospitalized with acute heart failure or acute coronary syndrome per year."

"There are two reasons why we thought that intervening early would make a difference compared with the current delayed approach," Kirchhof explained. "There is good data to show that complications are common during the first year after diagnosis of atrial fibrillation. So there is a window of opportunity to prevent complications."

"Secondly...once you are in atrial fibrillation for a few months, the atria suffers severe damage, some of which may be irreversible, so it becomes more difficult to restore and maintain sinus rhythm," he said.

His group also found that symptoms and left ventricular function at 2 years did not differ significantly between the groups.

"There were a few differences between EAST and prior studies of rate rhythm control trials. One is that we employed not only rhythm-control drugs but also atrial fibrillation ablation, a powerful tool to maintain sinus rhythm, particularly when combined with antiarrhythmic drugs," he said.

"Secondly we tested patients with early diagnosed atrial fibrillation," Kirchhof said. "Almost 40% of patients had their first episode of atrial fibrillation when they were randomized and the median time between the first diagnosis of atrial fibrillation and randomization was 36 days in the trial."

Study limitations included the comparison of two treatment strategies that required an open trial design. Also, "the trial was not primarily designed to assess the safety and effectiveness of specific components of early-rhythm control," the authors noted.

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