JAMA cardiology最新文献

Importance: Sex is associated with the clinical presentation, outcomes, and response to treatment in patients with heart failure (HF). However, little is known about the safety and efficacy of treatment with finerenone according to sex.

Objective: To estimate the efficacy and safety of finerenone compared with placebo in both women and men.

Design, setting, and participants: Prespecified analyses were conducted in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF). The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction (LVEF) of 40% or greater randomized between September 2020 and January 2023.

Intervention: Finerenone (titrated to 20 mg or 40 mg) or placebo.

Main outcomes and measures: The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events (unplanned HF hospitalizations or urgent HF visits).

Results: A total of 6001 patients were randomized in FINEARTS-HF, of whom 2732 were women (45.5%), with a mean (SD) age of 73.6 (9.1) years. Women had higher rates of any obesity, higher LVEF (54.6 [7.6%] vs 50.9 [7.6] for men), lower mean (SD) estimated glomerular filtration rate than men (59.7 [19.1] vs 64.1 [20.0] for men; P<.001) , worse New York Heart Association functional class, and lower Kansas City Cardiomyopathy Questionnaire-Total Symptom Scores (KCCQ-TSS) (mean [SD] 62.3 [24.0] vs 71.0 [23.1]). The incident rate of the primary outcome was slightly lower in women (15.7; 95% CI, 14.3-17.3) than in men (16.8; 95% CI, 15.4-18.3) per 100 person-years. Compared with placebo, finerenone reduced the risk of the primary end point similarly in women and men: rate ratio 0.78 (95% CI, 0.65-0.95) in women and 0.88 (95% CI, 0.74-1.04) in men (P = .41 for interaction). Consistent effects were observed for the components of the primary outcome and all-cause mortality. The mean increase (improvement) in KCCQ-TSS from baseline to 12 months was greater with finerenone, regardless of sex (P = .73 for interaction). Finerenone had similar tolerability in women and men.

Conclusions and relevance: In FINEARTS-HF, finerenone reduced the risk of the primary end point similarly in women and men with heart failure with mildly reduced or preserved ejection fraction. Finerenone had similar tolerability in women and men.

Trial registration: ClinicalTrials.gov Identifier: NCT04435626.

Importance: Treatment with finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), improved outcomes in patients with heart failure with mildly reduced or preserved ejection fraction in FINEARTS-HF, but was associated with increased levels of serum potassium in follow-up.

Objective: To investigate the frequency and predictors of serum potassium level greater than 5.5 mmol/L and less than 3.5 mmol/L and examine the treatment effect associated with finerenone, relative to placebo, on clinical outcomes based on postrandomization potassium levels.

Design, setting, and participants: Secondary analysis of the FINEARTS-HF multicenter, randomized clinical trial, performed between September 14, 2020, and January 10, 2023, with a median follow-up of 32 months (final date of follow-up: June 14, 2024). Patients with heart failure and left ventricular ejection fraction greater than or equal to 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides were included.

Intervention: Participants received finerenone or placebo.

Main outcomes and measures: The primary outcome was a composite of total worsening heart failure events or cardiovascular death.

Results: A total of 6001 participants were included (3003 randomized to receive finerenone and 2998 randomized to receive placebo). The increase in serum potassium was greater in the finerenone group than the placebo group at 1 month (median [IQR] difference, 0.19 [0.17-0.21] mmol/L) and 3 months (median [IQR] difference, 0.23 [0.21-0.25] mmol/L), which persisted for the remainder of trial follow-up. Finerenone increased the risks of potassium level increasing to greater than 5.5 mmol/L (hazard ratio [HR], 2.16 [95% CI, 1.83-2.56]; P < .001) and decreased the risks for potassium level decreasing to less than 3.5 mmol/L (HR, 0.46 [95% CI, 0.38-0.56]; P < .001). Both low (< 3.5 mmol/L; HR, 2.49 [95% CI, 1.8-3.43]) and high (>5.5 mmol/L; HR, 1.64 [95% CI, 1.04-2.58]) potassium levels were associated with higher subsequent risks of the primary outcome in both treatment groups. Nevertheless, the risk of the primary outcome was generally lower in patients treated with finerenone compared with placebo, even in those whose potassium level increased to greater than 5.5 mmol/L.

Conclusions and relevance: In patients with heart failure with mildly reduced or preserved ejection fraction, finerenone resulted in more frequent hyperkalemia and less frequent hypokalemia. However, with protocol-directed surveillance and dose adjustment, clinical benefit associated with finerenone relative to placebo was maintained even in those whose potassium level increased to greater than 5.5 mmol/L.

Trial registration: ClinicalTrials.gov Identifier: NCT04435626.

Importance: Efficient approaches to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) are still needed.

Objective: To investigate whether partial cardiac denervation, achieved by cutting off the ligament of Marshall (LOM) and resecting the fat pad along the Waterston groove, can reduce the risk of POAF following CABG.

Design, setting and participants: This single-center, randomized clinical trial enrolled adult patients scheduled for isolated CABG in China. Enrollment was from August 15, 2022, to December 13, 2023; follow-up visits were 30 days after discharge.

Interventions: Participants were randomized into the intervention group (CABG plus partial cardiac denervation) and the control group (CABG only) in a 1:1 pattern. All participants were continuously monitored for the incidence of POAF until day 6 after the operation.

Main outcome and measures: The primary end point was the incidence of POAF in 6 days, defined as a supraventricular arrhythmia lasting for more than 30 seconds.

Results: The trial enrolled 430 patients (79 [18.4%] female; mean [SD] age, 61.9 [7.8] years). Compared with the control group, the 6-day incidence of POAF was significantly lower in the intervention group (18.1% vs 31.6%; P = .001; risk ratio, 0.57 [95% CI, 0.41-0.81]). To further support these results, a sensitivity analysis performed with Kaplan-Meier survival curves also showed a significant reduction in the occurrence of POAF in the intervention group (hazard ratio, 0.53 [95% CI, 0.36-0.79]; P = .002). Safety assessments showed no difference between the 2 groups, while postoperative medical cost was reduced in the intervention group.

Conclusions and relevance: This randomized clinical trial found that partial cardiac denervation was an effective procedure to reduce the occurrence of POAF after isolated CABG without additional postoperative complications. These results suggest that partial cardiac denervation may be a good option for cardiac surgeons to consider for preventing POAF after CABG.

Trial registration: ClinicalTrials.gov Identifier: NCT05009914.