Objectives
The French left atrial appendage (LAA) closure registry (FLAAC) aimed to assess the safety and efficacy of LAA closure in daily practice.
Background
LAA closure has emerged as an ...alternative for preventing thromboembolic events (TE) in patients with non‐valvular atrial fibrillation (NVAF). Clinical data in this field remains limited and few investigator‐initiated, real‐world registries have been reported.
Methods
This nationwide, prospective study was performed in 36 French centers. The primary endpoint was the TE rate after successful LAA closure.
Results
The FLAAC registry included 816 patients with a mean age of 75.5 ± 0.3 years, mean follow‐up of 16.0 ± 0.3 months, high TE (CHA2DS2‐VASc score: 4.6 ± 0.1) and bleeding risks (HAS‐BLED score: 3.2 ± 0.05) and common contraindications to long‐term anticoagulation (95.7%). Procedure or device‐related serious adverse events occurred in 49 (6.0%) patients. The annual rate of ischemic stroke/systemic embolism was 3.3% (2.4–4.6). This suggests a relative 57% reduction compared to the risk of stroke in historical NVAF populations without antithrombotic therapy. By multivariate analysis, history of TE was the only factor associated with stroke/systemic embolism during follow‐up (HR, 3.3 1.58–6.89, p = 0.001). The annual mortality rate was 10.2% (8.4–12.3). Most of the deaths were due to comorbidities or underlying cardiovascular diseases and unrelated to the device or to TE.
Conclusions
Our study suggests that LAA closure can be an option in patients with NVAF. Long‐term follow‐up mortality was high, mostly due to comorbidities and underlying cardiovascular diseases, highlighting the importance of multidisciplinary management after LAA closure.
Registration
NCT02252861.
Metformin, the classic anti-diabetic drug, improves motor symptoms in the DMSXL mouse model of myotonic dystrophy type 1. Bassez et al. now report a significant increase in patients' mobility ...following treatment with the maximal tolerated dose of metformin as compared to placebo in a double-blind randomized phase II clinical trial.
Abstract
Metformin, the well-known anti-diabetic drug, has been shown recently to improve the grip test performance of the DMSXL mouse model of myotonic dystrophy type 1. The drug may have positively affected muscle function via several molecular mechanisms, on RNA splicing, autophagia, insulin sensitivity or glycogen synthesis. Myotonic dystrophy remains essentially an unmet medical need. Since metformin benefits from a good toxicity profile, we investigated its potential for improving mobility in patients. Forty ambulatory adult patients were recruited consecutively at the neuromuscular reference centre of Henri-Mondor Hospital. Participants and investigators were all blinded to treatment until the end of the trial. Oral metformin or placebo was provided three times daily, with a dose-escalation period over 4 weeks up to 3 g/day, followed by 48 weeks at maximum dose. The primary outcome was the change in the distance walked during the 6-minute walk test, from baseline to the end of the study. Concomitant changes in muscle strength and effect on myotonia, gait variables, biological parameters and quality of life were explored. Patients randomized into two arms eventually revealed similar results in all physical measures and in the mean 6-minute walk test at baseline. For the 23/40 patients who fully completed the 1-year study, differences between the groups were statistically significant, with the treated group (n = 9) gaining a distance of 32.9 ± 32.7 m, while the placebo group (n = 14) gained 3.7 ± 32.4 m (P < 0.05). This improvement in mobility was associated with an increase in total mechanical power (P = 0.01), due to a concomitant increase in the cranial and antero-posterior directions suggesting an effect of the treatment on gait. Subanalysis revealed positive effects of metformin treatment on the 6-minute walk test at the first intermediate evaluation (after 16 weeks of treatment), quantitatively similar to those recorded at 1 year. In contrast, except for the expected limited weight loss associated to metformin treatment, there was no change in any of the other secondary endpoints, including myotonia and muscle strength. Patients in the treated group had a higher incidence of mild-to-moderate adverse effects, mostly gastrointestinal dysfunctions that required symptomatic treatment. Although results were statistically significant only for the per protocol population of patients and not in the intent-to-treat analysis, metformin at the maximal tolerated dose provided a promising effect on the mobility and gait abilities of myotonic patients. These encouraging results obtained in a small-scale monocentric phase II study call for replication in a well-powered multicentre phase III trial.
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