Author + information
- Julia Seeger, MD∗ (, )
- Sinisa Markovic, MD,
- Mirjam Kessler, MD,
- Wolfgang Rottbauer, MD and
- Jochen Wöhrle, MD
- ↵∗Department of Internal Medicine II–Cardiology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Although the MitraClip (Abbott Vascular, Santa Clara, California) for percutaneous repair of severe mitral regurgitation has been used in more than 25,000 patients, antiplatelet or anticoagulation treatment has not been universally defined. Optimal treatment after MitraClip implantation in patients with maintained sinus rhythm is unclear. On the one hand, the use of antiplatelet therapy (APT) only after MitraClip implantation seems to be sufficient to avoid the generation of thrombotic mass at the clip itself. On the other hand, the large device and handling of the guide in the left atrium may lead to endothelial lesions that could trigger generation of thrombotic masses with subsequent embolic events. In patients with endothelial damage in the left atrium after ablation of atrial fibrillation, the use of oral anticoagulation is the standard of care to avoid embolic events (1).
We evaluated in a prospective observational registry the safety and efficacy of apixaban plus aspirin compared with APT alone in patients with MitraClip implantation and maintained sinus rhythm.
MitraClip implantation was performed as described elsewhere (2). Percutaneous repair was decided by the heart team. Treatment strategy was consecutive with APT alone followed by anticoagulation with apixaban plus aspirin. Outcome was assessed according to the Mitral Valve Academic Research Consortium-2 criteria. Written informed consent was obtained from all patients (NCT03104660). All patients were on aspirin before the procedure. Apixaban 2.5 mg twice daily was started 24 h after MitraClip implantation in patients with sinus rhythm (Figure 1A). Patients were followed up after 30 days and 12 months.
The combined endpoint at 30 days was a composite of all-cause mortality, all stroke, and rehospitalization for congestive heart failure or myocardial infarction. A landmark analysis after 30 days was performed with the use of Kaplan-Meier estimates and were compared with the log-rank test and Cox proportional regression hazard ratio. A multivariate analysis was performed to identify independent predictors for the combined endpoint. A p value <0.05 was considered to be statistically significant.
A total of 254 patients were enrolled. Apixaban plus aspirin was administered in 53.5% (n = 136) for 4 weeks post-procedure followed by APT alone. APT only after MitraClip implantation was administered in 46.5% (n = 118) of patients. Of the 118 patients on APT, 72.1% (n = 85) were on single APT and 27.9% (n = 33) were on dual APT with clopidogrel after previous percutaneous coronary intervention. Baseline characteristic including sex, New York Heart Association (NYHA) functional class, platelet count, cardiovascular risk factors, history of cardiac interventions, CHA2DS2-VASc and HAS-BLED scores, and procedural data were similar between groups. However, patients in the apixaban group were significantly younger (p = 0.02), and mean NYHA functional class was significantly lower (p < 0.01). After 30 days, the stroke rate was lower in patients on apixaban plus aspirin (0% vs. 0.9%; p = 0.28), and the combined endpoint was significantly lower in patients on aspirin plus apixaban compared with patients on APT only (1.4% vs. 7.6%; p = 0.02). Within 30 days of follow-up, 4 patients in the antiplatelet group died, of which 3 were cardiac deaths and 1 noncardiac death related to aspiration-induced hypoxia. In the apixaban group, 1 noncardiac death occurred within the first 30 days.
There was no major bleeding in both groups within 30 days of follow-up (Figure 1B). In multivariate analysis, the antithrombotic regimen with APT or apixaban was the only independent predictor (p = 0.011) for the combined endpoint at 30 days (odds ratio [OR]: 0.18; 95% confidence interval [CI]: 0.038 to 0.867), but not sex (p = 0.54; OR: 0.85; 95% CI: 0.242 to 3.02), age (p = 0.31; OR; 0.239; 95% CI: 0.502 to 11.41), NYHA functional class (p = 0.87; OR: 0.951: 95% CI: 0.242 to 3.741), STS score (p = 0.052; OR: 0.21; 95% CI: 0.0001 to 1.02), left ventricular function (p = 0.34, OR: 0.478; 95% CI: 0.123 to 1.857) or etiology of mitral regurgitation (p = 0.90, OR: 0.690; 95% CI: 0.2035 to 2.341). In the landmark analysis after 30 days, the combined endpoint was statistically not significantly different for patients initially on apixaban plus aspirin compared with patients with APT only (Figure 1B).
Currently, patients after MitraClip implantation without indication for oral anticoagulation are empirically recommended dual APT for the first 30 days followed by lifelong aspirin (3). However, this regimen has not been evaluated in a randomized controlled trial. Triple therapy increased risk of bleeding and is not recommended. Case studies, however, showed thrombus formation in the left atrium despite dual APT (4). We were able to demonstrate in a prospective observational registry a significantly lower combined endpoint at 30 days for sinus rhythm patients treated with apixaban plus aspirin compared with APT only. For stroke prevention, non–vitamin k oral anticoagulant agents (NOACs) have been approved in nonvalvular atrial fibrillation patients (5). Currently, there is no evidence for the use of a NOAC in sinus rhythm patients after MitraClip. Large controlled randomized trials are missing. In the landmark analysis after discontinuation of apixaban after 30 days, there was no difference in the combined endpoint in both groups. The unknown risk of device thrombosis and left atrial thrombus formation within the first 30 days might be adequately addressed with oral anticoagulation. Hence, patients undergoing MitraClip implantation might benefit from post-interventional anticoagulation with a NOAC, not only if in atrial fibrillation. This is a first observational finding. The results have to be considered hypothesis generating. Number of patients is limited, and event rates are low. Larger randomized controlled trials are needed to confirm this hypothesis.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
- Arbelo E.,
- Brugada J.,
- Blomström-Lundqvist C.,
- et al.
- Seeger J.,
- Müller P.,
- Gonska B.,
- et al.