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. 2022 Jan;111(1):14-22.
doi: 10.1007/s00392-020-01791-x. Epub 2020 Dec 23.

Antithrombotic therapy with or without clopidogrel after transcatheter aortic valve replacement. A meta-analysis of randomized controlled trials

Costanza Pellegrini  1 , Erion Xhepa  1 , Gjin Ndrepepa  1 , Hector Alvarez-Covarrubias  1   2 , Sebastian Kufner  1 , Anna Lena Lahmann  1   3 , Tobias Rheude  1 , Himanshu Rai  1 , N Patrick Mayr  4 , Heribert Schunkert  1   5 , Adnan Kastrati  1   5 , Michael Joner  1   5 , Salvatore Cassese  6
Affiliations

Antithrombotic therapy with or without clopidogrel after transcatheter aortic valve replacement. A meta-analysis of randomized controlled trials

Costanza Pellegrini et al. Clin Res Cardiol. 2022 Jan.

Abstract

Aims: To investigate the clinical outcomes associated with an antithrombotic therapy with or without clopidogrel after transcatheter aortic valve replacement (TAVR).

Methods and results: This is a study-level meta-analysis including all randomized trials investigating antithrombotic regimens after TAVR. The protocol was registered with PROSPERO (CRD42020191036). We searched electronic scientific databases for eligible studies. The primary outcome was all-cause death. Main secondary outcome was major bleeding. Other outcomes were life-threatening (or disabling) bleeding, myocardial infarction (MI) and stroke. Six eligible trials randomly allocated 3056 TAVR patients to aspirin or oral anticoagulation (OAC) with clopidogrel (n = 1525) versus aspirin and/or OAC without clopidogrel (n = 1531). In the overall estimates, an antithrombotic therapy with clopidogrel versus without displayed a comparable risk of all-cause death [Risk Ratio-RR = 0.83, 95% Confidence intervals-CI (0.57-1.20); P = 0.25] and major bleeding [RR = 1.33, 95% CI (0.61-2.92); P = 0.39]. However, the combination of aspirin or OAC with clopidogrel doubled the risk of major bleeding as compared to aspirin or OAC without clopidogrel [RR = 2.08, 95% CI (1.27-3.42); P = 0.015, P for interaction = 0.021]. Treatment strategies did not differ with respect to the risk of life-threatening bleeding, MI and stroke.

Conclusions: In patients receiving TAVR, a therapeutic strategy of aspirin or OAC with clopidogrel significantly increases the risk of major bleeding without impact on mortality and ischemic outcomes compared to aspirin or OAC without clopidogrel. The performance of different antithrombotic regimens in terms of long-term clinical outcomes and bioprosthesis valve function requires further investigation. Forest plots from pairwise and network meta-analyses associated with an antithrombotic therapy with or without clopidogrel Risk ratio for all outcomes of interest calculated with the pairwise meta-analysis (left side) and for main outcomes calculated with the network meta-analysis (right side) in patients allocated to an antithrombotic therapy with clopidogrel or without. The diamonds indicate the point estimate and the left and the right ends of the lines the [95% CI]. CI: Confidence intervals; OAC; oral anticoagulation.

Keywords: Antithrombotic therapy; Aspirin; Clopidogrel; Meta-analysis; Oral anticoagulation; Transcatheter aortic valve replacement.

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Conflict of interest statement

HS reports honoraria from MSD SHARP and DOHME, AMGEN, Bayer Vital GmbH, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Servier, Brahms, Bristol-Myers Squibb, Medtronic, Sanofi Aventis, Synlab, Pfizer, institutional grant and honoraria from Astra-Zeneca, and travel grants from Vifor outside the submitted work; MJ reports honoraria from Biotronik, Orbus Neich, Boston Scientific, Medtronic, Astra Zeneca, outside the submitted work. SC reports institutional grant and honoraria from SIS Medical, institutional grant and honoraria from Boston Scientific, honoraria from Astra Zeneca, Translumina and Teleflex, outside the submitted work. The other authors declare no potential conflict of interest.

Figures

Fig. 1
Fig. 1
Forest plots for all-cause death and major bleeding associated with an antithrombotic therapy with or without clopidogrel. Risk ratio for all-cause death (Panel a) and major bleeding (Panel b) in patients allocated to an antithrombotic therapy with clopidogrel or without. The diamonds indicate the point estimate and the left and the right ends of the lines the [95% CI]. CI confidence intervals; trial acronyms are reported in Table 1
Fig. 2
Fig. 2
Forest plots for other secondary outcomes associated with an antithrombotic therapy with or without clopidogrel. Risk ratio for life-threatening bleeding (Panel a) and myocardial infarction (Panel b) and stroke (Panel c) in patients allocated to an antithrombotic therapy with clopidogrel or without. The diamonds indicate the point estimate and the left and the right ends of the lines the [95% CI]. CI confidence intervals; trial acronyms are reported in Table 1
See this image and copyright information in PMC

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