No indication for oral anticoagulation after TAVI: SAPT outperforms DAPT and DOAC-based regimens
Antithrombotic Therapy and Cardiovascular Outcomes After Transcatheter Aortic Valve Implantation in Patients Without Indications for Chronic Oral Anticoagulation: A systematic review and network meta-analysis of randomized controlled trialsLiterature - Guedeney P, Roule V, Mesnier J, et al. - Eur Heart J Cardiovasc Pharmacother. 2023 Jan 14;pvad003. doi: 10.1093/ehjcvp/pvad003
Introduction and methods
For patients undergoing transcatheter aortic valve implantation (TAVI) who have no baseline indication for chronic oral anticoagulation, current European guidelines now recommend lifelong single antiplatelet therapy (SAPT) [1,2]. However, these guidelines did not include the latest results from RCTs comparing direct oral anticoagulants (DOACs) with antiplatelet therapy [3,4].
Aim of the study
The study aim was to compare the safety and efficacy of several antithrombotic regimens following TAVI in patients with no indication for chronic oral anticoagulation.
The authors conducted a systematic review of the literature (according to the PRISMA guidelines) and network meta-analysis of RCTs that evaluated any antithrombotic regimen in patients undergoing TAVI for symptomatic severe aortic valve stenosis who did not have an indication for chronic oral anticoagulation (publication up to April 2022).
In total, 7 studies were included, which comprised 4006 patients, of whom 650 (16.2%) received SAPT, 1893 (47.3%) were taking dual antiplatelet therapy (DAPT), and 1463 (36.5%) were on DOACs (of whom 526 (13.1%) on apixaban, 111 (2.8%) on edoxaban, and 826 (20.6%) on low-dose rivaroxaban plus 3-month SAPT). The patient population was deemed to be old and frail and have an intermediate-to-high risk profile. Mean weighted follow-up time was 12.9 months.
The primary efficacy endpoint was all-cause death, and the primary safety endpoint was life-threatening, disabling, or major bleeding as defined in each study. Other endpoints of interest were CV and non-CV death, MI, stroke, systemic embolism, and grade 3 or 4 reduced leaflet motion (RLM) as reported in each study. Endpoints were collected at the longest available time of follow-up, according to the intention-to-treat principle.
- Patients treated with DAPT showed a reduction of all-cause death compared with those receiving a combination treatment of low-dose rivaroxaban plus 3-month SAPT (RR : 0.60; 95%CI: 0.41–0.88) and also a reduction of non-CV death (RR: 0.39; 95%CI: 0.20–0.77).
- There was no significant difference in all-cause death between the SAPT and DAPT groups (RR: 1.02; 95%CI: 0.67–1.58), nor between the SAPT and DOAC only groups (RR: 0.60; 95%CI: 0.32–1.14) or the DAPT and DOAC only groups (RR: 0.59; 95%CI: 0.34–1.02).
- Additionally, no significant difference was observed in CV or non-CV death between the SAPT and DAPT groups, nor between the SAPT or DAPT group and the DOAC only group.
- Overall, no heterogeneity across data sources was observed (I²=0%; P=0.95), neither within study designs (P=0.77) nor between study designs (P=0.99). Review of P scores indicated that DAPT was ranked highest for risk of all-cause death (P score=0.84), CV death (P score=0.82), and non-CV death (P score=0.83).
- In the SAPT group, the risk of life-threatening, disabling, or major bleeding was reduced compared with the DAPT group (RR: 0.45; 95%CI: 0.29–0.70), the DOAC only group (RR: 0.45; 95%CI: 0.25–0.79), and low-dose rivaroxaban plus 3-month SAPT group (RR: 0.30; 95%CI: 0.16–0.57).
- Similarly, the risk of major bleeding was reduced for SAPT versus DAPT (RR: 0.38; 95%CI: 0.22–0.68), SAPT versus DOAC only (RR: 0.41; 95%CI: 0.20–0.82), SAPT versus low-dose rivaroxaban plus 3-month SAPT (RR: 0.19; 95%CI: 0.08–0.45), and DAPT versus low-dose rivaroxaban plus 3-month SAPT (RR: 0.50; 95%CI: 0.27–0.93).
- There was no difference in the incidence of life-threatening or disabling bleeding between any of the treatment groups.
- No heterogeneity was observed for the outcome life threatening, disabling, or major bleeding (I²=0%; P=0.82) or major bleeding (I²=0%; P=0.73), nor within study designs (P=0.57 and P=0.81, respectively) or between study designs (P=0.73 and P=0.40, respectively). SAPT was ranked highest for all safety outcome risks (all P scores=0.99).
- Between the different treatment regimens, no significant differences were observed in the risk of MI, stroke, or systemic embolism.
- The risk of grade 3 or 4 RLM did not differ between the SAPT and DAPT groups (RR: 1.58; 95%CI: 0.69–3.57). However, when SAPT was compared with the other treatment regimens, this risk was increased compared with DOAC only (RR: 6.81; 95%CI: 2.23–20.81) and low-dose rivaroxaban plus 3-month SAPT (RR: 8.27; 95%CI: 1.52–45.0).
- No heterogeneity was observed among the comparisons of the different secondary outcomes, neither within nor between study designs . DOAC only treatment was ranked highest for MI risk (P score=0.76), SAPT was ranked highest for stroke risk (P score=0.71), and DAPT (P score=0.64) was ranked highest for systemic embolism risk.
This systematic review and network meta-analysis of 7 RCTs evaluating patients undergoing TAVI for symptomatic severe aortic valve stenosis who did not have an indication for chronic oral anticoagulation showed that the use of SAPT was associated with a 55% reduction of bleeding risk compared with DAPT or DOAC only treatment. There was no difference in the occurrence of all-cause death between SAPT and the other antithrombotic regimens.
According to the authors, this “superior benefit-risk ratio” of SAPT compared with DAPT and various DOAC regimens confirms the current European guideline recommendations on lifelong SAPT after TAVI for patients with no indication for chronic oral anticoagulation.