Abstract
Background
Severe aortic stenosis (SAS) is a critical condition with high morbidity and mortality if left untreated. Transcatheter aortic valve implantation (TAVI) has emerged as a transformative therapy, especially for patients at high or intermediate surgical risk. However, the optimal post-TAVI antithrombotic therapy remains a subject of debate due to the need to balance thromboembolic prevention with bleeding risks. Current guidelines provide weak recommendations for dual antiplatelet therapy (DAPT) and anticoagulation regimens, reflecting the lack of consensus and robust comparative data.
Objective
This network meta-analysis (NMA) aimed to compare the efficacy and safety of five antithrombotic regimens, including single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), oral anticoagulants (OAC), new oral anticoagulants (NOAC), and OAC combined with SAPT (OAC + SAPT) in patients undergoing TAVI. The primary outcomes were all-cause mortality and major bleeding, while secondary outcomes included cardiovascular mortality, stroke/transient ischemic attack (TIA), and myocardial infarction (MI).
Methods
A comprehensive systematic search was conducted in PubMed, Embase, and Web of Science up to Nov 2024. 11 studies involving 6,547 patients were included in this NMA. Outcomes were analyzed using a frequentist NMA approach, and treatments were ranked using surface under the cumulative ranking curve (SUCRA) probabilities.
Results
SAPT was the most effective regimen in reducing all-cause mortality (OR 0.57, 95% CI 0.38–0.85; SUCRA 85.0%) and major bleeding events (SUCRA 93.8%). DAPT ranked highest for reducing cardiovascular mortality (SUCRA 68.7%), while OAC + SAPT showed superiority in preventing stroke/TIA (SUCRA 76.1%). SAPT also ranked highest in reducing MI risk (SUCRA 69.2%). In contrast, NOAC and OAC were associated with higher bleeding risks and limited mortality benefits, positioning them as less favorable options in this analysis.
Conclusions
This study provides compelling evidence supporting SAPT as the preferred antithrombotic regimen for most TAVI patients, given its consistent performance in reducing all-cause mortality, MI, and major bleeding events. DAPT may be a suitable alternative for patients at elevated risk of cardiovascular death, while OAC + SAPT offers potential benefits in reducing stroke/TIA risks but requires careful consideration due to its higher bleeding risk. NOAC and OAC alone were associated with increased bleeding complications and limited efficacy, highlighting the need for cautious application in specific patient subgroups.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12872-025-04862-x.
Keywords: Transcatheter aortic valve implantation, Antithrombotic therapy, Network meta-analysis, Bleeding risk, Mortality
Introduction
As defined by the American College of Cardiology/American Heart Association (ACC/AHA), severe aortic stenosis (SAS) is defined as a condition in which the aortic valve can be accelerated at a peak velocity of 4.0 m per second, the mean gradient of the valve is greater than or equal to 40 millimeters per second, or the area is less than or equal to one centimeter squared [1, 2]. A person with SAS, if untreated, may die within a short period of time [3]. It is estimated that overall mortality is 8% (3-month) and 36% (3-year) [1]. Currently, a variety of interventions are presently accessible for SAS, encompassing balloon valvuloplasty, surgical replacement of the aortic valve, and transcatheter valve implantation (TAVI) [4–6]. Particularly, among intermediate and high surgical risk patients, TAVI is becoming an increasingly popular therapeutic option [6]. However, the optimal antithrombotic therapy for patients after TAVI is unknown. Fortunately, the latest guidelines recommend dual antiplatelet therapy (DAPT) for 6 months after TAVI and anticoagulation with a vitamin K antagonist (VKA) for 3 months to prevent valve thrombosis, but both are class IIb recommendations [7]. To the best of our knowledge, there is no clear consensus regarding the most favorable antithrombotic regimens for patients post-TAVI.
Many studies have explored the safety and efficacy of antithrombotic regimens after TAVI. An antiplatelet therapy trial that included patients undergoing TAVI who did not receive oral anticoagulation as indications, found that patients taking aspirin were significantly less likely to develop bleeding or thromboembolic events at one year compared to those taking aspirin plus clopidogrel [8]. In contrast, ATLANTIS trial results indicate that Apixaban is not superior to the standard of care after TAVI, regardless of the indication [9]. Thus, the efficacy of antithrombotic regimens remains unclear at present, and only a few studies have assessed the effectiveness of oral anticoagulants (OAC, this article refers specifically to traditional oral anticoagulants such as low-molecular heparin, warfarin, and other vitamin K antagonists.
New oral anticoagulant (NOAC), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), and oral anticoagulant (OAC) + SAPT (OAC + SAPT) are important considerations in the management of patients with TAVI [7]. The most appropriate antithrombotic therapy for this high-risk group should therefore be determined to be one that compares the risks and benefits of antithrombotic therapy following TAVI procedures, based on the risks and benefits of each type of antithrombotic therapy. As a result of a network meta-analysis, we were able to compare different antithrombotic strategies to gain valuable insight into a significant and common clinical problem. Therefore, the objective of this investigation was to analyze various antithrombotic protocols in patients undergoing TAVI, aiming to prevent myocardial infarction (MI), stroke, or transient ischemic attack (TIA), major, disabling, or life-threatening bleeding events, as well as death from cardiovascular causes, or death from any cause that could occur after treatment.
Materials and methods
Literature review
During the construction phase of the library and continuing until November 2, 2024, a thorough examination of the PubMed, Embase, and Web of Science databases has been conducted. Detailed information about the search strategy is provided in the supplementary materials 1. This meta-analysis meets the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements and has been registered on PROSPERO (CRD42025630937).
Inclusion and exclusion criteria
For studies to be eligible, the following criteria had to be met: (I) Research objects: The following five interventions are recommended for patients over 18 years old who have had post-TAVI antithrombosis following the AHA/ACC guidelines for 2020 and the ESC/EACTS guidelines for 2021. (II) Interventions: Each study included at least one of the five antithrombotic regimens listed above. We excluded studies that met one or more of the following criteria: (I) A review, letter, case report, comment, or editorial was the type of publication; (II) An in vitro test or an animal test is the typical study design in the literature; (III) The article contains the remaining drugs in addition to the five antithrombotic regimens mentioned above; (IV) Unavailability or insufficiency of data. Language restriction to English.
Data collection and outcomes
Two reviewers, Jingxian Han and Keyao Liu, conducted an independent data extraction using a standardized form. The reviewers resolved disagreements through consensus, if necessary, and with the assistance of a third reviewer (Professor Yan). The primary outcome was death data from any cause (in the event that any type of death occurs after treatment, it may be due to any of the above causes). Secondary outcomes included MI, stroke, or TIA, major, disabling, or life-threatening bleeding events, as well as death from cardiovascular causes.
Risk of bias assessment and quality assessment
The evaluation of each article was a collaborative effort between two reviewers, Jingxian Han and Keyao Liu, who independently assessed the studies for compliance with the review criteria and addressed any disagreements by consulting a third reviewer, professor Yan. Using the cochrane risk of bias assessment tool, the same independent reviewers assessed the following seven domains for risk of bias: random sequence generation, allocation concealment, blinding of participants, blinding of personnel, blinding of outcome assessment, incomplete data for outcome assessment, selective reporting, and other biases. Based on the factors mentioned above, we have classified the risk of bias as low, high, or unclear. The assessment’s quality was determined by a third reviewer who agreed to resolve any disagreements about it.
Statistical analysis
To perform frequentist effects NMA we used the mvmeta command in STATA 16.0 (Texas, USA: StataCorp, 2020). Each outcome was presented using a network graph in which we compared all the treatments based on that outcome. The evidence diagram illustrates that each node signifies a distinct intervention measure, while the connecting lines denote various head-to-head comparisons among those interventions. The dichotomous variables were analyzed as risk ratios (OR) with 95% confidence intervals (CI). The I2 statistic was used to assess statistical heterogeneity in each comparison. The magnitude of the analysis made it impossible to consider dose differences. The random-effect model was applied if I2 exceeded 50%, otherwise the fixed-effect model was used [10]. The network graphs we used for each outcome presented all treatment comparisons. Based on the results of the NMA, we calculated the rank probability for every intervention and comparison and established the treatment hierarchy using the surface under the cumulative ranking curve (SUCRA). The greater the SUCRA probability, the more likely it is that the preferred regimen will be chosen. Considering the relative risk and 95% CI for each comparison is also critical when interpreting ranking results [11]. The publication bias for primary outcomes and adverse events in the health care system was assessed through a visual inspection of funnel plots produced by STATA16.0.
Results
Study characteristics and risks of bias of the included study
Each study participating in the analysis of each outcome’s risk of bias has been evaluated in supplementary materials 3. Among 967 studies identified, 11 trials (6,547 participants) [8, 9, 12–20] met our eligibility criteria (Fig. 1). Of the included 11 studies, 11 studies [8, 9, 12–20] involved death from any cause, 7 studies [8, 9, 12, 15, 16, 19, 20] provided death from cardiovascular causes, 11 studies [8, 9, 12–20] related to stroke or TIA, 10 studies [8, 9, 12, 14–20] covered MI and 11 studies [8, 9, 12–20] provided major, disabling, or life-threatening bleeding events. In Table 1, we summarize the baseline characteristics of the studies included. The network plot is included as Fig. 2.
Fig. 1.
Study flow diagram
Table 1.
Trial characteristics
| Study | n | Mean age (y) | Female sex (%) | Diabetes mellitus (%) | Previous MI (%) | Previous stroke ± TIA (%) | AF (%) | CKD (%) | Intervention | Control | Follow-up (months) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Brouwer et al., | 665 | 81 | 49 | 25 | 9 | 5 | NR | NR | ASA 80–100 mg daily + clopidogrel 75 mg daily ×3 months, then ASA 80–100 mg daily | ASA 80–100 mg daily | 12 |
| Ussia et al., | 79 | 81 | 54 | 27 | 14 | 8 | 13 | 14 | ASA 100 mg daily + clopidogrel 75 mg daily ×3 months, then ASA 100 mg daily | ASA 100 mg daily | 6 |
| Collet et al., | 1500 | 82 | 53 | 29 | 12 | 11 | 27 | NR | Apixaban 5 mg twice daily ± single antiplatelet therapy | VKA ± single antiplatelet therapy or ASA ± clopidogrel daily | 12 |
| Dangas et al., | 1644 | 81 | 49 | 29 | NR | 5 | NR | NR | ASA 75–100 mg daily + rivaroxaban 10 mg daily ×3 months, then rivaroxaban 10 mg daily | ASA 75–100 mg daily + clopidogrel 75 mg daily ×3 months, then ASA 75–100 mg daily | 17 |
| De Backer et al., | 231 | 80.1 | 83 | 183 | NR | 214 | NR | NR | Rivaroxaban plus aspirin (10 mg once daily (75 to 100 mg) once daily for 3 months, followed by monotherapy with rivaroxaban (10 mg) once daily |
aspirin (75 to 100 mg) and clopidogrel (75 mg) once daily for 3 months, followed by monotherapy with aspirin |
3 |
| Hui et al., | 144 | 84 | 79 | 44 | 20 | 22 | 52 | NR | NOACs and warfarin | aspirin and clopidogrel | 6 |
| Nijenhuis et al., | 313 | 80 | 45 | 28 | 11 | 10 | 95 | NR | OAC daily + clopidogrel 75 mg daily ×3 months, then OAC daily | OAC daily | 12 |
| Park et al., | 229 | 80 | 58 | 31 | 1 | 7 | NR | 37 | Edoxaban 60 mg daily | ASA 100 mg daily + clopidogrel 75 mg daily | 6 |
| Rodés-Cabau et al., | 222 | 79 | 42 | 35 | 21 | NR | NR | 63 | ASA 80–100 mg daily + clopidogrel 75 mg daily | ASA 80–100 mg daily | 3 |
| Rogers et al., | 94 | 73 | 30 | 34 | 2 | 1 | NR | 2 | Warfarin (INR target 2.5) daily + ASA 75–100 mg daily | ASA 75–100 mg daily | 1 |
| Van Mieghem et al., | 1426 | 82 | 48 | 37 | 14 | 17 | 1 | NR | Edoxaban 60 mg daily | VKA (INR target 2–3) daily | 18 |
AF, atrial fibrillation; ASA, acetylsalicylic acid; CKD, chronic kidney disease; NR, not reported; MI, myocardial infarction; NOAC, novel oral anticoagulant; NR, not reported; TIA, transient ischaemic attack; VKA, vitamin K antagonist
Fig. 2.
The network diagrams of all-cause death
Death from any cause
As shown in Fig. 3, SAPT was more effective than NOAC (OR 0.57, 95% CI 0.38–0.85), OAC (OR 0.55, 95% CI 0.34–0.91). No treatment has shown significant advantages over the others during DAPT and OAC + SAPT. The effects of all drugs were ranked with SUCRA probabilities (eFigure 1 in the Supplementary materials 2), SAPT had the highest probability as a treatment option to reduce death in patients after TAVI from any cause (SUCRA 85.0%), followed by DAPT (SUCRA 82.8%), OAC + SAPT (SUCRA 43.8%), NOAC (SUCRA 20.8%) and OAC ranked last (SUCRA 17.6%).
Fig. 3.
Pooled odd ratios for death from any cause
Death from cardiovascular cause
This study examined the effect of these drugs on cardiovascular death in 7 studies [8, 9, 12, 15, 16, 19, 20]. As shown in Fig. 4, compared with SAPT, DAPT, OAC, NOAC and OAC + SAPT showed no significant advantages in reducing cardiovascular death. For all that, as shown in eFigure 2 in the Supplementary materials 2, DAPT reduced the possibility of cardiovascular death at the top-ranking position (SUCRA 68.7%), followed by SAPT (SUCRA 61.1%), OAC (SUCRA 56.4%), OAC + SAPT (SUCRA 39.4%), NOAC (SUCRA 24.4%).
Fig. 4.
Pooled odd ratios for death from cardiovascular cause
Stroke/TIA
11 studies [8, 9, 12–20] reported stroke or TIA. Despite the 5 antithrombotic regimens not having a significant advantage in reducing the events of stroke or TIA, as shown in Figs. 5. OAC + SAPT reduced the likelihood of Stroke or TIA events in the first rank (SUCRA 76.1%), with SAPT (SUCRA 59.8%) in second, NOAC (SUCRA 39.6%) in third, and DAPT (SUCRA 38.4%) and OAC (SUCRA 36.0%) in last (eFigure 3 in the Supplementary materials 2).
Fig. 5.
Pooled odd ratios for stroke/TIA
Myocardial infarction
Ten studies [8, 9, 12, 14–20] investigated the events of myocardial infarction. There was no significant reduction in MI events as shown in Fig. 6. Our results suggested that (eFigure 4 in the Supplementary materials 2), regarding prevention of MI, SAPT (SUCRA 69.2%) was most effective, followed by OAC (SUCRA 66.6%), OAC + SAPT (SUCRA 55.6%), NOAC (SUCRA 34.4%), DAPT (SUCRA 24.2%).
Fig. 6.
Pooled odd ratios for myocardial infarction
Major, disabling, or life-threatening bleeding events
In 11 trials [8, 9, 12–20], data on major, disabling, or life-threatening bleeding events were available. The results of Fig. 7 show a statistically significant reduction in major, disabling, or life-threatening bleeding events following SAPT compared with DAPT and NOAC (OR 0.58, 95% CI 0.36–0.92 and OR 0.55, 95% CI 0.32–0.94). OAC had the advantage of preventing major, disabling, or life-threatening bleeding events in comparison to NOAC (OR 0.72, 95% CI 0.53–0.97). In terms of reducing major, disabling, or life-threatening bleeding events, SAPT was the superior (eFigure 5 in the Supplementary materials 2, SUCRA 93.8%), followed by OAC (SUCRA 72.4%) and DAPT (SUCRA 34.7%), NOAC (SUCRA 27.9%), and OAC + SAPT was rated the most dreadful (SUCRA 21.1%).
Fig. 7.
Pooled odd ratios for major, disabling, or life-threatening bleeding events
Publication bias
We employed funnel plots to evaluate publication bias for each arm of the comparison [21]. In the event that each arm had more than 10 trials, further statistical analysis of funnel plot asymmetry would be conducted. It was not possible to discern substantial asymmetry in the Begg funnel plot, and there was no indication of a publication bias in the primary outcome based on visual inspection (Supplementary materials 2).
Discussion
The findings of this study suggest that SAPT is the most effective regimen for reducing death from any cause and MI in patients after TAVI, followed by DAPT, OAC + SAPT, NOAC, and OAC alone. In addition, compared with SAPT, DAPT, OAC, NOAC and OAC + SAPT showed no significant advantages in reducing cardiovascular death and the occurrence of stroke/TIA. However, DAPT reduced the possibility of cardiovascular death at the top-ranking position (SUCRA 68.7%) and OAC + SAPT reduced the likelihood of stroke/TIA events in the first rank (SUCRA 76.1%). These findings indicate that SAPT may be a preferred treatment option in this population, aligning with previous studies that have shown the benefits of SAPT in reducing mortality in TAVI patients [22–24]. Regarding the potential risk of major, disabling, or life-threatening bleeding events, SAPT may be superior, followed by OAC, DAPT, NOAC, and OAC + SAPT. Taken together, this study provides compelling evidence supporting SAPT as the preferred antithrombotic regimen for most TAVI patients, given its consistent performance in reducing all-cause mortality, MI, and major bleeding events.
Pharmacologically, SAPT prevents thrombosis by inhibiting platelet aggregation. For example, aspirin irreversibly inhibits platelet cyclooxygenase to reduce the generation of thromboxane A2, and clopidogrel blocks ADP receptors to inhibit platelet aggregation [25]. Moreover, it demonstrates high safety, a reduced bleeding risk compared to DAPT and OAC, and fewer adverse effects on the gastrointestinal tract and other organs in clinical settings. It is significantly effective, can reduce all-cause mortality and major bleeding events, prevent MI, and is consistent with the results of the ATLANTIS trial. DAPT usually refers to the combination of aspirin and clopidogrel etc., which prevents thrombosis by inhibiting platelet aggregation through a dual mechanism [26]. In terms of clinical significance, it may be effective in preventing cardiovascular death and is suitable for high-risk patients, which is consistent with the results of the PIONEER AF-PCI trial. But the adverse event is that the bleeding risk is relatively high, and it is necessary to evaluate the bleeding and thrombosis risks of patients and individualized treatment.
Nevertheless, OAC mainly inhibits thrombin generation to prevent thrombosis, including warfarin and NOAC [27]. In terms of clinical significance, OAC may be the most effective in preventing stroke or TIA, which is consistent with the results of the RE-LY trial [28]. The combination of OAC + SAPT may also be effective in preventing stroke or TIA by combining the two mechanisms. But the adverse event is that the bleeding risk of OAC is high, and it is necessary to monitor the coagulation function regularly and adjust the dose [29]. The bleeding risk of OAC + SAPT is also high, and individualized risk assessment is required. NOAC prevents thrombosis by directly inhibiting coagulation factor Xa or thrombin and it has a lower bleeding risk compared to warfarin, does not require regular monitoring of the coagulation function, and is convenient to use. But the adverse event is that the benefit in this network meta-analysis is relatively small, which may be related to the number and sample size of the included studies.
SAPT, DAPT, OAC, OAC + SAPT, and NOAC may be all effective antithrombotic treatment options, but each has its own advantages and limitations (supplementary materials 4). Choosing the optimal antithrombotic regimen requires thorough evaluation of the patient’s condition, including factors such as bleeding risk, thrombotic risk, medical history, comorbidities, and treatment objectives. SAPT can be considered as the preferred treatment option for reducing mortality and major bleeding events, particularly for patients with a higher bleeding risk. DAPT can be chosen as a strategy for preventing cardiovascular death, especially in high-risk patients. OAC plus SAPT can be used to reduce the risk of stroke or TIA, while OAC can be used for preventing MI. However, when choosing an antithrombotic regimen, it is crucial to consider the individual patient’s condition and treatment objectives and to make individualized treatment decisions [7].
No antithrombotic regimen demonstrated significant superiority over the others regarding cardiovascular mortality. However, DAPT ranked highest in reducing the possibility of cardiovascular death (SUCRA 68.7%), followed by SAPT, OAC, OAC + SAPT, and NOAC. These findings suggest that DAPT may be a favorable option for preventing cardiovascular mortality in TAVI patients [30]. Regarding the prevention of stroke or TIA, OAC + SAPT ranked first (SUCRA 76.1%), followed by SAPT, NOAC, DAPT, and OAC. These results indicate that OAC + SAPT may be the most effective regimen in reducing the risk of stroke or TIA in patients after TAVI. However, it is important to note that the differences between regimens were not statistically significant, highlighting the need for further research in this area. The analysis also evaluated the occurrence of MI events and found that SAPT was the most effective regimen (SUCRA 69.2%), followed by OAC, OAC + SAPT, NOAC, and DAPT. These findings suggest that SAPT may offer the best protection against MI in TAVI patients. Importantly, SAPT exhibited a statistically significant decrease in major bleeding events compared to DAPT and NOAC. OAC also showed an advantage over NOAC in preventing major bleeding events. SAPT was ranked as the superior regimen (SUCRA 93.8%) for reducing major bleeding events, followed by OAC and DAPT. OAC + SAPT was associated with the highest risk of major bleeding events. These findings highlight the importance of considering bleeding risk when selecting an antithrombotic regimen for TAVI patients [31].
Although these findings have important clinical implications for managing antithrombotic therapy in TAVI patients, further research is needed to validate them and provide more robust evidence regarding the optimal antithrombotic regimen after TAVI. Therefore, in the future, randomized controlled trials with larger sample sizes and longer follow-up durations are warranted to evaluate the long-term effectiveness and safety of different treatment strategies. Additionally, studies investigating the impact of patient-specific factors on treatment outcomes would help guide personalized decision-making in this population.
It is essential to acknowledge some limitations that may influence the interpretation of the findings presented in this network meta-analysis. First, the included studies varied in their design, sample size, and follow-up duration, which may have introduced heterogeneity and potential bias. Second, the analysis focused on short-term outcomes, and long-term effects of the antithrombotic regimens could not be evaluated. Third, individualized treatment decisions should consider patient-specific factors, such as age, bleeding risk, history of thromboembolic events, and comorbidities. However, the analysis did not consider individual patient characteristics and comorbidities, which could influence the effectiveness and safety of different antithrombotic regimens. Fourth, this meta-analysis was limited to published studies, which may introduce publication bias. Unpublished or ongoing studies were not included in the analysis, potentially affecting the overall findings. Finally, the analysis did not assess the impact of specific antithrombotic regimens on valve thrombosis, which is an important consideration in TAVI patients. Despite these limitations, the findings of this meta-analysis provide valuable insights into the comparative effectiveness of different antithrombotic regimens in TAVI patients. The results suggest that SAPT may be the most effective regimen for reducing all-cause mortality, while DAPT may be beneficial for preventing cardiovascular death.
In conclusion, this network meta-analysis suggests that different antithrombotic regimens have varying effectiveness and safety profiles in patients undergoing transcatheter TAVI. SAPT appears to be the most effective in reducing all-cause mortality, while DAPT may be beneficial for preventing cardiovascular death. OAC plus SAPT may be effective in reducing the risk of stroke or TIA, and SAPT alone may offer advantages in preventing myocardial infarction. SAPT also demonstrated a significant reduction in major bleeding events. These findings provide valuable insights for clinicians in selecting the most appropriate antithrombotic regimen for TAVI patients, emphasizing the importance of individualized treatment decision. The results also underscore the need for further randomized controlled trials with longer follow-up durations to validate these findings, explore long-term outcomes, and guide clinical practice.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
The authors have no acknowledgments to report.
Author contributions
Jx.H: Data curation, writing-original and methodology; Ky.L.: Methodology and investigation; Yx.L.: Methodology; D.H.: Software and methodology; Pc.L.: Conceptualization; Nj.Z.: Formal analysis and funding; Sq.H.: Writing-reviewing, editing and funding; Xl.Y.: Supervision and funding.
Funding
The research of our article was funded by Yunlong Lake Laboratory of Deep Earth Science and Engineering Project (104024005, Xianliang Yan), Construction Project of High Level Hospital of Jiangsu Province (GSPJS202419,GSPJS202425 Xianliang Yan, Ningjun Zhao), Xuzhou Medical Leading Talent Training Project (XWRCHT20210026, Xianliang Yan);5G + Healthcare Application Pilot Project of Ministry of Industry and Information Technology and National Health Commission, (2021, Xianliang Yan), Natural Science Foundation of Jiangsu Province (BK20231162, Xianliang Yan), Key Project of Jiangsu Provincial Health Commission (K2023020, Shuqun Hu), Major Project of Biotherapy Research Special Project of Xuzhou Health Research Institute (XJZ2023002, Shuqun Hu). General Project of Shanxi Provincial Natural Science Basic Research Program (S2023-JC-YB-2309, Pengchong Liang, Shuqun Hu), Jiangsu Province College Student Innovation and Entre preneurship Training Program (202210313006Z, Yuxin Li).
Data availability
All data generated or analysed during this study are included in this published article.
Declarations
Ethics approval and consent to participate
This is a systematic review and meta-analysis, ethics approval and consent to participate are not applicable.
Consent for publication
Not applicable. The manuscript does not include the participant’s identification image or other personal or clinical details.
Competing interests
The authors declare no competing interests.
Clinical trial number
not applicable.
Generative AI disclosure
This article was written by the author independently, without using any AI tools or software to generate, edit or modify the content.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jingxian Han, Keyao Liu and Yuxin Li contributed equally to this work.
Contributor Information
Ningjun Zhao, Email: njxydoc@163.com.
Shuqun Hu, Email: hushuqun88@xzhmu.edu.cn.
Xianliang Yan, Email: docyxl@163.com.
References
- 1.Benfari G, Essayagh B, Michelena HI, et al. Severe aortic stenosis: secular trends of incidence and outcomes[J]. Eur Heart J. 2024;45(21):1877–86. [DOI] [PubMed] [Google Scholar]
- 2.Taniguchi T, Morimoto T, Shiomi H, et al. Initial surgical versus conservative strategies in patients with asymptomatic severe aortic stenosis[J]. J Am Coll Cardiol. 2015;66(25):2827–38. [DOI] [PubMed] [Google Scholar]
- 3.Strange G, Stewart S, Playford D, et al. Risk for mortality with increasingly severe aortic stenosis: an international cohort study[J]. J Am Soc Echocardiogr. 2023;36(1):60–8. e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Samaja GA. Balloon aortic valvuloplasty in the transcatheter aortic valve implantation era[J]. Heart Int. 2023;17(1):13–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Mehaffey JH, Jagadeesan V, Kawsara M, et al. Transcatheter versus surgical aortic valve replacement in bicuspid aortic valves[J]. Ann Thorac Surg. 2024. [DOI] [PubMed]
- 6.Kedhi E, Hermanides RS, Dambrink JE et al. TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and complex or multivessel coronary disease (TCW): an international, multicenter, prospective, open-label, non-inferiority, randomized controlled trial[J]. Lancet. 2025;404(10471):2593-2602. [DOI] [PubMed]
- 7.Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines[J]. Circulation. 2021;143(5):e35–71. [DOI] [PubMed] [Google Scholar]
- 8.Brouwer J, Nijenhuis VJ, Delewi R, et al. Aspirin with or without clopidogrel after transcatheter aortic-valve implantation[J]. N Engl J Med. 2020;383(15):1447–57. [DOI] [PubMed] [Google Scholar]
- 9.Collet JP, Van Belle E, Thiele H, et al. Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial[J]. Eur Heart J. 2022;43(29):2783–97. [DOI] [PubMed] [Google Scholar]
- 10.Tian J, Zhang J, Ding L, et al. Association between sleep duration and low bone mineral density and osteoporosis: a systematic review and meta-analysis[J]. Calcif Tissue Int. 2024;116(1):3. [DOI] [PubMed] [Google Scholar]
- 11.Yang R, Hu C, Zhuo Y, et al. Comparative efficacy of Chinese tonic medicines for treating sepsis or septic shock: a systematic review and Bayesian network meta-analysis of randomized controlled trials[J]. Phytomedicine. 2024;136:156295. [DOI] [PubMed] [Google Scholar]
- 12.Dangas GD, Tijssen JGP, Wöhrle J, et al. A controlled trial of rivaroxaban after transcatheter aortic-valve replacement[J]. N Engl J Med. 2020;382(2):120–9. [DOI] [PubMed] [Google Scholar]
- 13.De Backer O, Dangas GD, Jilaihawi H, et al. Reduced leaflet motion after transcatheter aortic-valve replacement[J]. N Engl J Med. 2020;382(2):130–9. [DOI] [PubMed] [Google Scholar]
- 14.Hui S, Gooley R, Rashid HN, et al. Transcatheter aortic valve replacement and atrial fibrillation: impact of antithrombotic strategy on clinical outcomes[J]. Heart Lung Circ. 2019;28(5):771–6. [DOI] [PubMed] [Google Scholar]
- 15.Nijenhuis VJ, Brouwer J, Delewi R, et al. Anticoagulation with or without clopidogrel after transcatheter aortic-valve implantation[J]. N Engl J Med. 2020;382(18):1696–707. [DOI] [PubMed] [Google Scholar]
- 16.Park DW, Ahn JM, Kang DY, et al. Edoxaban versus dual antiplatelet therapy for leaflet thrombosis and cerebral thromboembolism after TAVR: the ADAPT-TAVR randomized clinical trial[J]. Circulation. 2022;146(6):466–79. [DOI] [PubMed] [Google Scholar]
- 17.Rodés-Cabau J, Masson JB, Welsh RC, et al. Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following transcatheter aortic valve replacement with a balloon-expandable valve: the ARTE (Aspirin versus aspirin + clopidogrel following transcatheter aortic valve implantation) randomized clinical trial[J]. JACC Cardiovasc Interv. 2017;10(13):1357–65. [DOI] [PubMed] [Google Scholar]
- 18.Rogers T, Shults C, Torguson R, et al. Randomized trial of aspirin versus warfarin after transcatheter aortic valve replacement in low-risk patients[J]. Circ Cardiovasc Interv. 2021;14(1):e009983. [DOI] [PubMed] [Google Scholar]
- 19.Ussia GP, Scarabelli M, Mulè M, et al. Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation[J]. Am J Cardiol. 2011;108(12):1772–6. [DOI] [PubMed] [Google Scholar]
- 20.Van Mieghem NM, Unverdorben M, Hengstenberg C, et al. Edoxaban versus vitamin K antagonist for atrial fibrillation after TAVR[J]. N Engl J Med. 2021;385(23):2150–60. [DOI] [PubMed] [Google Scholar]
- 21.Liu XX, Ma YQ, Kong LY, et al. Unveiling the therapeutic role of Dachaihu decoction in acute cholecystitis: a comprehensive systematic review and meta-analysis of its efficacy and safety[J]. Front Pharmacol. 2024;15:1497072. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Bansal A, Kumar A, Jain V, et al. Benefit of single antiplatelet therapy over dual antiplatelet therapy after transcatheter aortic valve implantation[J]. Am J Cardiol. 2021;141:163–4. [DOI] [PubMed] [Google Scholar]
- 23.Gandhi S, Schwalm JD, Velianou JL, et al. Comparison of dual-antiplatelet therapy to mono-antiplatelet therapy after transcatheter aortic valve implantation: systematic review and meta-analysis[J]. Can J Cardiol. 2015;31(6):775–84. [DOI] [PubMed] [Google Scholar]
- 24.Ullah W, Zghouzi M, Ahmad B, et al. Meta-analysis comparing the safety and efficacy of single vs dual antiplatelet therapy in post transcatheter aortic valve implantation patients[J]. Am J Cardiol. 2021;145:111–8. [DOI] [PubMed] [Google Scholar]
- 25.Schrör K. Aspirin and platelets: the antiplatelet action of aspirin and its role in thrombosis treatment and prophylaxis[J]. Semin Thromb Hemost. 1997;23(4):349–56. [DOI] [PubMed] [Google Scholar]
- 26.Zhou YH, Wei X, Lu J, et al. Effects of combined aspirin and clopidogrel therapy on cardiovascular outcomes: a systematic review and meta-analysis[J]. PLoS ONE. 2012;7(2):e31642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Wadhera RK, Russell CE, Piazza G. Cardiology patient page. Warfarin versus novel oral anticoagulants: how to choose? [J]. Circulation. 2014;130(22):e191–3. [DOI] [PubMed] [Google Scholar]
- 28.Connolly SJ, Pogue J, Eikelboom J, et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range[J]. Circulation. 2008;118(20):2029–37. [DOI] [PubMed] [Google Scholar]
- 29.Potpara TS, Lip GY. Oral anticoagulant therapy in atrial fibrillation patients at high stroke and bleeding risk[J]. Prog Cardiovasc Dis. 2015;58(2):177–94. [DOI] [PubMed] [Google Scholar]
- 30.Ch IA, Latif F, Usmani A, et al. Dual antiplatelet therapy after elective coronary artery bypass graft and its impact on clinical Outcomes[J]. Ann Thorac Surg Short Rep. 2024. [DOI] [PMC free article] [PubMed]
- 31.Khan F, Tritschler T, Kimpton M, et al. Long-term risk for major bleeding during extended oral anticoagulant therapy for first unprovoked venous thromboembolism: a systematic review and meta-analysis[J]. Ann Intern Med. 2021;174(10):1420–9. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All data generated or analysed during this study are included in this published article.