Antithrombotic therapy after transcatheter mitral valve repair and replacement: a systematic review of outcomes and safety

Abstract

Background:Transcatheter mitral valve intervention, including repair (e.g., edge-to-edge repair) and replacement, is now a cornerstone of treatment for severe mitral regurgitation (MR) in high-risk patients, providing a less invasive alternative to surgical treatment. The purpose of this systematic review is to assess the efficacy and safety of different antithrombotic strategies to prevent thromboembolic events and bleeding complications after transcatheter mitral valve repair (TMVR).

Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search on PubMed, Embase, Web of Science, Scopus, and Cochrane Library was conducted from January 2015 to January 2025. Eligible studies included adult patients who underwent transcatheter mitral valve intervention (including repair and replacement procedures) and compared different antithrombotic regimens, including direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), and antiplatelet therapies. Two reviewers independently extracted data and assessed quality. The studies were too heterogeneous, so a narrative synthesis was performed.

Results: Fifteen studies involving 20,956 patients were included. DOACs were associated with a lower risk of major bleeding compared to VKAs [hazard ratio (HR): 0.21, p = 0.02, in one large study], with similar rates of stroke. Mortality was lower with DOACs in several analyses (e.g., HR: 0.67). Triple therapy and dual antiplatelet therapy (DAPT) were associated with increased bleeding risk without providing additional thromboembolic protection.

Discussion: DOACs have a safer profile in post-TMVR patients, with reduced bleeding risk and lower mortality compared with VKAs. Triple therapy and DAPT should only be used in high-risk patients with specific indications due to their greater risk of bleeding. Optimizing outcomes requires a tailored approach to antithrombotic therapy, considering patient factors and procedural considerations. Definitive standards may still demand further investigation, such as multicenter randomized controlled trials evaluating antithrombotic treatments after TMVR.

Keywords

transcatheter mitral valve repair / mitral regurgitation / antithrombotic therapy / direct oral anticoagulants

References

[1] Stone GW, Lindenfeld J, Abraham WT, Kar S, Lim DS, Mishell JM, et al.; COAPT Investigators. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018; 379: 2307-18.

[2] Koschutnik M, Dannenberg V, Donà C, Nitsche C, Kammerlander AA, Koschatko S, et al. Transcatheter Versus Surgical Valve Repair in Patients with Severe Mitral Regurgitation. J Pers Med. 2022; 12: 90.

[3] Ramlawi B, Skiles J, Myers D, Ali O, Viens C. Transcatheter mitral repair: MitraClip technique. Ann Cardiothorac Surg. 2018; 7: 824-6.

[4] Feldman T, Kar S, Elmariah S, Smart SC, Trento A, Siegel RJ, et al.; EVEREST II Investigators. Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation: 5-Year Results of EVEREST II. J Am Coll Cardiol. 2015; 66: 2844-54.

[5] Samanidis G, Kanakis M, Perreas K. Outcomes after Transcatheter Mitral Valve Implantation: A Literature Review. J Pers Med. 2022; 12: 2074.

[6] Writing Committee Members; Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2021; 77: e25-197.

[7] Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017; 135: e1159-95.

[8] Maznyczka A, Pilgrim T. Antithrombotic Treatment After Transcatheter Valve Interventions: Current Status and Future Directions. Clin Ther. 2024; 46: 122-33.

[9] Capodanno D, Petronio AS, Prendergast B, Eltchaninoff H, Vahanian A, Modine T, et al. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017; 38: 3382-90.

[10] Potpara TS, Lip GY. Oral anticoagulant therapy in atrial fibrillation patients at high stroke and bleeding risk. Prog Cardiovasc Dis. 2015; 58: 177-94.

[11] Copland M, Walker ID, Tait RC. Oral anticoagulation and hemorrhagic complications in an elderly population with atrial fibrillation. Arch Intern Med. 2001; 161: 2125-8.

[12] Sorajja P, Moat N, Badhwar V, Walters D, Paone G, Bethea B, et al. Initial Feasibility Study of a New Transcatheter Mitral Prosthesis: The First 100 Patients. J Am Coll Cardiol. 2019; 73: 1250-60.

[13] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71.

[14] Mentias A, Saad M, Michael M, Nakhla S, Menon V, Harb S, et al. Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valve Replacement or Repair. J Am Heart Assoc. 2022; 11: e026666.

[15] El Bèze N, Himbert D, Suc G, Brochet E, Ajzenberg N, Cailliau A, et al. Comparison of Direct Oral Anticoagulants vs Vitamin K Antagonists After Transcatheter Mitral Valve Replacement. J Am Coll Cardiol. 2024; 83: 334-46.

[16] Guerrero ME, Bapat VN, Mahoney P, Krishnaswamy A, Eleid MF, Eng MH, et al. Contemporary 1-Year Outcomes of Mitral Valve-in-Ring With Balloon-Expandable Aortic Transcatheter Valves in the U.S. JACC Cardiovasc Interv. 2024; 17: 874-86.

[17] Giustino G, Camaj A, Kapadia SR, Kar S, Abraham WT, Lindenfeld J, et al. Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial. J Am Coll Cardiol. 2022; 80: 1857-68.

[18] Körber MI, Silwedel J, Friedrichs K, Mauri V, Huntgeburth M, Pfister R, et al. Bleeding Complications After Percutaneous Mitral Valve Repair With the MitraClip. Am J Cardiol. 2018; 121: 94-9.

[19] Paukovitsch M, Schepperle N, Pott A, Buckert D, Moritz Schneider L, Keßler M, et al. Impact of bleeding complications after transcatheter mitral valve repair. Int J Cardiol Heart Vasc. 2021; 32: 100707.

[20] Nathan AS, Yang L, Geng Z, Dayoub EJ, Khatana SAM, Fiorilli PN, et al. Oral anticoagulant use in patients with atrial fibrillation and mitral valve repair. Am Heart J. 2021; 232: 1-9.

[21] Li Y, Lei R, Zhou J, Wu K, Shen J, Zhu Z, et al. Innovative use of a self-expanding valve for valve-in-valve transcatheter mitral valve replacement: experience from a four-year single-center study. Front Cardiovasc Med. 2023; 10: 1137663.

[22] Geis NA, Göbbel A, Kreusser MM, Täger T, Katus HA, Frey N, et al. Impact of Percutaneous Mitral Valve Repair Using the MitraClipTM System on Ventricular Arrhythmias and ICD Therapies. Life (Basel). 2022; 12: 344.

[23] Malaisrie SC, Guerrero M, Davidson C, Williams M, de Brito FS Jr, Abizaid A, et al.; PARTNER 3 Mitral Valve-in-Valve Study Investigators. One-Year Outcomes of Transseptal Mitral Valve-in-Valve in Intermediate Surgical Risk Patients. Circ Cardiovasc Interv. 2024; 17: e013782.

[24] Ludwig S, Kalbacher D, Schofer N, Schäfer A, Koell B, Seiffert M, et al. Early results of a real-world series with two transapical transcatheter mitral valve replacement devices. Clin Res Cardiol. 2021; 110: 411-20.

[25] Hohmann C, Ludwig M, Walker J, Iliadis C, Schipper JH, Baldus S, et al. Real-world anticoagulatory treatment after percutaneous mitral valve repair using MitraClip: a retrospective, observational study on 1300 patients. Clin Res Cardiol. 2022; 111: 889-99.

[26] Tichelbäcker T, Körber MI, Mauri V, Iliadis C, Metze C, Adler C, et al. Prevalence of left ventricular thrombus formation after mitral valve edge-to-edge repair. Sci Rep. 2022; 12: 9096.

[27] Schipper JH, Sommer AS, Nies RJ, Metze C, Meertens MM, Wörmann J, et al. Direct Oral Anticoagulants Versus Vitamin K Antagonists After Mitral Valve Transcatheter Edge-to-Edge Repair in Patients With Atrial Fibrillation: A Single-Center Observational Study. J Am Heart Assoc. 2025; 14: e038834.

[28] Alaour B, Ferrari E, Heg D, Tueller D, Pilgrim T, Muller O, et al. Non-Vitamin K Antagonist Versus Vitamin K Antagonist Oral Anticoagulant Agents After Transcatheter Aortic Valve Replacement. JACC Cardiovasc Interv. 2024; 17: 405-18.

[29] Zorman MJ, Vibhishanan J, Dangas K, Castle J, Li KHC, Coronelli M, et al. Valve thrombosis and antithrombotic therapy after bioprosthetic mitral valve replacement: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2025; 11: 251-63.

[30] Sinha T, Riaz A, Rawat A, Phoo CN, Nageye ME, Chaudhari SS, et al. Comparison of Effectiveness and Safety of Dual Antiplatelet Therapy (DAPT) With Clopidogrel and Aspirin Versus Aspirin Monotherapy in Patients With Mild-to-Moderate Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis. Cureus. 2024; 16: e58909.

[31] Pagnesi M, Moroni F, Beneduce A, Giannini F, Colombo A, Weisz G, et al. Thrombotic Risk and Antithrombotic Strategies After Transcatheter Mitral Valve Replacement. JACC Cardiovasc Interv. 2019; 12: 2388-401.

[32] Nijenhuis VJ, Bennaghmouch N, Hassell M, Baan J Jr, van Kuijk JP, Agostoni P, et al. Rationale and design of POPular-TAVI: antiPlatelet therapy fOr Patients undergoing Transcatheter Aortic Valve Implantation. Am Heart J. 2016; 173: 77-85.

[33] Nijenhuis VJ, Ten Berg JM, Hengstenberg C, Lefèvre T, Windecker S, Hildick-Smith D, et al. Usefulness of Clopidogrel Loading in Patients Who Underwent Transcatheter Aortic Valve Implantation (from the BRAVO-3 Randomized Trial). Am J Cardiol. 2019; 123: 1494-500.

[34] Marmagkiolis K, Monlezun DJ, Caballero J, Cilingiroglu M, Brown MN, Ninios V, et al. Prevalence, mortality, cost, and disparities in transcatheter mitral valve repair and replacement in cancer patients: Artificial intelligence and propensity score national 5-year analysis of 7495 procedures. Int J Cardiol. 2024; 408: 132091.

[35] Calabrò P, Gragnano F, Niccoli G, Marcucci R, Zimarino M, Spaccarotella C, et al. Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease. Circulation. 2021; 144: 1323-43.

[36] Andersen OS, Smiseth OA, Dokainish H, Abudiab MM, Schutt RC, Kumar A, et al. Estimating Left Ventricular Filling Pressure by Echocardiography. J Am Coll Cardiol. 2017; 69: 1937-48.

[37] Tomšič A, Zhao C, Schoones JW, Klautz RJM, Palmen M. Oral Anticoagulation Versus Antiplatelet Treatment After Mitral Valve Repair: A Systematic Review and Meta-Analysis. Am J Cardiol. 2024; 210: 58-64.

[38] Pibarot P, Herrmann HC, Wu C, Hahn RT, Otto CM, Abbas AE, et al. Standardized Definitions for Bioprosthetic Valve Dysfunction Following Aortic or Mitral Valve Replacement: JACC State-of-the-Art Review. J Am Coll Cardiol. 2022; 80: 545-61.

[39] Meuris B, Borger MA, Bourguignon T, Siepe M, Grabenwöger M, Laufer G, et al. Durability of bioprosthetic aortic valves in patients under the age of 60 years - rationale and design of the international INDURE registry. J Cardiothorac Surg. 2020; 15: 119.

[40] Blanke P, Leipsic JA, Popma JJ, Yakubov SJ, Deeb GM, Gada H, et al.; Evolut Low Risk LTI Substudy Investigators. Bioprosthetic Aortic Valve Leaflet Thickening in the Evolut Low Risk Sub-Study. J Am Coll Cardiol. 2020; 75: 2430-42.

[41] Roldán V, Marín F, Manzano-Fernández S, Gallego P, Vílchez JA, Valdés M, et al. The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2013; 62: 2199-204.

[42] Zhu W, He W, Guo L, Wang X, Hong K. The HAS-BLED Score for Predicting Major Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis. Clin Cardiol. 2015; 38: 555-61.