Efficacy and safety of direct oral anticoagulants versus vitamin K antagonists for left ventricular thrombus: an updated systematic review and meta-analysis

Aim    To perform a systematic review and meta-analysis of efficacy and safety of direct oral anticoagulants (DOAC) as compared to vitamin K antagonists (VKA) in the treatment of left ventricular (LV) thrombosis.
Material and methods    A search was performed in PubMed and Google Scholar for studies that compared DOAC and VKA in the treatment of LV thrombosis with respect of thromboembolic events, hemorrhagic complications, and thrombus resolution. The effect was evaluated with the odds ratio (OR) that was computed using a fixed effects model.
Results    For these systematic review and meta-analysis, 19 studies were selected, including 2 randomized and 17 cohort studies. The articles included into these systematic review and meta-analysis, were published from 2018 through 2021. In total, 2970 patients (mean age, 58.8 years; 1879 (61.2 %) men) with LV thrombus were included into the meta-analysis. Mean follow-up duration was 17.9 months. The meta-analysis showed no significant difference between DOAC and VKA in the incidence of the study outcomes: thromboembolic events (OR, 0.86; 95 % CI: 0.67–1.10; р=0.22), hemorrhagic complications (OR, 0.77; 95 % CI: 0.55–1.07; р=0.12), thrombus resolution (OR, 0.96; 95 % CI: 0.76–1.22; р=0.77). In a subgroup analysis, rivaroxaban compared to VKA significantly (79%) reduced the risk of thromboembolic complications (OR, 0.21; 95 % CI: 0.05–0.83; р=0.03) with no significant differences in hemorrhagic events (OR, 0.60; 95 % CI: 0.21–1.71; р=0.34) or thrombus resolution (OR, 1.44; 95 % CI: 0.83–1.31; р=0.20). The apixaban treatment group had significantly more (4.88 times) cases of thrombus resolution than the VKA treatment group (OR, 4.88; 95 % CI: 1.37–17.30; р=0.01); for apixaban, data on hemorrhagic and thromboembolic complications were not available.
Conclusions    The therapeutic efficacy and side effects of the DOAC treatment for LV thrombosis were similar to those of VKA with respect of thromboembolic events, hemorrhage, and thrombus resolution.

1. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–236. DOI: 10.1161/STR.0000000000000024

2. Solheim S, Seljeflot I, Lunde K, Bjørnerheim R, Aakhus S, Forfang K et al. Frequency of Left Ventricular Thrombus in Patients With Anterior Wall Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention and Dual Antiplatelet Therapy. The American Journal of Cardiology. 2010;106(9):1197–200. DOI: 10.1016/j.amjcard.2010.06.043

3. Mao TF, Bajwa A, Muskula P, Coggins TR, Kennedy K, Magalski A et al. Incidence of Left Ventricular Thrombus in Patients With Acute ST-Segment Elevation Myocardial Infarction Treated with Percutaneous Coronary Intervention. The American Journal of Cardiology. 2018;121(1):27–31. DOI: 10.1016/j.amjcard.2017.09.010

4. Gianstefani S, Douiri A, Delithanasis I, Rogers T, Sen A, Kalra S et al. Incidence and Predictors of Early Left Ventricular Thrombus After ST-Elevation Myocardial Infarction in the Contemporary Era of Primary Percutaneous Coronary Intervention. The American Journal of Cardiology. 2014;113(7):1111–6. DOI: 10.1016/j.amjcard.2013.12.015

5. Robinson AA, Jain A, Gentry M, McNamara RL. Left ventricular thrombi after STEMI in the primary PCI era: A systematic review and meta-analysis. International Journal of Cardiology. 2016;221:554–9. DOI: 10.1016/j.ijcard.2016.07.069

6. O’Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-e425. DOI: 10.1161/CIR.0b013e3182742cf6

7. Mekaj A, Mekaj Y, Duci S, Miftari E. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Therapeutics and Clinical Risk Management. 2015;11:967–77. DOI: 10.2147/TCRM.S84210

8. Cochran JM, Jia X, Kaczmarek J, Staggers KA, Rifai MA, Hamzeh IR et al. Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombus: A Retrospective, Multicenter Study and Meta-Analysis of Existing Data. Journal of Cardiovascular Pharmacology and Therapeutics. 2021;26(2):173–8. DOI: 10.1177/1074248420967644

9. Guddeti RR, Anwar M, Walters RW, Apala D, Pajjuru V, Kousa O et al. Treatment of Left Ventricular Thrombus With Direct Oral Anticoagulants: A Retrospective Observational Study. The American Journal of Medicine. 2020;133(12):1488–91. DOI: 10.1016/j.amjmed.2020.05.025

10. Iqbal H, Straw S, Craven TP, Stirling K, Wheatcroft SB, Witte KK. Direct oral anticoagulants compared to vitamin K antagonist for the management of left ventricular thrombus. ESC Heart Failure. 2020;7(5):2032–41. DOI: 10.1002/ehf2.12718

11. Robinson AA, Trankle CR, Eubanks G, Schumann C, Thompson P, Wallace RL et al. Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi. JAMA Cardiology. 2020;5(6):685–92. DOI: 10.1001/jamacardio.2020.0652

12. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Medicine. 2009;6(7):e1000097. DOI: 10.1371/journal.pmed.1000097

13. Sereda AP, Andrianova MA. Study Design Guidelines. Traumatology and Orthopedics of Russia. 2019;25(3):165–84. DOI: 10.21823/2311-2905-2019-25-3-165-184

14. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. DOI: 10.1136/bmj.l4898

15. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. European Journal of Epidemiology. 2010;25(9):603–5. DOI: 10.1007/s10654-010-9491-z

16. Cochrane Collaboration. Review Manager (RevMan). Version 5.4.1. Av. at: https://training.cochrane.org/system/files/uploads/protected_file/RevMan5.4_user_guide.pdf. 2020.

17. Abdelnabi M, Saleh Y, Fareed A, Nossikof A, Wang L, Morsi M et al. Comparative Study of Oral Anticoagulation in Left Ventricular Thrombi (No-LVT Trial). Journal of the American College of Cardiology. 2021;77(12):1590–2. DOI: 10.1016/j.jacc.2021.01.049

18. Albabtain MA, Alhebaishi Y, Al-Yafi O, Kheirallah H, Othman A, Alghosoon H et al. Rivaroxaban versus warfarin for the management of left ventricle thrombus. The Egyptian Heart Journal. 2021;73(1):41. DOI: 10.1186/s43044-021-00164-7

19. Alcalai R, Butnaru A, Moravsky G, Yagel O, Rashad R, Ibrahimli M et al. Apixaban vs. warfarin in patients with left ventricular thrombus: a prospective multicentre randomized clinical trial. European Heart Journal – Cardiovascular Pharmacotherapy. 2022;8(7):660–7. DOI: 10.1093/ehjcvp/pvab057

20. Ali Z, Isom N, Dalia T, Sami F, Mahmood U, Shah Z et al. Direct oral anticoagulant use in left ventricular thrombus. Thrombosis Journal. 2020;18(1):29. DOI: 10.1186/s12959-020-00242-x

21. Bass ME, Kiser TH, Page RL, McIlvennan CK, Allen LA, Wright G et al. Comparative effectiveness of direct oral anticoagulants and warfarin for the treatment of left ventricular thrombus. Journal of Thrombosis and Thrombolysis. 2021;52(2):517–22. DOI: 10.1007/s11239-020-02371-6

22. Daher J, Da Costa A, Hilaire C, Ferreira T, Pierrard R, Guichard JB et al. Management of Left Ventricular Thrombi with Direct Oral Anticoagulants: Retrospective Comparative Study with Vitamin K Antagonists. Clinical Drug Investigation. 2020;40(4):343–53. DOI: 10.1007/s40261-020-00898-3

23. Hitt N, Putz J, Kladstrup C, Anderson D, Hamilton R, Koranne K et al. Direct Oral Anticoagulants As a Treatment for Left Ventricular Thrombus. Chest. 2021;160(4):A264. DOI: 10.1016/j.chest.2021.07.272

24. Jaidka A, Zhu T, Lavi S, Johri A. Treatment of Left Ventricular Thrombus Using Warfarin Versus Direct Oral Anticoagulants Following Anterior Myocardial Infarction. Canadian Journal of Cardiology. 2018;34(10):S143. DOI: 10.1016/j.cjca.2018.07.194

25. Jones DA, Wright P, Alizadeh MA, Fhadil S, Rathod KS, Guttmann O et al. The use of novel oral anticoagulants compared to vitamin K antagonists (warfarin) in patients with left ventricular thrombus after acute myocardial infarction. European Heart Journal - Cardiovascular Pharmacotherapy. 2021;7(5):398–404. DOI: 10.1093/ehjcvp/pvaa096

26. Lim CW, Mamat RM, Hishammudin IA, Danuri N, Najme Khir R, Ibrahim KS et al. Left Ventricular Thrombus: Patient Characteristics and Treatment from a Single Tertiary Centre’s Experience. International Journal of Cardiology. 2019;297:20–1. DOI: 10.1016/j.ijcard.2019.11.056

27. Mihm AE, Hicklin HE, Cunha AL, Nisly SA, Davis KA. Direct oral anticoagulants versus warfarin for the treatment of left ventricular thrombosis. Internal and Emergency Medicine. 2021;16(8):2313–7. DOI: 10.1007/s11739-021-02788-8

28. Willeford A, Zhu W, Stevens C, Thomas IC. Direct Oral Anticoagulants Versus Warfarin in the Treatment of Left Ventricular Thrombus. Annals of Pharmacotherapy. 2021;55(7):839–45. DOI: 10.1177/1060028020975111

29. Xu Z, Li X, Li X, Gao Y, Mi X. Direct oral anticoagulants versus vitamin K antagonists for patients with left ventricular thrombus. Annals of Palliative Medicine. 2021;10(9):9427–34. DOI: 10.21037/apm-21-1683

30. Yunis A, Seese L, Stearns B, Genuardi M, Thoma F, Kilic A. Direct Oral Anticoagulants Are Effective Therapy in Treating Left Ventricular Thrombi. Journal of the American College of Cardiology. 2020;75(11):948. DOI: 10.1016/S0735-1097(20)31575-8

31. Zhang Z, Si D, Zhang Q, Qu M, Yu M, Jiang Z et al. Rivaroxaban versus Vitamin K Antagonists (warfarin) based on the triple therapy for left ventricular thrombus after ST-Elevation myocardial infarction. Heart and Vessels. 2022;37(3):374–84. DOI: 10.1007/s00380-021-01921-z

32. Michael F, Natt N, Shurrab M. Direct Oral Anticoagulants vs Vitamin K Antagonists in Left Ventricular Thrombi: A Systematic Review and Meta-analysis. CJC Open. 2021;3(9):1169–81. DOI: 10.1016/j.cjco.2021.04.007