Anticoagulation in Post MI LV Thrombus Trial in Nepal

Summary

Introduction: The prevalence of left ventricular(LV) thrombus after acute myocardial infarction has decreased with thrombolysis and primary angioplasty intervention worldwide. However, most of the patients in our country present late after the onset of ischemia resulting in a comparable increase proportion of late presentation MI compared to developed countries. This delayed presentation is associated with the increased incidence of LV thrombus, associated with increased cerebrovascular and cardiovascular events resulting in increased morbidity and mortality. The Vitamin K Antagonist Warfarin is indicated in recent guidelines for the duration of 3-6 months. The use of Warfarin is less in our part of the world due to the requirement of frequent International Normalized Ration (INR) monitoring and dietary restrictions. Novel oral anticoagulants (NOACs) are an alternate option for such hindrance to the treatment of LV thrombus. This research will help assess the safety and efficacy of Rivaroxaban, one of the NOACs compared to warfarin. Objectives: Our aim will be to compare the efficacy of rivaroxaban compared to warfarin in the complete resolution of post-MI LV thrombus. The primary efficacy endpoint of our study will be a resolution of LV thrombus as assessed by cardiac MRI at the end of 3 months of the study period. The secondary endpoint will be the comparison of the safety of both drugs measured by the incidence of major bleeding and embolic events. Methods: The patients who present late after acute MI in our center with LV thrombus will be enrolled in our study. The diagnosis of LV thrombus will be diagnosed by cardiac MRI, which is considered the gold standard for the diagnosis. The patients then will be randomized in a 1:1 ratio to either warfarin or rivaroxaban within 24 hours of diagnosis of LV thrombus. The warfarin group will be prescribed the warfarin in the dose of 5mg daily and the dose titrated according to the INR value to maintain the INR range of 2 to 3. Rivaroxaban group will be prescribed 15 to 20mg according to the indication. The research group consisting of the principal investigator and coinvestigators will be responsible for the recruitment and overall study procedures.

Timeline

Start

2023-06-19

Primary completion

2026-03

Completion

2026-04

Publications

• Background Bhattarai S, Aryal A, Pyakurel M, Bajracharya S, Baral P, Citrin D, Cox H, Dhimal M, Fitzpatrick A, Jha AK, Jha N, Karmacharya BM, Koju R, Maharjan R, Oli N, Pyakurel P, Sapkota BP, Shrestha R, Shrestha S, Spiegelman D, Vaidya A, Shrestha A. Cardiovascular disease trends in Nepal - An analysis of global burden of disease data 2017. Int J Cardiol Heart Vasc. 2020 Jul 31;30:100602. doi: 10.1016/j.ijcha.2020.100602. eCollection 2020 Oct.
• Background Adhikari, C. M., Acharya, K. P., Manandhar, R., Sherpa, K., Tamrakar, R., Bogati, A., Singh, S. K., Kansakar, S., Yadav, D. N., Dhungana, M., Dhungel, S., Baniya, B., Joshi, S., Rajbhandari, S., Pandey, R., Raut, R., Prajapati, D., KC, S. S., Adhikari, J., Adhikari, A., Gautam, B., Najmy, S., Poudel, R., Timalsina, B. K., Karki, P., Poudel, S., Thakur, K. K., Limbu, D., Nepal, H. P., Sharma, M., Rauniyar, B. K., Rajbhandari, R., Limbu, Y. R., Maskey, A., Malla, R., Sharma, D., & KC, M. B. (2020). Shahid Gangalal National Heart Centre-ST-elevation Myocardial infarction Registry (SGNHC-STEMI-Registry), Nepal. Nepalese Heart Journal, 17(1), 7-16. https://doi.org/10.3126/njh.v17i1.28795
• Background Gottdiener JS, Gay JA, VanVoorhees L, DiBianco R, Fletcher RD. Frequency and embolic potential of left ventricular thrombus in dilated cardiomyopathy: assessment by 2-dimensional echocardiography. Am J Cardiol. 1983 Dec 1;52(10):1281-5. doi: 10.1016/0002-9149(83)90588-x.
• Background Gottdiener JS, Massie B, Ammons SB, et al. Prevalence of left ventricular thrombus in dilated cardiomyopathy: the WATCH trial. J Am J Cardiol 2003;41:202.
• Background Srichai MB, Junor C, Rodriguez LL, Stillman AE, Grimm RA, Lieber ML, Weaver JA, Smedira NG, White RD. Clinical, imaging, and pathological characteristics of left ventricular thrombus: a comparison of contrast-enhanced magnetic resonance imaging, transthoracic echocardiography, and transesophageal echocardiography with surgical or pathological validation. Am Heart J. 2006 Jul;152(1):75-84. doi: 10.1016/j.ahj.2005.08.021.
• Background Keeley EC, Hillis LD. Left ventricular mural thrombus after acute myocardial infarction. Clin Cardiol. 1996 Feb;19(2):83-6. doi: 10.1002/clc.4960190203.
• Background Pizzetti G, Belotti G, Margonato A, Carlino M, Gerosa S, Carandente O, Chierchia SL. Thrombolytic therapy reduces the incidence of left ventricular thrombus after anterior myocardial infarction. Relationship to vessel patency and infarct size. Eur Heart J. 1996 Mar;17(3):421-8. doi: 10.1093/oxfordjournals.eurheartj.a014875.
• Background Bhatnagar SK, al-Yusuf AR. Effects of intravenous recombinant tissue-type plasminogen activator therapy on the incidence and associations of left ventricular thrombus in patients with a first acute Q wave anterior myocardial infarction. Am Heart J. 1991 Nov;122(5):1251-6. doi: 10.1016/0002-8703(91)90563-w.
• Background Ezekowitz MD, Wilson DA, Smith EO, Burow RD, Harrison LH Jr, Parker DE, Elkins RC, Peyton M, Taylor FB. Comparison of Indium-111 platelet scintigraphy and two-dimensional echocardiography in the diagnosis of left ventricular thrombi. N Engl J Med. 1982 Jun 24;306(25):1509-13. doi: 10.1056/NEJM198206243062502.
• Background Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018 Jan 7;39(2):119-177. doi: 10.1093/eurheartj/ehx393. No abstract available.
• Background O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX. 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. J Am Coll Cardiol. 2013 Jan 29;61(4):e78-e140. doi: 10.1016/j.jacc.2012.11.019. Epub 2012 Dec 17. No abstract available.
• Background Keita I, Aubin-Auger I, Lalanne C, Aubert JP, Chassany O, Duracinsky M, Mahe I. Assessment of quality of life, satisfaction with anticoagulation therapy, and adherence to treatment in patients receiving long-course vitamin K antagonists or direct oral anticoagulants for venous thromboembolism. Patient Prefer Adherence. 2017 Sep 25;11:1625-1634. doi: 10.2147/PPA.S131157. eCollection 2017.
• Background Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
• Background Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375. Epub 2021 May 24. No abstract available.
• Background Saleh Y, Al-Abcha A, Abdelkarim O, Elwany M, Abdelfattah OM, Abdelnabi M, Almaghraby A. Meta-Analysis Comparing the Effect of Rivaroxaban Versus Vitamin K Antagonists for Treatment of Left Ventricular Thrombi. Am J Cardiol. 2021 Dec 15;161:123-125. doi: 10.1016/j.amjcard.2021.09.009. Epub 2021 Oct 14. No abstract available.

Drugs

Indications