Anticoagulation in Post MI LV Thrombus Trial in Nepal

Cardiovascular disease is the leading cause of mortality and morbidity among non-communicable diseases worldwide including in Nepal. Myocardial infarction(MI) is the main disease among cardiovascular diseases. [i] MI is also the main reason for hospitalization in the cardiac centers of our country. [ii] There is an additional burden of late presentation of MI in our setting due to lack of proper awareness, limited access to health care and improper referral mechanism. In the hospital-based registry in 2018, more than 65% of acute MI presented after the eligible time frame for primary angioplasty or thrombolysis. [iii] The incidence of the formation of left ventricular (LV) thrombus is increased with the late presentation. Worldwide, the prevalence of LV thrombus before the era of primary angioplasty was around 31-57%. [iv],[v],[vi] After the start of the primary angioplasty techniques, the prevalence of post-MI LV thrombus has decreased to around 15%.[vii] However, it is still associated with increased risks of embolic events and mortality.[viii],[ix],[x] European and American guidelines have recommended using vitamin K antagonist (VKA) for a minimum of 3-6 months as a class IIa, LOE c, with duration individualized to bleeding risk with a target of international normalized ratio (INR) of 2.5 (range of 2 to 3). [xi],[xii] Non-VKA oral anticoagulants (NOACs) in addition to the dual antiplatelet therapy in these patients are attractive alternatives because of their potential efficacy and safety along with ease of administration, lack of requirement for INR monitoring or dietary restrictions resulting in overall improvement of life.[xiii] However, there is no randomized control trial comparing warfarin and NOACs. There are two ongoing trials NCT01556659 and NCT03764241. The recommendation is more relevant to us as there is an overburden of patients presenting late due to various geographical and financial reasons. This study was designed for the evaluation of anticoagulation effects among the acute ST elevation Myocardial Infarction (STEMI) with LV thrombus in complete resolution of LV thrombus. The investigators aim to compare Warfarin to Rivaroxaban in the management of post-myocardial infarction left ventricular thrombus in our part of the world.

Data management and Analysis Plan:

Independent data safety and monitoring board will be formed and will be responsible for the safety concerns of the research participants. Data will be collected and entered in the computer-based CRF constructed using the password-protected free software at https://www.kobotoolbox.org. The data will be accessed by the principal investigator and the research officer only. The data will be anonymized before statistical analysis which will be performed by the separate coinvestigators responsible for the data analysis. Appropriate statistical tests will be used for measuring association and correlation. A 'P' value of less than 0.05 will be considered to be significant.

Dissemination Plan:

The findings of the study will be published in a peer-reviewed journal and presented at national and international conferences.

Inclusion criteria

• Patients aged >18 years hospitalized with the diagnosis of acute STEMI and
• Presence of LV thrombus which is confirmed with cardiac MRI.

Exclusion criteria

• Bleeding risk Active bleeding; history of intracranial hemorrhage; clinically significant gastrointestinal bleeding within 12 months before randomization; severe thrombocytopenia (<50×109/L), or anemia (i.e., hemoglobin <90 g/L) at screening or pre-randomization; Liver function Child-Pugh B or C; untreated arterial aneurysm, arterial or venous malformation and aorta dissection; and body weight <40 kg.
• Undergoing anticoagulation therapy
• Cardiovascular condition Cardiac shock; uncontrolled blood pressure (SBP ≥180 mmHg); planned CABG within 3 months; suspicious Pseudo-ventricular aneurysm
• Concomitant diseases Severe chronic or acute renal failure (CrCl <50 mL/min at screening or pre-randomization); significant liver disease; current substance abuse (drug or alcohol) problem; life expectancy to less than 12 months; Known allergies, or intolerance to rivaroxaban; Woman who is currently pregnant, or breastfeeding; and Other hypercoagulable states, such as a malignant tumor, SLE
• Other conditions adjudicated by investigators to be unsuitable for anticoagulation
• Pregnant women and participants with any cognitive impairment.