By Michael H. Crawford, MD, Editor
Synopsis: A small pilot randomized controlled trial, plus a meta-analysis including four other randomized controlled trials, of direct oral anticoagulants compared to warfarin for the treatment of left ventricular thrombus after ST-elevation myocardial infarction has shown that there were no significant differences in the two regimens regarding thrombus resolution and major bleeding events at three-month follow-up.
Source: Jenab Y, Sadeghipour P, Mohseni-Badalabadi R, et al. Direct oral anticoagulants or warfarin in patients with left ventricular thrombus after ST-elevation myocardial infarction: A pilot trial and a prespecified meta-analysis of randomized trials. EuroIntervention. 2025;21(1):82-92.
Although more convenient for the patient, there is little evidence that direct oral anticoagulants (DOACs) are as efficacious and safe as warfarin in the treatment of left ventricular thrombus (LVT) after acute ST-elevation myocardial infarction (STEMI). Thus, this group from two centers in Tehran, Iran, conducted a pilot randomized controlled trial (RCT) of rivaroxaban vs. adjusted warfarin for this purpose (REWARF-STEMI). In addition, the investigators added their data to those of four other RCTs involving 27 to 79 such patients and performed a meta-analysis of the entire dataset.
REWARF-STEMI was an open-label, parallel group, blinded end-point RCT. It enrolled adults within two weeks of a STEMI who had an LVT on a non-contrast two-dimensional echocardiogram analyzed by a core laboratory. Excluded were those with contraindications to a DOAC, such as a mechanical valve, rheumatic heart disease, antiphospholipid syndrome, active bleeding, cardiogenic shock, an estimated glomerular filtration rate (eGFR) < 30 mL/min, or who were taking a DOAC for other reasons.
In addition to clopidogrel 75 mg/day and aspirin 80 mg/day, the subjects were randomized to rivaroxaban 15 mg/day or warfarin with an adjusted international normalized ratio (INR) of 2.0 to 2.5. After seven days, aspirin was stopped. The primary endpoint was complete resolution of the LVT at three months post-myocardial infarction (MI). Secondary endpoints included stroke or systemic emboli (S/SE) and major adverse cardiac events (MACE), which included recurrent MI, S/SE, and cardiovascular death. The safety endpoint was major bleeding.
Between 2020 and 2022, 50 patients were enrolled (mean age 55 years, 18% women). An anterior MI was present in 90% of the patients, 49% underwent a percutaneous coronary intervention (PCI), and one had a balloon angioplasty followed by emergency coronary bypass surgery. One patient died suddenly in his sleep, so 49 patients completed the three-month follow-up with an echocardiogram.
The primary outcome occurred in 19 of the 25 (76%) patients taking rivaroxaban compared to 13 of 24 (54%) patients taking warfarin (relative risk [RR], 1.40; 95% confidence interval [CI], 0.91 to 2.15; P = NS). There were no S/SE or MACE observed, and two patients taking rivaroxaban had major bleeding. The meta-analysis included a total of 228 patients: 116 receiving a DOAC (65 taking rivaroxaban and 51 taking apixaban) and 112 on warfarin. The primary endpoint occurred in 81% of patients taking a DOAC compared to 71% of patients taking warfarin (RR, 1.14; 95% CI, 0.98 to 1.32; P = 0.08). Major bleeding occurred in 12% of patients taking a DOAC compared to 8% of patients taking warfarin (RR, -0.06; 95% CI, -0.12 to 0.00; P = 0.05). The authors concluded that in patients with LVT following STEMI, DOAC use results in similar LVT resolution and major bleeding compared to warfarin at three months.
Commentary
The issue of how to treat patients with LV thrombus after STEMI continues to be controversial because there are no large, randomized trials and there probably never will be. (Note: I spoke too soon. A larger randomized trial of rivaroxaban vs. warfarin in more than 200 patients conducted in Pakistan [RIVAWAR] was presented at the recent American College of Cardiology Annual Scientific Sessions and showed similar results to the Iranian study. No manuscript was available at the time of this writing.) Thus, this small, randomized trial added to the other small trials in a meta-analysis is of interest.
The investigators showed that after three months, three-quarters of the DOAC-treated patients and about half of the warfarin-treated patients had complete resolution by echocardiographic imaging, and there were no S/SE or MACE in either group. Two patients taking DOACs had a major bleed. These results support the concept that either therapy is reasonable. DOACs are easier to use and perhaps provide more consistent anticoagulation. It is tempting to conclude that the somewhat less efficaciousness but fewer bleeds with warfarin is the result of inconsistent anticoagulation because of the difficulty in maintaining a steady anticoagulation effect with warfarin. Based on the older small trials the American Heart Association already has endorsed DOACs as a viable option.1
There are limitations to REWARF-STEMI. Not only was it small, but there were few women enrolled, and the average age of the population was surprisingly low (mean age 55 years). Contrast echocardiography was not used, which probably reduced the sensitivity for detecting thrombi, but other studies have shown the specificity of a thrombus identified by two-dimensional echocardiography is quite high (up to 98%). Also, only two centers were involved in the study. In addition, they used a fixed dose of rivaroxaban (15 mg/day). Perhaps the 20-mg dose would have been more effective, but at a cost of more bleeding. One of the studies in the meta-analysis used 20 mg.
Some believe that apixaban is more effective and safer than rivaroxaban. Three of the trials in the meta-analysis used apixaban 5 mg twice per day. In addition, each of the trials used different antiplatelet strategies, which could affect the risks and efficacy of the anticoagulant therapy. REWARF-STEMI patients were taking clopidogrel alone after one week of dual antiplatelet therapy.
Finally, only about half the patients in REWARF-STEMI had a PCI. Despite these limitations, it may be reasonable to ask the patient which agent they prefer and go that way unless there are contraindications to the agent desired.
Michael H. Crawford, MD, is Professor Emeritus of Medicine and Consulting Cardiologist, UCSF Health, San Francisco.
Reference
1. Levine GN, McEvoy JW, Fang JC, et al; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Stroke Council. Management of patients at risk for and with left ventricular thrombus: A scientific statement from the American Heart Association. Circulation. 2022;146(15):e205-e223.
A small pilot randomized controlled trial, plus a meta-analysis including four other randomized controlled trials, of direct oral anticoagulants compared to warfarin for the treatment of left ventricular thrombus after ST-elevation myocardial infarction has shown that there were no significant differences in the two regimens regarding thrombus resolution and major bleeding events at three-month follow-up.
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