Cracking the clot: the RIVAWAR trial challenges warfarin’s reign in left ventricular thrombus post-acute coronary syndrome

Evidence before this study

Left ventricular thrombosis (LVT) is a severe complication that often arises in patients with left ventricular systolic dysfunction, particularly within 1–14 days after a ST-segment elevation myocardial infarction (STEMI), and is associated with increased risks of stroke, embolization, and mortality.^1,2 Despite modern reperfusion therapy, the prevalence of LVT remains notable, ranging from 2 to 22%.^3,4 It is more frequent in patients with anterior STEMI and in patients with severe ventricular dysfunction and varies based on the imaging modality employed for detection.^5–7

Vitamin K antagonists, such as warfarin, have been the standard treatment for LVT, though they require monitoring and have dietary interactions.⁸In contrast, direct oral anticoagulants, including rivaroxaban, have gained attention as alternatives, offering advantages such as fewer food and drug interactions, a lower risk of bleeding, and no requirement for routine laboratory monitoring.⁹ The 2023 ESC Guidelines for management of acute coronary syndromes (ACS) recommend that oral anticoagulation therapy [warfarin or direct anticoagulants (DOAC)] should be considered for 3–6 months in patients with confirmed LVT (class IIa, level of evidence C).¹⁰ Nonetheless, the evidence supporting DOAC use for LVT, particularly in the context of ACS, remains limited.^11,12

Contribution to clinical practice

The RIVAWAR trial supports the use of rivaroxaban as a non-inferior alternative to warfarin for LV thrombus management, offering similar efficacy and safety with potential advantages in clinical practice.

Study design

This investigator-initiated, single-centre trial (conducted in Karachi, Pakistan) was an open-label, randomized study aimed at assessing the safety and efficacy of rivaroxaban 20 mg compared with dose-adjusted warfarin (target INR 2–3) in a 2:1 ratio over a 3-month period in patients with acute LVT following an ACS. All participants received dual antiplatelet therapy (DAPT) for the first month, followed by single antiplatelet therapy for the subsequent 8 weeks, in combination with an oral anticoagulant. (ClinicalTrials.gov Identifier: NCT04970576).

Key exclusion criteria included a prior history of cardiomyopathy, previous stroke with residual neurological deficits, and valvular atrial fibrillation.

Study results

A total of 261 patients with acute LVT (mean age 54.5 years; 79.3% male) were randomized to receive either rivaroxaban (n = 171) or warfarin (n = 90) for a duration of 3 months. Among these, 90.4% experienced a STEMI and 9.6% a non-STEMI, with 85.1% having undergone percutaneous coronary intervention. Left ventricular ejection fraction was ≤35% in 93.9% of participants.

The primary outcome was the presence of LVT on transthoracic echocardiography at 12 weeks post-randomization. At 1 month, a higher proportion of patients in the rivaroxaban group showed resolution of LVT compared with the warfarin group [33 patients (20.1%) vs. 7 patients (8.3%); risk difference (RD), 11.8%; odds ratio (OR) 2.41; P = 0.017]. However, at 3 months, clot resolution rates were nearly identical between groups: 95.8% in the rivaroxaban arm vs. 96.6% in the warfarin arm (RD, −0.8%; OR, 0.98; P = 0.88).

Secondary outcomes were also comparable between the two groups. All-cause mortality occurred in 3.5% of the rivaroxaban group vs. 3.3% in the warfarin group; ischaemic stroke in 3.5 vs. 1.1%; and major bleeding.¹³ in 2.3 vs. 1.1%, respectively. Follow-up was ended at the 3-month mark for all outcomes.

In perspective

The RIVAWAR trial is one of the first randomized controlled studies to compare rivaroxaban and warfarin for the treatment of LVT following ACS. While LVT incidence has declined with modern reperfusion and antithrombotic therapies, embolic complications remain a serious concern requiring effective anticoagulation.

This trial found no significant differences between rivaroxaban and warfarin in terms of thrombus resolution at 3 months. Furthermore, there were no significant differences in the secondary outcomes of stroke or major bleeding. These findings, consistent with prior observational data, support rivaroxaban as a feasible alternative to warfarin, particularly given its predictable dosing and lack of need for monitoring.

The study was not designed to assess clinical outcomes such as stroke or major bleeding. However, the numerically higher stroke rate observed in the rivaroxaban group warrants attention, though it may be a result of chance due to the limited sample size. Similarly, the numerically higher rate of major bleeding should be acknowledged. Patients received DAPT for 1 month, followed by single antiplatelet therapy for the next 2 months, in combination with oral anticoagulation. Previous studies have shown that ‘triple therapy’ increases the risk of bleeding,^9,14 making it relevant to determine the timing of major bleeding events and whether a shorter DAPT duration could have mitigated bleeding risk. Additional study limitations include its single-centre and open-label design, reliance on echocardiography (rather than Magnetic Resonance Imaging) without core lab adjudication, and a short follow-up period of 3 months. Furthermore, the relatively young age of the myocardial infarction population—characteristic of this geographic region—may limit generalizability.

Despite these limitations, RIVAWAR provides valuable prospective evidence in a space largely informed by observational data. With several international randomized trials underway (e.g. NCT06013020, NCT05892042, and NCT05705089), RIVAWAR contributes meaningfully to the evolving understanding of LVT management post-ACS.

Funding

None declared.

Data availability

No new data were generated or analysed in support of this research.

References

Author notes