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The APERITIF trial evaluated the efficacy of adding very low-dose rivaroxaban (2.5 mg twice daily) to dual antiplatelet therapy (DAPT) for the prevention of left ventricular (LV) thrombus in patients following anterior ST-segment elevation myocardial infarction (STEMI).
Primary results showed that LV thrombus occurred in 13.7% of the rivaroxaban group compared to 16.6% in the DAPT-only group, a difference that was not statistically significant (P = .34).
While major bleeding rates remained low and comparable between groups, the addition of rivaroxaban was associated with a significant increase in minor bleeding (BARC type 1) events.
The study highlights the utility of contrast-enhanced cardiac magnetic resonance (CMR) imaging for the sensitive detection of LV thrombus, revealing a higher-than-expected incidence even in the era of modern reperfusion therapy.
Background: The Persistent Threat of LV Thrombus
Left ventricular (LV) thrombus remains a serious and relatively common complication following anterior ST-segment elevation myocardial infarction (STEMI). Despite the widespread implementation of primary percutaneous coronary intervention (PCI) and potent dual antiplatelet therapy (DAPT), patients with large anterior wall infarctions remain at high risk. The pathophysiology is rooted in Virchow’s triad: blood stasis in an akinetic or dyskinetic apex, endocardial injury from the infarction, and a systemic hypercoagulable state triggered by the acute event.
The clinical significance of LV thrombus lies in its potential for systemic embolization, most notably ischemic stroke. Historically,
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the incidence of LV thrombus was as high as 40% in the pre-thrombolytic era. While modern reperfusion has reduced this, contemporary studies using cardiac magnetic resonance (CMR) imaging—the gold standard for detection—suggest that the incidence remains between 10% and 25% for anterior STEMIs. Current clinical guidelines are somewhat ambiguous regarding the prophylactic use of oral anticoagulants in this setting, often reserving them for patients with documented thrombus rather than using them as a preventive measure. The APERITIF (Anticoagulant Prevention of LV Thrombus with Rivaroxaban) trial sought to provide definitive evidence on whether a low-dose Factor Xa inhibitor could bridge this therapeutic gap.
Study Design and Methodology
The APERITIF trial was a multicenter, open-label, randomized clinical trial with a blinded-end point design. Conducted across 29 centers in France, the study was nested within the FRENCHIE (French Cohort of Myocardial Infarction Evaluation) registry. The study enrolled 560 patients between October 2021 and January 2023 who presented with an anterior STEMI and had undergone successful coronary angiography or PCI.
Participants were randomized in a 1:1 ratio to one of two treatment arms:
Intervention Group
Patients received standard DAPT (aspirin ≤100 mg/day plus either ticagrelor 90 mg BID or clopidogrel 75 mg/day) combined with low-dose rivaroxaban (2.5 mg twice daily) for a duration of four weeks.
Control Group
Patients received standard DAPT alone for four weeks.
The primary endpoint was the presence of an LV thrombus detected by contrast-enhanced CMR at 1 month post-infarction. Secondary endpoints included the largest diameter of the thrombus, the incidence of major adverse cardiovascular events (MACE), including death, recurrent MI, and stroke, and safety outcomes defined by the Bleeding Academic Research Consortium (BARC) criteria.
Key Findings: Efficacy and Safety
Of the 560 patients enrolled (mean age 61.1 years; 21.6% female), 545 completed the 1-month follow-up with the primary endpoint assessment. The results indicated that the addition of rivaroxaban did not meet the threshold for statistical superiority.
Primary Endpoint: LV Thrombus Incidence
In the intention-to-treat analysis, LV thrombus was detected in 38 patients (13.7%) in the rivaroxaban group and 47 patients (16.6%) in the DAPT-only group. The absolute difference of -2.9% (95% CI, -8.9% to 3.2%) was not statistically significant (P = .34). This suggests that while there was a numerical reduction, low-dose rivaroxaban was not effective enough to change clinical practice based on this study’s power.
Secondary Clinical Outcomes
There were no significant differences between the two groups regarding MACE or the physical characteristics of the thrombi. The mean diameter of the thrombi detected was similar across both arms of the trial. Stroke rates were exceptionally low in both groups, likely due to the short follow-up period and the relatively small sample size for such rare events.
Safety and Bleeding
Safety data revealed a nuanced picture. Major bleeding (BARC type 2 or higher) was rare and did not differ significantly between groups: 1.5% in the rivaroxaban group versus 0.7% in the DAPT group (difference 0.7%; 95% CI, -1.3% to 3.1%). However, minor bleeding (BARC type 1) was more than twice as common in the rivaroxaban arm, occurring in 16.4% of patients compared to 7.2% in the control arm (difference 9.3%; 95% CI, 3.6%-14.8%). This increase in nuisance bleeding can impact patient adherence and quality of life in the early post-MI period.
Expert Commentary and Clinical Interpretation
The results of the APERITIF trial pose several important questions for the cardiology community. First, the 16.6% incidence of LV thrombus in the control group confirms that this remains a high-frequency complication in anterior STEMI, even with modern PCI. The study’s use of CMR is a major strength, as traditional transthoracic echocardiography (TTE) frequently misses small or mural thrombi.
Why did low-dose rivaroxaban fail to show a significant benefit? One possibility is the dose itself. The 2.5 mg BID dose was chosen based on the ATLAS ACS 2-TIMI 51 trial, which showed a reduction in MACE but was not specifically powered for LV thrombus prevention. It is possible that a higher dose, such as 10 mg or 15 mg daily, might be required to overcome the stasis-driven thrombotic environment of a dyskinetic LV apex. However, higher doses would almost certainly increase the risk of major bleeding when combined with DAPT.
Furthermore, the study may have been underpowered to detect a modest but clinically relevant benefit. The investigators noted that a modest effect cannot be entirely excluded based on the confidence intervals. The trial was designed with an expected higher baseline rate of thrombus, and the slightly lower-than-anticipated event rate in the control group may have diluted the statistical power.
From a guideline perspective, these findings support the current conservative approach: routine prophylaxis with oral anticoagulants (OAC) in all anterior STEMI patients is not recommended. Instead, a strategy of early imaging (preferably CMR in high-risk cases) followed by targeted treatment of documented thrombi remains the most evidence-based path.
Conclusion
The APERITIF trial demonstrates that the addition of low-dose rivaroxaban to DAPT for one month following anterior STEMI does not significantly reduce the formation of LV thrombi. While the safety profile regarding major bleeding was acceptable, the increase in minor bleeding and the lack of a clear efficacy signal suggest that this triple therapy regimen should not be routinely adopted. Future research may need to focus on identifying specific high-risk subgroups—such as those with very low ejection fractions or specific apical wall motion abnormalities—who might derive more significant benefit from intensified antithrombotic strategies.
Funding and ClinicalTrials.gov
The APERITIF trial was supported by grants from the French Ministry of Health (Programme Hospitalier de Recherche Clinique). The study is registered at ClinicalTrials.gov (Identifier: NCT05077683).
References
1. Puymirat E, Soulat G, Lattuca B, et al. Low-Dose Rivaroxaban to Prevent Left Ventricular Thrombosis After Anterior Myocardial Infarction: The APERITIF Randomized Clinical Trial. JAMA Cardiol. 2026 Feb 25:e260026. doi: 10.1001/jamacardio.2026.0026.
2. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366(1):9-19.
3. Robinson AA, Jain A, Gentry M, McNamara RL. Left ventricular thrombus after acute myocardial infarction: a review of contemporary management. Curr Treat Options Cardiovasc Med. 2016;18(3):16.
4. Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction. J Am Coll Cardiol. 2016;67(10):1235-1250.
