Vesalio Says NATURE Trial Meets Primary Endpoint for enVast Coronary Thrombectomy

Vesalio said its NATURE randomized trial met its primary efficacy endpoint, with enVast-assisted coronary thrombectomy reducing a biomarker-based measure of infarct size by nearly 26% compared with standard care in patients undergoing primary PCI for ST-segment elevation myocardial infarction with large thrombus burden.

The result gives the privately held medical-device company a positive controlled-trial readout for a stent-based clot retriever in a difficult STEMI subgroup. It does not establish that the device reduces mortality or stroke, and the company-reported safety comparisons involved few events. The most direct finding is narrower: patients assigned to enVast before conventional PCI had less myocardial injury on the trial’s prespecified primary measure.

Vesalio announced the NATURE results on Aug. 29 as the study was presented at ESC Congress 2026 in Munich. The prospective, multicenter trial randomized 154 patients at 11 centers in a 1:1 ratio to enVast-assisted mechanical thrombectomy followed by conventional PCI or to standard care. Principal investigator Marco Valgimigli of Cardiocentro Ticino Institute presented the study in an ESC late-breaking clinical-trials session.

NATURE used CK-MB exposure as its primary infarct-size measure

The primary endpoint was infarct size assessed by the area under the curve for creatine kinase-MB activity, commonly abbreviated CK-MB AUC. Vesalio reported a nearly 26% reduction with enVast compared with standard care, with a p value of 0.001. The company described the result as a reduction in myocardial damage rather than a direct measure of long-term clinical benefit.

That distinction matters because NATURE was designed to detect a treatment effect on myocardial injury, not to prove a reduction in death, recurrent heart attack or stroke. The trial’s design paper, published in Cardiovascular Revascularization Medicine before the results, specified CK-MB AUC as the primary endpoint and calculated that 148 patients with complete primary-endpoint assessment would provide 90% power to detect a 30% decrease. Vesalio said 154 patients were randomized in the completed study.

A cardiac magnetic resonance imaging assessment provided a second look at infarct size. According to Vesalio, CMR at day three showed a 25% relative reduction in infarct size as a percentage of left ventricular mass in the enVast group. The company characterized that secondary result as a positive trend rather than reporting it as a separately proven efficacy endpoint, so it should not be read as equivalent to the statistically significant primary result.

The intervention is aimed at a specific procedural problem. In STEMI, a coronary artery is acutely blocked and rapid restoration of blood flow is central to limiting damage to heart muscle. Large thrombus burden can complicate primary PCI because clot may remain in the vessel or fragment during treatment, potentially impairing blood flow at the microvascular level even after the main artery has been reopened. NATURE tested whether physically retrieving that clot before conventional PCI could reduce the amount of myocardial injury.

Thirty-day safety numbers favored enVast, but event counts were small

Vesalio also reported descriptive 30-day safety findings. No strokes occurred in the enVast arm, compared with a 1.3% stroke rate in the control arm. The company reported no deaths in the enVast group versus 2.6% in the control group, while major adverse cardiovascular events were 1.3% and 3.8%, respectively.

Those percentages are directionally favorable, but NATURE was not presented as a large outcomes trial powered to establish superiority for mortality, stroke or a composite clinical endpoint. With 154 randomized patients, a difference of only a few events can materially change the percentages. The safety data therefore add context to the efficacy result without supporting a broad claim that enVast has already been shown to improve hard clinical outcomes.

The trial design adds safeguards around those event assessments. Its published protocol says clinical events are adjudicated by an independent Clinical Events Committee, while electrocardiograms, coronary angiography, cardiac magnetic resonance imaging and echocardiography are reviewed by central core laboratories. Follow-up was scheduled at roughly 30 days, five months and one year, meaning the 30-day figures announced at ESC represent only part of the planned observation period.

Vesalio positions enVast as a coronary clot retriever used alongside aspiration. The company says the device is designed to engage thrombus from distal to proximal as it is withdrawn, with the goal of removing clot before the rest of the PCI procedure. Vesalio announced U.S. FDA 510(k) clearance for the coronary thrombectomy platform in December 2025 and also markets the system in Europe.

The result tests a selective strategy after routine aspiration fell out of favor

NATURE arrives against a cautious clinical backdrop for thrombectomy during primary PCI. Large randomized studies of routine manual thrombus aspiration failed to show an overall clinical benefit, and one raised a stroke concern. The 2023 ESC acute coronary syndrome guidelines therefore say routine thrombus aspiration is not recommended. They leave room for aspiration in selected cases when a large residual thrombus burden remains after the vessel is opened.

enVast is not simply another test of routine manual aspiration. NATURE focused on STEMI patients with large thrombus burden and evaluated a stent-based retrieval system as an adjunct to conventional PCI. That narrower population and different device mechanism are important when comparing the trial with older thrombectomy studies. A positive infarct-size endpoint in that selected group does not reverse the evidence against routine aspiration for all STEMI patients.

The study also stops short of answering whether less CK-MB release will translate into fewer later clinical events. Infarct size is clinically relevant because larger myocardial injury is generally associated with worse ventricular function and prognosis, but translating a biomarker difference into a durable benefit requires longer follow-up and, in many cases, larger trials. NATURE’s planned one-year follow-up may provide additional information, although the study’s size limits the precision of uncommon event estimates.

For Vesalio, the immediate result is a successful primary-endpoint readout for a device the company has already moved into commercial markets. For clinicians, the more important question is whether the reduction in myocardial injury can be reproduced and whether it leads to meaningful differences in symptoms, ventricular function or major cardiovascular events. The Aug. 29 ESC presentation establishes the first randomized efficacy signal from NATURE, while longer follow-up and any subsequent publication of the complete results will determine how much weight the finding carries in practice.