Expand Management of Blood Pressure With Renal Denervation in Patients Undergoing Staged PCI for Advanced Coronary Artery diseasE

Expand Management of Blood Pressure With Renal Denervation in Patients Undergoing Staged PCI for Advanced Coronary Artery Disease

EMBRACE is a randomized, controlled, multicenter clinical study evaluating the effect of renal denervation on clinical adverse events in hypertensive patients undergoing staged percutaneous coronary intervention (PCI) for multivessel coronary artery disease.

Hypertension remains one of the most important modifiable risk factors for cardiovascular morbidity and mortality worldwide. Despite the availability of multiple antihypertensive drug classes and evidence based treatment strategies, a substantial proportion of patients continue to have inadequately controlled blood pressure. Poor blood pressure control is particularly common among patients with multivessel coronary artery disease and is associated with increased adverse cardiovascular outcomes, including myocardial infarction, stroke, heart failure, progression of renal dysfunction, and increased mortality.

Renal sympathetic nerve activity plays a central role in the pathophysiology of hypertension through modulation of renal blood flow, sodium and water retention, renin release, and systemic sympathetic tone. Renal denervation is a catheter based procedure designed to disrupt renal sympathetic afferent and efferent nerves by delivering energy to the renal artery wall. Multiple randomized clinical studies have demonstrated that renal denervation can reduce blood pressure in patients with uncontrolled hypertension, with sustained effects during follow up and an acceptable safety profile when performed using contemporary devices and techniques.

Patients with multivessel coronary artery disease undergoing percutaneous coronary intervention represent a particularly relevant population in which blood pressure control is of critical importance. In many cases, coronary revascularization is performed as a staged procedure, with an initial index PCI followed by a planned staged PCI to complete revascularization of remaining significant coronary lesions. This staged approach allows for optimization of patient safety and procedural efficiency, particularly in patients with complex coronary anatomy or a high ischemic burden.

The EMBRACE study is designed to evaluate the benefit of renal denervation in improving clinical outcomes in patients with multivessel coronary artery disease undergoing staged percutaneous coronary intervention. This study is a prospective, randomized, controlled, multicenter clinical investigation. Eligible patients are adults with multivessel coronary artery disease undergoing staged PCI who have hypertension defined as persistent elevation of office systolic blood pressure despite treatment with two or more antihypertensive medications. Following confirmation of eligibility and completion of the index PCI, patients who remain eligible prior to the planned staged PCI are randomized in a 1:1 allocation ratio to receive renal denervation in addition to standard care or standard care alone.

Renal denervation is performed using a commercially available catheter based renal denervation system in accordance with the manufacturer's instructions for use. The procedure is carried out via standard endovascular access and is performed either during the staged PCI procedure or as a standalone catheter based intervention, depending on procedural planning and investigator judgment. All patients continue to receive guideline directed medical therapy for hypertension and coronary artery disease throughout the study.

Patients randomized to the control group undergo staged PCI and continue standard medical therapy without renal denervation. Antihypertensive medications are managed according to routine clinical practice, with adjustments permitted at the discretion of the treating physician to ensure patient safety and appropriate blood pressure control.

The primary objective of the EMBRACE study is to assess the effect of renal denervation on clinically meaningful cardiovascular outcomes in this high-risk population. The primary endpoint is a hierarchical composite endpoint analyzed using a win-ratio methodology, comparing patients randomized to renal denervation versus standard care. This hierarchical clinical outcome framework allows prioritization of more severe and clinically relevant events over less severe outcomes, providing an integrated assessment of net clinical benefit. The hierarchical outcome includes major adverse cardiovascular and cerebrovascular events such as death and other serious cardiovascular outcomes, followed by additional clinically relevant events as defined in the study protocol.

Secondary objectives of the EMBRACE study include evaluation of blood pressure control, changes in antihypertensive medication burden, renal safety, and procedure-related safety outcomes. Blood pressure measurements are obtained using standardized office blood pressure assessment methods at baseline and predefined follow-up intervals. Changes in blood pressure and medication use are evaluated as secondary and supportive endpoints, providing mechanistic context for observed clinical effects.

Safety endpoints include assessment of renal artery-related complications, access-site complications, renal function changes, and other adverse events related to renal denervation and percutaneous coronary intervention. Clinical events are collected throughout the follow-up period to allow comprehensive evaluation of both efficacy and safety.

The EMBRACE study is conducted in accordance with the principles of the Declaration of Helsinki, Good Clinical Practice guidelines, and applicable regulatory requirements. Written informed consent is obtained from all participants prior to performance of any study specific procedures. Study oversight is provided through standardized monitoring and safety reporting mechanisms to ensure data integrity and participant safety.

By integrating renal denervation into the staged PCI care pathway, EMBRACE seeks to address an important unmet clinical need in patients with advanced coronary artery disease and uncontrolled hypertension. The study aims to provide clinical evidence regarding the safety and effectiveness of renal denervation in this population and to clarify the potential role of this intervention as an adjunct to contemporary revascularization and pharmacologic treatment strategies.

The results of EMBRACE may inform future treatment approaches for patients with multivessel coronary artery disease and persistent hypertension, a population at particularly high risk for adverse cardiovascular outcomes. If renal denervation demonstrates meaningful and durable blood pressure reduction without compromising procedural safety, it may represent an important therapeutic option to optimize cardiovascular risk reduction in these patients.

List of abbreviation:

PCI - Percutaneous Coronary Intervention SoC - Standard of Care MACCE - Major Adverse Cardiovascular and Cerebrovascular Events MACE - Major Adverse Cardiovascular Events

Inclusion Criteria:

• Subject with multi-vessel disease
• Having successful index PCI and planned staged procedure within 1-6 weeks to complete revascularization
• Subjects ≥21 years of age
• Office systolic blood pressure at index procedure and/or staged procedure (systolic blood pressure >140 mmHg) while taking 2 or more antihypertensive drugs
• Subject agrees to have all study procedures performed, and is competent and willing to provide written, informed consent to participate in this clinical study prior to staged procedure

Exclusion Criteria:

• - Contraindication for RDN outlined by IFU
• Acute MI at time of the staged PCI procedure (AMI at time of the index PCI is allowed)
• Subject has undergone prior renal denervation.
• Subject has renal artery anatomy that is ineligible for RDN treatment per Symplicity Spyral™ IFU
• Known secondary cause (e.g., renal artery stenosis, primary aldosteronism, pheochromocytoma, Cushing's syndrome, or other identifiable etiologies).
• Severe renal failure (eGFR <30 ml/min/1.73 m²)
• Known LVEF <30%
• Known history of polycystic kidney disease, unilateral kidney, or undergone renal transplant
• Mechanical circulatory support during PCI
• Subject is under judicial protection, tutorship or curatorship
• Failure of index procedure
• Acute MI, severe renal failure, need for mechanical circulatory support, or legal incapacity between the index and staged procedures resulting in loss of eligibility.