Does renal denervation require cardiovascular outcome-driven data?

Area of Science:

• Cardiovascular Medicine
• Interventional Cardiology
• Nephrology

Background:

• Hypertension is a global health challenge, driving significant cardiovascular disease.
• Renal denervation (RDN) has emerged as a potential therapy for blood pressure (BP) control.
• Recent trials have evaluated RDN's efficacy and safety, with mixed discussions on outcome measures.

Purpose of the Study:

• To analyze statistical methods in RDN trials regarding endpoint definitions.
• To determine the necessity of major adverse cardiovascular events (MACE)-driven trials versus BP reduction as a surrogate endpoint.
• To provide evidence supporting the use of BP reduction as a valid surrogate for cardiovascular outcomes in RDN research.

Main Methods:

• Systematic review and analysis of statistical methodologies employed in major sham-controlled randomized controlled trials of RDN.
• Evaluation of endpoint definitions, focusing on the comparison between BP reduction and MACE as trial outcomes.
• Statistical assessment of the evidence supporting BP reduction as a surrogate for cardiovascular outcomes.

Main Results:

• Most sham-controlled RDN trials demonstrate a significant reduction in 24-hour/daytime ambulatory systolic BP compared to control groups.
• Analysis of statistical methods supports the conclusion that RDN significantly reduces blood pressure versus sham controls.
• The use of BP reduction as a surrogate endpoint is supported by trial data and practical limitations of MACE-driven trials.

Conclusions:

• RDN is a proven method for significantly reducing blood pressure in hypertensive patients.
• Blood pressure reduction serves as a sufficient surrogate endpoint in RDN trials, simplifying outcome assessment.
• Considering BP as a surrogate endpoint offers advantages for future hypertension research and treatment strategies, especially given the challenges of long-term MACE evaluation.