Renal denervation: The most advanced and efficacious interventional approach to treat hypertension

Konstantinos Tsioufis

Following the release of the European Society of Hypertension’s (ESH’s) updated position paper on renal denervation, Konstantinos Tsioufis, professor of Cardiology at the University of Athens, Athens, Greece and immediate past president of ESH, discusses the use of renal denervation in the treatment of hypertension, considers the latest evidence in favour of the approach, and outlines the questions still to be answered.

What are the advantages of using renal denervation to treat hypertension?

In all recent sham-controlled trials there were clinically favourable effects of renal denervation for treatment of uncontrolled hypertension. The great advantage is that the intervention has shown meaningful office and ambulatory blood pressure decrease across multiple phenotypes of patients with mild to moderate as well as more severe hypertension in the presence and absence of medication. This constant reduction in blood pressure over 24 hours—the “always on” impact—of renal denervation differentiates the intervention-induced changes in blood pressure from those by drugs due to the diverse pharmokinetic profiles and dosing regiments along with patient non-adherence.

How does renal denervation compare to other treatment approaches that are available?

According to latest second generation randomised controlled trials and the Global SYMPLICITY Registry (GSR), average blood pressure reduction induced by renal denervation compared to sham ablation is 8-10mmHg in office systolic blood pressure reading and 5-7mmHg in ambulatory systolic blood pressure readings. Other interventional approaches to modulate sympathetic tone by baroreceptor activation is still under investigation.

What do trial data tell us about this approach and its outcomes in the long-term?

The antihypertensive effect of renal denervation is durable and taking into consideration the average drop of 10mmHg in office blood pressure, the renal denervation effect can be translated to significant improved cardiovascular prognosis (approximately 20% reduction in cardiovascular events and 26% in stroke). Renal denervation is also an early and late-term safe procedure with minimal complications based on data from registries and recent sham randomised controlled trials. The observed blood pressure reduction caused by renal denervation is maintained long term with data available up to three years after the procedure.

Are there any unanswered questions to be investigated?

Currently there is an urgent need to define predictors of blood pressure response post renal denervation and there are efforts focusing on diverse parameters both clinical and laboratory. There are data showing that in untreated patients with higher baseline heart rate and plasma renin aldosterone levels renal denervation are associated with better blood pressure reduction. Moreover, the average and standard deviation of night-time ambulatory blood pressure has been identified as a potential robust predictor, which requires further research. Another question is the long-term durability of blood pressure lowering and safety beyond three years as well as safety and efficacy in patients with comorbidities such as renal failure. Further studies are also needed on the renal denervation-induced clinical impact in patients with heart failure, atrial fibrillation and increased overall cardiovascular risk. The cost-effectiveness of the procedure for the health systems is an additional point to be addressed.

Are there any drawbacks to this approach?

Given the established efficacy and safety the only drawback for renal denervation is physicians’ inertia to consider and refer hypertensives for this approach. Additionally, there is a lack of information on the clinical impact of neuromodulation from the stand point of hypertensive patients that limits the implication of the technology to everyday practice.

How should physicians evaluate which patients are suitable for renal denervation treatment for hypertension?

According to the latest evidence, the criteria for considering hypertensive patients for renal denervation is persistent uncontrolled hypertension despite guideline-based therapy including ameliorated lifestyle measures and efforts to increase adherence. Heightened cardiovascular risk (i.e. evident organ damage) or established disease (i.e. coronary artery disease, heart failure) might be pointing towards treatment priority with renal denervation in hypertension. Additionally, patients who are unable or unwilling to take medication might be another renal denervation group, especially in the first stages of the hypertensive disease. The shared decision making process is mostly important for renal denervation and according to patients’ preferences this interventional approach could be selected for diverse phenotypes of hypertension.

Do you see renal denervation as having a significant role to play in the future treatment of hypertension?

Renal denervation constitutes today the most advanced and efficacious device-based interventional approach to treat hypertension, expanding therapeutic options as an alternative and not as a competitive strategy. This would be of important clinical value since approximately half of individuals with hypertension do not meet guideline-directed blood pressure goals. Based on the available evidence, renal denervation is definitely included in the individualised treatment strategy of the future for better hypertension control and reduction of overall cardiovascular disease burden.


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