Resistant hypertension and renal denervation: Who’s kidding whom?

Abstract

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the homeostasis of blood pressure regulation. Its role in the pathophysiology of hypertension is, however, complex. Over-activation of the RAAS in severe and accelerated phase hypertension is generally recognised but its role in drug-resistant hypertension less clear. This is one question being addressed by the British Hypertension Society PATHWAY Trial Programme (www. bhsoc.org).The interrelationships between the RAAS and the sympathetic nervous system are also complex and extend from the central nervous system to the periphery, including post-ganglionic nerve endings, the adrenal gland and the kidney. It was therefore of considerable interest to note the impressive blood pressure reduction observed in early studies of renal denervation (RDN) in patients with apparent drug-resistant hypertension and observe to what extent neurohumoral changes accompanied the falls in blood pressure.By way of background, resistant hypertension is defined as blood pressure remaining above goal in spite of the concurrent use of three antihypertensive agents of different classes. Ideally one of these agents should be a diuretic, and all agents should be prescribed at optimal doses. Its true prevalence is unknown, but observational studies and clinical trials suggest that it is a common clinical problem. In an analysis of National Health and Nutrition Examination Survey (NHANES), 1 of participants being treated for hypertension only 53% were controlled to a blood pressure <140/90 mmHg. In those with diabetes or chronic kidney disease the percentage controlled was considerably less. Similar figures (63%) for all treated patients have recently been reported by the Health Survey for England 2 but, of course, many of the participants in these surveys were not receiving optimal treatment for their hypertension.Resistant hypertension comprises a heterogeneous group of patients including those with undiagnosed secondary hypertension, inaccurate blood pressure measurement, white coat hypertension and poor adherence with prescribed medication. In the author's experience true resistant hypertension is uncommon. Thus, in the evaluation of patients with apparent resistant hypertension, a comprehensive management algorithm should be applied which includes investigations to rule out secondary causes, confirmation of appropriate treatment (drugs and doses), including a trial of spironolactone, and formal assessment of drug compliance. This should include observed drug ingestion in the clinic followed by blood pressure monitoring for up to 4 hours and 24 hour ambulatory blood pressure monitoring thereafter. The post-dosing period of observation for 4 hours in the clinic is a precaution for cases where substantial falls in blood pressure occur in the hitherto non-compliant or poorly compliant patient. If the facility is available, urinary drug assays provide additional information on non-compliance.Only after the diligent exclusion of the majority of patients referred with so...

A Perspective on the Delivery of Renal Denervation Therapy Based on Pre-Clinical Data

“…Post hoc evaluation of the data has furthered these discussions and provided important insights. Hypotheses range from selection criteria of hypertensive enrollees as “resistant to medication” (3) and the Hawthorne effect (4) , to catheter design (5) , operator inexperience, insufficient amount of therapy delivery (6) , and/or imprecise location of delivery, among others. Regardless, the impact of the SYMPLICITY HTN-3 trial was notorious and immediate.…”

Renal denervation: An uncertain future

“…It is now more than 5 years since I wrote my first commentary on renal denervation (RDN). 1 At the time, I was prompted by the contrast between the enormous enthusiasm for the technique, inspired by dramatic claims of >30 mmHg reductions in systolic blood pressure (SBP) observed in patients with resistant hypertension who had undergone RDN, [2][3][4] and the minimal falls in blood pressure (BP) when RDN was studied in well-controlled trials, particularly those involving sham-control procedures. [5][6][7] National bodies and international guidelines followed, 8,9 which recommended a moratorium on the widespread clinical uptake of RDN until such time as the true benefits or otherwise of RDN had been evaluated in well-controlled studies, in a variety of patient subgroups with hypertension and possibly other cardiovascular conditions, including heart failure.…”