Exploring Potential Referral Pathways for Renal Artery Denervation and Developing a Centre of Excellence in Ireland.

Arterial hypertension is one of the most significant and prevalent risk factors for cardiovascular disease. Despite widespread awareness of the condition, as well as a multitude of available antihypertensive drug classes, rates of uncontrolled hypertension remain high on a global scale. Frequently, poor compliance with anti-hypertensive medication plays a big role in patients' inability to attain adequate blood pressure control. In individuals with resistant and/or uncontrolled hypertension, renal denervation is an emerging device-based therapy that has shown to be efficacious and safe in reducing blood pressure in several sham controlled trials. Additionally, it represents a treatment option for patients intolerant to oral pharmacotherapy. University Hospital Galway has been performing renal denervation procedures over the past number of years within multicentre, international sham-controlled trials and registries. Representing a novel and emerging antihypertensive treatment option, sources of referral for renal denervation are diverse and multiple; thus, there is an unmet need for standardised referral structures in Ireland. Herein, we review current and developing referral pathways for renal denervation at our institution, and discuss streamlined patient management and requirements to establish a centre of excellence.

Does renal denervation require cardiovascular outcome-driven data?

Hypertension is a major driver of cardiovascular disease with a prevalence of 32-34% in adults worldwide. This poses a formidable unmet challenge for healthcare systems, highlighting the need for enhanced treatment strategies. Since 2017, eight major sham-controlled randomised controlled trials have examined the effectiveness and safety of renal denervation (RDN) as therapy for BP control. Although most trials demonstrated a reduction in systolic 24-hour/daytime ambulatory BP compared to control groups, open to discussion is whether major adverse cardiovascular events (MACE)-driven RDN trials are necessary or whether the proof of BP reduction as a surrogate for better cardiovascular outcomes is sufficient. We conducted an analysis of the statistical methods used in various trials to assess endpoint definitions and determine the necessity for MACE-driven outcome data. Such comprehensive analysis provides further evidence to confidently conclude that RDN significantly reduces blood pressure compared to sham controls. Importantly, this enables the interpolation of RDN trial endpoints with other studies that report on outcome data, such as pharmacological trials which demonstrate a significant reduction in MACE risk with a decrease in BP. Moreover, limitations associated with directly evaluating outcome data further support the use of BP as a surrogate endpoint. For example, conducting lengthier trials with larger numbers of participants to ensure robust statistical power presents a substantial challenge to evaluating outcome data. Thus, in light of the crucial need to tackle hypertension, there are notable advantages of considering BP as a surrogate for outcome data.

The Diastolic Blood Pressure J-Curve in Hypertension Management: Links and Risk for Cardiovascular Disease.

PURPOSE OF REVIEW: The treatment of hypertension has changed dramatically over the last century, with recent trials informing clinical guidelines that recommend aiming for lower blood pressure (BP) targets than ever before. However, a "J"- or "U-shaped curve" in the association between diastolic BP and cardiovascular events has been observed in epidemiological studies, suggesting that both high diastolic BPs and diastolic BPs below a certain nadir are associated with higher risk of cardiovascular disease (CVD) events. Despite the potential for confounding and reverse causation, this association may caution against overly intensive BP lowering in some hypertensive adults who also have a low baseline diastolic BP. RECENT FINDINGS: Recent post-hoc analyses of the landmark Systolic Blood Pressure Intervention Trial (SPRINT) appear to contradict these J-curve concerns, finding that the benefit of more intensive BP treatment did not differ based on baseline blood pressure. Similarly, sensitivity analyses of The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) randomized controlled trial found that patients experienced similar benefits from an intensive BP goal, regardless of whether their diastolic BP was above or below 60 mm Hg. Finally, several Mendelian randomization analyses, which are less susceptible to confounding and reverse causation, demonstrated a clear linear relationship between diastolic BP and cardiovascular events. These studies indicate that a potential reduction in CVD risk is possible, irrespective of baseline diastolic BP values. SUMMARY: Sufficient recent evidence indicates that low diastolic BP is not causal of worse cardiovascular outcomes but rather represents confounding or reverse causation. Therefore, while low diastolic BP can be considered a marker of CVD risk, this risk is not expected to increase with further BP lowering when necessary to control concomitant elevations of systolic BP. Indeed, BP reduction in this setting appears beneficial.