Renal denervation in treatment-resistant hypertension: the need for restraint and more and better evidence

Abstract

The Symplicity studies suggest that intravascular renal sympathetic nervous denervation improves blood pressure in patients with resistant hypertension, thus potentially opening a market for devices to be used when conventional drug therapy fails to restore blood pressure control. However, the size and durability of the antihypertensive, renal and sympatholytic effects of renal denervation, the long-term safety, improvement of quality of life, the possibility to relax antihypertensive drug treatment, the cost-effectiveness, and long-term hard cardiovascular-renal outcomes still remain to be firmly established. Most ongoing studies are small, industry-driven and purely observational with objectives to test new catheters and source of energy for renal nerve ablation or to search for ancillary benefits and new indications of the technique. The most urgent need, that is adequately powered randomized clinical trials testing renal denervation versus usual medical therapy delivered according to the state-of-the-art are under-represented and seldom funded by industry. The authors make a plea for a coordinated research effort in Europe. With this objective, they established collaboration with leading European experts and started the European Network for Coordinating Research on Renal Denervation. In the meantime, renal denervation should remain the ultima ratio in adherent and truly resistant patients with severe hypertension, confirmed by ambulatory monitoring, in whom secondary hypertension has been excluded and in whom all other efforts to reduce blood pressure have failed.

Eligibility for Renal Denervation

“…It entails a 25-to 30-mm Hg decrease in office systolic blood pressure, 84% of patients achieving a decrease in office systolic blood pressure of ≥10 mm Hg with a rate of procedural adverse events <5% assessed 6 months after RDN. 4 However, as reviewed elsewhere, 6,7 blood pressure decrease observed after RDN is highly variable 8 and probably much less than previously thought, especially when ambulatory blood pressure monitoring is used. [8][9][10] Furthermore, stenosis 11,12 and damage 13 of the renal arteries can occur after RDN, and the long-term effect of RDN on renal function is still unclear.…”

“…5,14,15 Hence, until more and better evidence is available, RDN should remain the last resort in patients with truly resistant hypertension. 6,7 Accordingly, several national and international consensus papers 16,17 have proposed guidelines for evaluation and management of patients with resistant hypertension before considering RDN. The proportion of patients with truly resistant hypertension eligible for RDN and the reasons of noneligibility after thorough screening and optimization of drug treatment in expert centers remain elusive.…”

Residual Effect of Renal Denervation in Patients With Truly Resistant Hypertension

“…[15][16][17] In one study, 17 individual blood pressure changes between baseline and 6 months ( Figure) confirm the high variability of office blood pressure responses and absence of mean change in ambulatory blood pressure. As suggested by Fadl Elmula et al, 13 the more convincing results observed in the SYMPLICITY studies 1,2 and subsequent observational studies 8 may be explained by improved drug compliance after renal denervation, but also placebo and Hawthorne effects and regression to the mean. 4 What would have been the blood pressure outcome of the numerous small studies looking for the benefits of renal denervation, should the thorough screening procedure of Fadl This paper was sent to David Calhoun, Guest editor, for review by expert referees, editorial decision, and final disposition.…”

“…These conditions include white-coat hypertension, 5 poor adherence, 6 suboptimal drug treatment, undiagnosed secondary hypertension, 3 and isolated systolic hypertension in the elderly, a highly prevalent and difficult to treat form of hypertension driven by arterial stiffening rather than enhanced sympathetic drive. 7 Neither the SYMPLICITY studies nor most nonrandomized observational reports published subsequently 8 implemented a systematic strategy for differentiating between truly resistant hypertension and conditions that might benefit from an alternative approach, such as addressing the specific cause of the blood pressure elevation or optimizing lifestyle, drug treatment, or adherence.…”

Renal Denervation: Unde Venis et Quo Vadis?

“…In addition to the blood pressure reduction, an improvement of the hyperinsulinism and insulin resistance present in metabolic syndrome seems to occur: 3 months after renal denervation the fasting glucose level (118 ± 3.4 vs. 108 ± 3.8 mg/dL), the insulin level (20.8 ± 3.0 vs. 9.3 ± 2.5 μIU/mL) and the (calculated HOMA) insulin resistance decreased significantly [59]. However, these study populations were relatively small collective and not fully randomized [59,60]. Also a decrease of left ventricular hypertrophy (decrease in left ventricular mass index 6.3 ± 2.2 to 9.6 ± 1.9 g/m 2.7 ) and an improvement in the left ventricular diastolic function were described [61] even though this study also has methodological weaknesses (including a lack of data regarding changes in antihypertensive medication in the follow-up period, echocardiography instead of the gold standard of cardiac MRI for determining the left ventricular mass) [62].…”