In the face of growing clinical adoption of renal denervation in Europe and elsewhere outside the United States, the European Society of Cardiology (ESC) and the European Association of Percutaneous Cardiovascular Interventions have issued a consensus document summarizing the evidence for the percutaneous procedure and providing guidance on appropriate use.

Written by an expert panel led by Felix Mahfoud, MD, of Saarland University Hospital (Homburg, Germany), the document was published online April 25, 2013, ahead of print in the European Heart Journal.

According to the ESC statement, evidence from clinical studies, primarily the 2 Symplicity trials (HTN-1 and HTN-2), “strongly supports” the idea that catheter-based radiofrequency ablation of afferent and efferent renal nerves reduces blood pressure and improves blood pressure control in patients with drug-treated resistant hypertension. The effect has been shown to last at least 36 months, with an average decline in systolic pressure of 33 mm Hg from baseline and in diastolic pressure of 19 mm Hg from baseline.

In a press release, Dr. Mahfoud said, “The hope is that insurance companies and health-care providers will read [this statement] and will only pay for those centers and especially for those patients who fit the criteria published in the paper. The problem right now is that there are no European criteria for determining which patients are most likely to benefit and which centers have the necessary experience.”

Defining the Right Candidates

Echoing the protocol in the Symplicity trials, the statement recommends that potential candidates for renal denervation should meet the following criteria:

• Have an office-based systolic pressure of at least 160 mm Hg, or at least 150 mm Hg in the presence of type 2 diabetes
• Be treated with at least 3 antihypertensive drugs of different types in adequate doses, including 1 diuretic; addition of a mineralocorticoid receptor antagonist such as spironolactone may also be considered
• Comply with healthy lifestyle modifications
• Be free of pseudoresistance (eg, ‘white coat’ hypertension) as confirmed by ambulatory blood pressure monitoring (average blood pressure > 130 mm Hg or mean daytime blood pressure > 135 mm Hg)
• Have been systematically assessed to exclude causes of secondary hypertension such as renal artery stenosis, pheochromocytoma, sleep apnea syndrome, and primary hyperaldosteronism
• Have preserved renal function (GFR ≥ 45 mL/min/1.73 m²)
• Have eligible renal arteries, characterized by absence of polar or accessory arteries, stenosis, or prior revascularization

To rule out potentially curable forms of hypertension—for which renal denervation is not effective—patients should be carefully screened by centers specializing in the management of hypertension, with at least 1 hypertension expert directly involved in the process.

To minimize complications, the statement also recommends that denervation be performed only by interventional cardiologists or other vascular specialists who have been trained in the procedure and are qualified to manage potential complications. Appropriate expertise, the authors say, can be assumed in centers performing at least 25 renal interventions a year. Moreover, centers should enter their data into large registries to ensure proper quality control and allow for analysis of procedural success and long-term follow-up.

Recent analysis suggests that although renal denervation entails increased upfront costs (for hospitalization, catheters, and operators), the predicted reductions in cardiovascular events and a 1.3-year increase in median survival render the procedure cost-effective in the long run. However, the authors caution, this assessment is sensitive to varying costs in different health-care systems.

Different Approaches in Europe, United States

In a telephone interview with TCTMD, Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), observed that while renal denervation is investigational in the United States, in Europe physicians are “already doing a fair number of procedures” and at least 5 technologies have CE mark approval.

“In that context, there might have been a feeling that [the ESC] should put out an official document essentially saying that it is okay to be performing these procedures in the absence of a large definitive trial or an ironclad dataset,” he said. Dr. Bhatt is co-principal investigator of the pivotal Symplicity HTN-3 trial aimed at  approval of renal denervation in the United States.

At the same time, Dr. Bhatt noted, some procedures may be performed for indications that go beyond the evidence—eg, in hypertensive patients who are not truly resistant but simply do not want to take medications. “That may be a logical application of this technology, but it hasn’t been studied,” he said. “So maybe this document was also an attempt to address [such practices].”

Dr. Bhatt compared the different approaches being taken in Europe and the United States to those adopted in the development of TAVR. Unlike European regulators, the US Food and Drug Administration (FDA) first required a large definitive trial to prove that TAVR technology is safe and effective. The downside of that policy is that it delays the availability of medical advances to patients in need; the upside is that it protects patients from being exposed to a potentially unsafe procedure and spares the healthcare system the cost of a potentially ineffective technology, he explained. “I think the FDA’s cautious approach is a wise one because once you unleash a technology, it’s hard to put the genie back in the bottle,” Dr. Bhatt said.

Cardiologists Capable of Screening

As for the patient selection criteria laid out in the consensus document, Dr. Bhatt said they are similar to those for most trials of therapies for resistant hypertension. “I think they define a population that is most likely to benefit from renal denervation,” he added.

While agreeing with the authors about the importance of screening candidates for secondary hypertension, Dr. Bhatt said it need not be done by a separate hypertension expert since cardiologists receive adequate training in that regard.

Dr. Bhatt was less convinced by the requirement that centers should perform at least 25 procedures annually, since it is unclear how much center or operator volume matters to the outcome. “I do worry a little about volume standards because it’s always possible to meet them by doing more procedures that don’t fit the inclusion criteria,” he commented. “So [setting a threshold] can have unintended consequences.”

However, he added, operators should have good peripheral interventional skills. “People who have not done renal angiography or intervention should not be doing this procedure,” he said. On the other hand, for those with such experience, “technically the leap to doing renal intervention isn’t that great.”

Overall, the ESC statement provides “useful guidance to anyone anywhere in the world who’s doing renal denervation,” Dr. Bhatt concluded. “I would urge them, if they’re going to be doing denervation anyway, to at least follow the wisdom in this document instead of just being cavalier.”

Related Stories:

• Symplicity Works: Renal Denervation Reduces Resistant Hypertension
• More Data Needed on Renal Denervation
• Model Suggests Renal Denervation Cost-effective for Resistant Hypertension