SAN FRANCISCO—The verdict is in for renal denervation for treatment-resistant hypertension: According to results from major trials at TCT, the therapy produces safe, efficient, and persistent reductions in blood pressure.

First-in-man and post-market results from the REDUCE-HTN study, which investigated the safety and efficacy of the balloon-based Vessix (Boston Scientific) radiofrequency system, showed a significant reduction in mean office-based systolic and diastolic blood pressure (–24/–10.3 mm Hg; p < 0.001) in 139 patients who completed follow-up at 6 months; these effects persisted at 12 months (–29.6/–13.6 mm Hg), although this data includes follow-up from only 41 patients. “There were no acute safety events and a low rate of procedure-related serious adverse events,” presenter Horst Sievert, MD, added. “One patient developed renal artery stenosis, but all of the other safety events were more or less access-related.”

Likewise, 18-month follow-up from the EnligHTN-1 Trial (the first-in-human study of the EnligHTN renal denervation system by St. Jude Medical) showed that the multi-electrode denervation catheter system significantly reduced mean baseline office blood pressure in the 44 patients who completed follow-up (–24/–10 mmHg; p < 0.0001). “At 18 months, approximately two-thirds of patients had achieved an office-based systolic blood pressure of less than 160 mm Hg, therefore attesting to a change in their hypertension classification,” presenter Stephen G. Worthley, PhD, noted. “Importantly, between 12 and 18 months, there have been no new serious device- or procedure-related events.”

Three-year results from SYMPLICITY HTN-2—the longest-term data in a randomized, controlled setting—demonstrated an average blood pressure reduction of –33/–14 mm Hg from baseline. In terms of safety, there were no device-related serious adverse events and no detrimental effects on the renal vasculature following treatment. In his presentation of the data, Robert J. Whitbourn, MBBS, MD, added that these blood pressure reductions did not appear to be related to changes in antihypertensive medications. “If anything,” he said, “there was a reduction in number of medications and dose overall.”

When discussing the results from SYMPLICITY HTN-2 and other renal denervation updates, David Kandzari, MD, also spoke about the efficacy achieved in cross-over patients: “In the cohort that crossed over to renal denervation, for whom 2- year follow-up is available, these patients also seemed to achieve a very effective and sustainable reduction in systolic and diastolic blood pressure measurements, thus reminding us that there’s little reason to withhold such therapies in such hypertensive patients.”

“One of the topical interests for renal denervation therapy, too, is: ‘Could patients come off of their pharmacologic therapies, and could the pharmacologic burden be reduced in some way?’ It’s noteworthy that, while not well-controlled in the context of these studies, there is a fraction of patients who do achieve a dose or number of medication reduction.” However, Dr. Kandzari added, the majority of patients maintain their same medical therapy, and thus the device technology should be considered complementary to medications, rather than as a replacement.

Hypertension and Beyond

While the evidence gap on renal denervation for treatment-resistant hypertension is closing, the scope of possibilities for treating other conditions is growing. Several presentations at TCT examined the other conditions—those characterized by elevated renal sympathetic nerve activity—that could be managed with renal nerve ablation.

• Heart failure: The pathophysiology of heart failure seems to support the rationale for renal denervation. According to Justin E. Davies, MBBS, PhD, early experience in small trials has shown that renal denervation improves cardiac function in patients with resistant hypertension, without introducing new safety events. Studies such as REACH (a sham study looking for symptomatic improvement in heart failure) and SYMPLICITY-HF (a safety study) will provide further insight. “I believe there’s a logical reason why renal denervation may be a useful approach in this area,” he stated, “and it may expand treatment over and above the neurohormonal blockade and other pharmacological therapies available today.”
• Chronic kidney disease: Because patients with chronic kidney disease have inappropriate activation of the sympathetic nervous system, renal denervation may be particularly effective in improving these patients’ difficult-to-treat hypertension—with an added benefit of lessening arterial stiffness—according to C. Venkata S. Ram, MD.
• Glycemic control and diabetes: Diabetes was one of the most common comorbidities of patients in the Global SYMPLICITY Registry, affecting 41.3% of the population. According to research presented by Felix Mahfoud, MD, renal denervation may improve fasting glucose levels, insulin levels, and insulin sensitivity. In one study, renal denervation not only improved blood pressure, but also seemed to slow progression of diabetic status (from glucose intolerance to diabetes), and seven patients (19%) even had a diabetic status regression from glucose intolerance to normal glucose tolerance.

Keywords: Electrodes, Follow-Up Studies, Denervation, Comorbidity, Insulin Resistance, Glucose, Vascular Stiffness, Glucose Intolerance, Registries, Renal Artery Obstruction, Sympathetic Nervous System, Heart Failure, Blood Pressure Determination, Hypertension, Renal Insufficiency, Chronic, Diabetes Mellitus, Fasting

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