Renal Denervation for Moderate Treatment-Resistant Hypertension Explored

San Francisco, CA—Extending renal denervation therapy to patients with moderate treatment-resistant hypertension appears justified because even modest BP reductions are associated with significant attenuation of cardiovascular mortality and morbidity. “The magnitude of BP reduction is less pronounced in patients with moderate hypertension compared with a more severe condition,” said David E. Kandzari, MD, of Piedmont Heart Institute, Atlanta, Ga., at TCT 2013, “but in the context of what has been achieved in pharmaceutical trials, it is still clinically very meaningful.”

Current data suggest that, unlike in patients with more severe hypertension, patients with moderate treatment-resistant hypertension who undergo renal denervation experience a reduction in ambulatory BP that more closely approximates a reduction of office BP. However, the possible compromise of patient safety with an invasive procedure highlights the need to identify predictors of treatment effect. This includes determining whether the procedural risk or the actual cardiovascular risk of moderate hypertension skews the risk/benefit balance of the invasive catheter-based procedure. Kandzari said that such predictors could also be useful in demonstrating the socioeconomic benefits of the therapy in the moderate hypertension population, which includes a potential reduction in medication burden. Kandzari reviewed data from several recent small studies.

In a single-center pilot study of 20 patients with an office systolic BP between 140 and 160 mm Hg on an average of 5.4 antihypertensive medications, office systolic pressure decreased from a mean baseline of 148.4 to 135.3 mm Hg at 6 months, while ambulatory pressure fell from baseline 147 to 135.7 mm Hg over the same time period (both P<.01). 

In another multicenter study of 54 patients with an office-baseline BP of 148.4/79.5, BP was reduced at 6 months by a mean of 13/7 mm Hg (P<.001). In a subgroup of 36 patients with ambulatory pressure measurements, the BP decline was similar (-14/7 mm Hg). Despite study guidance to the contrary, 37% of patients decreased their antihypertensive medications during the first 6 months, while none increased medications. No procedural adverse events were seen. 

Global SYMPLICITY

In the Global SYMPLICITY registry, 26% of 1,097 patients had a systolic BP between 140 and 160 mm Hg. In results reported at the recent European Society of Cardiology Congress, this subgroup showed a 15-point decline in office systolic pressure at 6 months and a 21 mm Hg decrease at 12 months. In a subgroup of patients with ambulatory BP measurements, declines in systolic pressure were considerably smaller (9 and 7 mm Hg, respectively). 

Upcoming clinical trials 

The upcoming proposed global pivotal randomized REDUCE HTN trial will include a small arm of 50 subjects with moderate resistant hypertension, Kandzari said. Additionally, the multicenter blinded, randomized SYMPLICITY HTN 4 trial is currently enrolling patients with an office systolic pressure between 140 and 160 mm Hg and an average 24-hour ambulatory systolic pressure above 135 despite maximum tolerated doses of at least three antihypertensive medications. The primary endpoints of SYMPLICITY HTN 4 are acute safety and reaching a systolic pressure of less than 140 mm Hg, with at least a 5-point reduction in office or ambulatory systolic pressure at 6 months.

Disclosures:

Kandzari reports receiving grant support from Abbott Vascular, Boston Scientific and Medtronic CardioVascular; and consultant fees/honoraria from Abbott Vascular, Boston Scientific, Medtronic CardioVascular, Micell Technologies and Terumo Medical.