WASHINGTON – Renal denervation may have struck out as antihypertensive therapy in the sham-controlled SYMPLICITY HTN-3 trial reported in March at the American College of Cardiology’s annual meeting, but an independent report at the same meeting from a worldwide renal denervation registry showed that the vast majority of patients who’ve undergone with renal denervation recently were nothing like the patients enrolled in the failed trial.

In fact, patients who met enrollment criteria for the SYMPLICITY HTN-3 trial constituted a bare 8% of "real world" patients treated with renal denervation, based on results from the first 1,000 patients enrolled in the Global SYMPLICITY Registry, said Dr. Michael Böhm, professor and chairman of cardiology at Saarland University Hospital in Homburg/Saar, Germany.

Out of the 751 patients of the first 1,000 in the registry with data available on their office systolic blood pressure 6 months after treatment, 62 patients (8%) fulfilled the entry criteria of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial by having an office systolic pressure of at least 160 mm Hg, a systolic pressure of at least 135 mm Hg by ambulatory blood pressure monitoring, and on treatment at maximally tolerated dosages with at least three different classes of antihypertensive medications (N. Engl. J. Med. 2014;370:1393-1401).

This low level of patients with clinically confirmed, resistant hypertension occurred against a backdrop in which a scant majority of registry patients even had severe hypertension, let alone a medically uncontrolled form. Among the 751 patients with 6-month follow-up blood pressure data, 433 (58%) received renal denervation with an office systolic blood pressure at baseline of at least 160 mm Hg, said Dr. Böhm.

"SYMPLICITY HTN-3 covered only a few percent of patients" who undergo renal denervation, he said. "The goal of the registry is to include a broad population, including patients without hypertension but other conditions associated with overactivity of the sympathetic nervous system" such as arrhythmia or heart failure.

Among the 433 patients with an office systolic blood pressure of at least 160 mm Hg – the minimum level of hypertension to warrant routine treatment by renal denervation according to several current policies – 244 (56%) were at this high pressure despite treatment with at least three classes of antihypertensive drugs. In this more clearly drug-resistant group, office systolic pressure fell by an average 20.2 mm Hg at 6 months after renal denervation. But only 62 patients on at least three types of drugs were also at maximally tolerated dosages of these drugs, another key element in defining drug resistance. Patients on maximally tolerated dosages represented only a quarter of all patients on multiple drugs in the Registry, and just 14% of the 433 patients with severe hypertension.

Among the 62 patients who matched the SYMPLICITY HTN-3 enrollment criteria, the average drop in office, systolic blood pressure at 6 months after treatment was 17.3 mm Hg, not too different from the average drop of 14.1 mm Hg seen in the renal denervation arm of SYMPLICITY HTN-3, Dr. Böhm noted.

The registry results showed that in patients with an office systolic pressure of less than 160 mm Hg, renal denervation was lousy at blood pressure reduction. Among the 222 patients who had pretreatment systolic pressures of 140-159 mm Hg and 6-month follow-up, office systolic blood pressure dropped by an average of 4.6 mm Hg. The procedure was even less effective in the 96 registry patients with an office systolic pressure of less than 140 mm Hg prior to treatment. In this subgroup systolic pressures averaged a 14.2-mm Hg increase 6 months after treatment.

"The only significant interaction between blood pressure lowering and no lowering was blood pressure at baseline," Dr. Böhm said. He gave no details on how many patients in the registry underwent renal denervation to treat hypertension and how many for other reasons.

The Global SYMPLICITY Register involves more than 200 centers in many European countries as well as in Canada, Australia, Korea, and elsewhere. A large number of registry centers are in Germany, and many centers there and elsewhere participated in the first two SYMPLICITY HTN trials. Participating centers entered the registry based on their experience with renal denervation and had to have performed at least 30 procedures prior to entry into the registry. The 6-month data also showed that renal denervation was "very safe," with "very low" rates of adverse events, Dr. Böhm said.

The Global SYMPLICITY Registry is sponsored by Medtronic, the company that markets Symplicity renal denervation devices. Dr, Böhm said that he has served on an advisory board to, been a speaker for, and received research support from Medtronic as well as from several other drug and device companies.

mzoler@frontlinemedcom.com

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Registry renal denervation skews from resistant hypertension