Global SYMPLICITY Registry Still Shows Positive Results for Renal Denervation

WASHINGTON, DC—On the heels of the presentation of the negative SYMPLICITY HTN-3 trial showing no efficacy of renal denervation over placebo, the results of a large registry study show significant reductions in both office and ambulatory blood pressure at 6 months in patients with uncontrolled hypertension. Findings from the Global SYMPLICITY registry were presented March 30, 2013, at the American College of Cardiology/i2 Scientific Session.

A team led by Michael Bӧhm, MD, of Universitӓtskliniken des Saarlandes (Homburg/Saar, Germany), enrolled 1,000 patients with uncontrolled hypertension who were treated with the Symplicity Catheter System (Medtronic, Mountain View, CA) at 231 international sites in 37 countries.

At 6 months follow-up, office BP and ambulatory BP were available in 76.6% and 49.1% of patients, respectively. Renal denervation proved safe at 6 months with low rates of cardiovascular death (0.2%), stroke (0.9%), hospitalization for new onset heart failure (0.7%) or A-fib (0.9%), hypertensive crisis/emergency (1.0%), and MI (0.6%). Rates of major adverse events were comparable among the overall population (0.8%), patients in the overall population who met the inclusion criteria for SYMPLICITY HTN-3 (1.3%), and the treatment arm of the SYMPLICITY HTN-3 trial (1.4%).

Overall, patients experienced significant reductions in office BP at 3 and 6 months. However, when broken into subgroups, those with low baseline BP actually saw an increase over time (table 1).

Table 1. Change in Office Systolic BP from Baseline

 

 

3 Months

6 Months

P Value

All Patients
< 140 mm Hg
140-159 mm Hg
≥ 160 mm HG

-10.0
12.9
-2.0
-18.9

-11.9
14.2
-4.6
-21.4

< 0.001a
< 0.001a
0.0006b
< 0.001a

a For both 3 and 6 month change from baseline.
b For 6 months. P = 0.14 at 3 months.

In patients fulfilling the inclusion criteria of HTN-3 (office BP ≥ 160 mm Hg/ambulatory BP ≥ 135 mm Hg), there was a 20.2 mm Hg reduction in office blood pressure at 6 months. Similarly, the office blood pressure reduction among those patients who were also taking at least 3 anti-hypertensive medications at maximally tolerated doses was 17.3 mm Hg. “So in comparison to HTN-3, there was a slightly more pronounced blood pressure reduction,” Dr. Bӧhm observed, adding that the reductions for the trial’s treatment and placebo arms were 14.1 mm Hg and 11.7 mm Hg, respectively.

Ambulatory blood pressure was reduced by 7.9 mm Hg overall at 6 months. In patients fulfilling the inclusion criteria for HTN-3, there was a 9.1 mm Hg reduction, and a 10.3 mm Hg reduction among those patients who were also taking at least 3 anti-hypertensive medications at maximally tolerated doses. Reductions were lower in the HTN-3 treatment and placebo groups at 6.8 mm Hg and 4.8 mm Hg, respectively.

Ultimately, half of the registry population who met inclusion criteria for HTN-3 reported greater than 20 mm Hg reductions in mean office blood pressure at 6 months; 68% reported greater than 10 mm Hg reductions and 77% reported greater than 5 mm Hg reductions.

“There is an excellent safety in the registry,” Dr. Bӧhm said. “The difference between [the study and HTN-3] might be blinding, sham operation, and drug treatment, but despite these limitations, further blinded control studies are necessary to compare the effect in real life.”

Compliance the Key to Improvement

Ronald G. Victor, MD, of Cedars Sinai Medical Center (Los Angeles, CA), questioned whether patients in the registry changed medications over the study period, adding that adjusting medications might be more effective than denervation. He also asked about the baseline differences between responders and nonresponders.

Dr. Bӧhm replied that there were changes in medications, “but the number of medications did not significantly reduce [blood pressure].” What has yet to be evaluated, he continued, is whether or not changing full combinations of medications might lead to better outcomes.

“The significant interaction between response and nonresponse was blood pressure at baseline,” Dr. Bӧhm explained. “There was no independent predictor of nonresponse in these 1,000 patients.”

In addition, George Bakris, MD, of the University of Chicago Medical Center (Chicago, IL), said the key to solving this issue lies in increasing compliance. “Diuretic use was about 25% less in the registry than in the real world. I know people hate diuretics so a lot of people don’t take them,” he observed.

Dr. Bakris also questioned the appropriateness of the exact locations where the denervation occurred in the registry, as “the number of denervations was also on average a little more than usual.”

Dr. Bӧhm explained that the site of denervations changed throughout the study. The classic stance was to denervate at the proximal and ostial nerve, but “at that part of the renal artery, the nerves are quite distant . . . and not as easy to access. Meanwhile we have changed to go more toward the periphery.”

Study Details

Average patient age was 60.7 years and 61.2% were male. About half (50.5%) had a history of cardiac disease and one-quarter (24.6%) had 3 or more comorbidities. Most (78.9%) were on beta-blockers, diuretics (78.2%) and either ACE inhibitors (33.8%) or angiotensin-receptor blockers (67.3%).

On average, 2.2 ± 0.5 renal arteries were treated per patient with a mean length of 41.5 ± 13.1 mm. Each patient received on average 13.5 ± 4.1 bilateral ablations and 127.6 ± 81.1 cc of contrast volume.


Source:Bӧhm M. The global SYMPLICITY registry: safety and effectiveness of renal artery denervation in real world patients with uncontrolled hypertension. Presented at: American College of Cardiology/i2 Scientific Session; March 30, 2013; Washington, DC.

 

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Disclosures
  • The Global SYMPLCITY registry was sponsored by Medtronic.
  • Dr. Bӧhm reports receiving study support and speaker fees from and serving on the advisory boards of several pharmaceutical and device manufacturers.

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