SYMPLICITY HTN-3: Renal Denervation Still Safe, Not Effective at 1 Year

BARCELONA, Spain—One-year results from the SYMPLICITY HTN-3 trial—which followed the unblinding of all patients and the crossover of most control patients at 6 months—confirmed both the lack of a difference in blood pressure reduction across groups and the safety of the procedure, according to a presentation made on September 1, 2014, at the European Society of Cardiology Congress. A worsening of blood pressure after 6 months in the control patients who remained on medical therapy throughout the year was attributed to changes in adherence. 

Methods
The main results of SYMPLICITY HTN-3 were presented in March at the American College of Cardiology/i2 Scientific Session and showed that blood pressure was lowered by a similar amount through 6 months in the patients who underwent renal denervation with the Symplicity Catheter System (n = 364; Medtronic; Mountain View, CA) and those who underwent a sham procedure (n = 171).

At 6 months, patients in the sham-control group were offered renal denervation, but only if they still met the initial inclusion criteria for the trial; 101 ultimately underwent the procedure (crossover group) and the other 70 did not (non-crossover group). George Bakris, MD, of University of Chicago Medicine (Chicago, IL), presented 12-month results from those 2 groups in addition to the patients who were originally randomized to renal denervation. 

 

Results Consistent in All Groups at 1 Year 

Through 12 months, there was no difference between the 3 groups in the rate of the composite safety endpoint (death, new-onset end-stage renal disease, embolic events resulting in end-organ damage, vascular complications, renal artery reintervention, and hypertensive emergency/crisis): 6.8% in the original renal denervation group, 5.3% in the crossover group, and 7.2% in the non-crossover group.

Also at 1 year, patients in all 3 groups had lower office and ambulatory blood pressures compared with baseline (though the reduction in the 24-hour ambulatory readings was not significant in the non-crossover patients). There were no significant differences among the groups (table 1). 

Table 1. Average Blood Pressure Reduction at 1 Year

 

Renal Denervation

Crossovera

Non-Crossover

Office, mm Hg

    Systolic

    Diastolic

 

18.9

7.8

 

17.7

7.1

 

21.4

8.2

24-Hour, mm Hg

    Systolic

    Diastolic

 

7.6

4.7

 

9.2

4.9

 

6.1b

2.9b

aBaseline is the time of the procedure at 6 months; bP = NS for change from baseline.

 

But despite the lack of significant between-group differences at 1 year, there appeared to be variation in the change in blood pressure from 6 to 12 months. In the renal denervation and crossover groups, the reductions seen at 6 months were maintained or strengthened through 12 months, whereas the reductions shrank in the non-crossover patients after the trial was unblinded at 6 months.

Psychology—Not Biology—Likely At Play 

Responding to a question about whether that discrepancy indicates that renal denervation improves the durability of blood pressure reductions, Dr. Bakris said it is probably more a reflection of changes in health behavior—specifically, adherence to medication—after the unblinding of the trial. He noted that comparisons among the 3 groups are confounded by the fact that the non-crossover patients did not qualify—or did not choose to undergo—renal denervation.

“This is well beyond physiology and gets into psychology in terms of adherence and issues related to quality of health and maintenance of health over a long period of time,” he said at a press conference, adding that the procedure might help patients remain motivated to follow their treatment regimens. 

In comments following Dr. Bakris’ presentation, Michael Böhm, MD, PhD, of Saarland University Hospital (Homburg/Saar, Germany), agreed that the trends seen between 6 and 12 months likely indicate changing patient behaviors, pointing out that the strict medication control implemented during the trial cannot be maintained over the long term.

Also, Dr. Böhm said, the trial shows that renal denervation has a similar effect whether it is performed under a blinded condition or in an open-label fashion, pointing to the similar reductions in blood pressure in the original renal denervation group and the crossover patients. 

Renal Denervation Still Kicking

Dr. Bakris said that multiple issues arising from the failure of the SYMPLICITY HTN-3 trial are being actively investigated: population studied, drug prescription changes, variable adherence to therapy, and variations in how the procedure was performed. In addition, he said, researchers have learned that the anatomy of renal nerves is more complex than thought, suggesting that denervation needs to be performed on all branches of the renal artery to get the best effect. 

All of that work is being done to find a way forward for the field of renal denervation. “I would say this is a work in progress,” Dr. Bakris said. “It’s definitely not dead. In fact, I would say it’s out of the ICU now and probably out on the floor.”

   

Sources:
Bakris G. SYMPLICITY HTN-3: 12-month outcomes following unblinding of subjects at 6 months.
Presented at: European Society of Cardiology Congress; September 1, 2014; Barcelona, Spain.

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Disclosures
  • Medtronic funded SYMPLICITY HTN-3.

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