BARCELONA, Spain - Monday 1 September 2014: Longer-term follow-up data from the SYMPLICITY HTN-3 trial confirmed both the safety and absence of clinical benefit of renal denervation, according to the 12 month results presented for the first time at ESC Congress today by Professor George L. Bakris, director of the ASH Comprehensive Hypertension Center, The University of Chicago Medicine in Chicago, Illinois.
Professor Bakris said: "The 12 month results presented today are consistent with the six month findings which were previously reported. We found that renal denervation is safe but resulted in blood pressure reductions similar to a sham procedure."
He added: "Renal denervation has been used in patients with hypertension who do not respond to treatment with medication. A catheter is inserted into the kidney via the femoral artery and a device applies radiofrequency pulses to the renal arteries to damage the nerves and in theory reduce blood pressure. SYMPLICITY HTN-3 was the first trial to compare renal denervation to a sham procedure, in which patients received a surgical intervention with no denervation procedure, to account for any placebo effect."
SYMPLICITY HTN-3 included 535 patients with resistant hypertension (office systolic blood pressure [SBP] >160 mmHg) who were prescribed three or more hypertension medications, including a diuretic, from 88 medical centres in the US. Patients were randomised 2:1 to renal denervation or the sham procedure.
Patients and clinicians assessing blood pressure were blinded to the treatment patients received. They were unblinded following assessment of the six month primary endpoint. At this stage control patients could crossover to the renal denervation group if they met treatment criteria and agreed to the procedure. Of the 171 patients randomised to the sham procedure, 101 crossed over at six months and received renal denervation.
The primary efficacy endpoint was the change in office SBP from baseline to six months in the renal denervation arm (353 patients) compared to the sham control arm (171 patients). The secondary endpoint was the change in 24-hour ambulatory SBP at 6 months. The primary safety endpoint was a composite of major adverse events. As previously reported, the trial met its primary safety endpoint but did not meet its primary or secondary efficacy endpoints.(1)
Safety and efficacy data were reported for three groups in the trial: 12 month outcomes for the original renal denervation group, six month outcomes for the crossover group, and 12 month outcomes for the non-crossover group (control subjects who did not meet inclusion criteria, specifically a SBP >160 mmHg, or did not wish to undergo renal denervation). The non-crossover group had a lower baseline SBP
(176.1 mmHg) due to inclusion of subjects with SBP <160 mmHg at six months of follow up and thus can no longer serve as a comparator group for the renal denervation arms.
At 12 month follow-up, office SBP measurements were available for 320 patients in the original renal denervation arm. These patients continued to experience a decrease in office SBP (-18.9 mmHg) which represented an additional 3.6 mmHg decrease in SBP compared to the six month data.
For office BP, the researchers found that the crossover renal denervation group demonstrated a slightly larger decrease in SBP 6 months after the procedure than the original denervation group (-17.7 mmHg [n=92 patients] vs. -15.3 mmHg, respectively).
For 24-hour ambulatory BP, the crossover group experienced a mean reduction of -9.2 mmHg at six months after the procedure (n=82 patients) while the original renal denervation arm had a mean reduction of -7.6 mmHg at 12 months (n=255 patients).
The non-crossover group showed a much larger decrease in office SBP at 6 months (-32.9 mmHg) than any of the other groups, likely due to inclusion in this group of subjects who did not qualify for crossover to renal denervation due to a SBP <160 mmHg at six months. Between 6 and 12 months office SBP increased by 11.5 mmHg, bringing the net decrease in office SBP at 12 months to -21.4 mmHg.
Professor Bakris said: "The large changes in blood pressure reported in the non-crossover group are most likely due to individuals who varied their adherence to antihypertensive medications in these different time points in the trial. However, further research is needed to address the issue of medication adherence when designing these types of trials."
The rate of major adverse events at one year was 6.8% in the original renal denervation group, 6.4% in the crossover renal denervation group, and 7.2% in the non-crossover group. Professor Bakris said: "We did not find any difference in the rate of adverse events between any of the study arms, confirming the safety of the renal denervation procedure."
He concluded: "The latest results of the SYMPLICITY HTN-3 trial show that the renal denervation procedure is safe but reduces blood pressure to a similar extent as a sham procedure. Our findings cast doubt on whether renal denervation, as performed in the SYMPLICITY HTN-3 trial, is useful for lowering blood pressure in patients with resistant hypertension. However, despite these results, further studies using the insights obtained from this and other studies should be conducted using a sham control arm to confirm our results."