SYMPLICITY HTN-3 Update: 12-Month Outcomes Following Unblinding of Subjects at Six Months
Longer-term follow-up data from the SYMPLICITY HTN-3 trial released as part of ESC Congress 2014 confirmed the safety of renal denervation, but continued to show a lack of clinical benefit.
The SYMPLICITY HTN-3 trial 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 centers in the US. Patients were randomized 2:1 to renal denervation or a sham procedure. Previously reported six-month findings, found renal denervation to be safe, but having little to no impact on reducing hypertension. According to Professor George L. Bakris, director of the ASH Comprehensive Hypertension Center at the University of Chicago Medicine, IL, the new 12-month results remain consistent with those at six-months. "We found that renal denervation is safe but resulted in blood pressure reductions similar to a sham procedure," he said.
In the updated trial, patients were unblinded to the treatment they received and patients could crossover to the renal denervation group, provided they met treatment criteria and agreed to the procedure. Of the 171 patients randomized to the sham procedure, 101 crossed over at six months and received renal denervation. 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.
At 12-month follow-up, office SBP measurements, which were available for 320 patients in the original renal denervation arm, continued to show a decrease (-18.9 mmHg). For the crossover renal denervation group, study investigators noted a slightly larger decrease in SBP six 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 group had a mean reduction of -7.6 mmHg at 12 months (n=255 patients). According to Bakris, the non-crossover group showed a much larger decrease in office SBP at six months (-32.9 mmHg) than any of the other groups, likely due to the inclusion of patients who did not qualify for crossover to renal denervation. 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.
Moving forward, Bakris notes that the updated 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. He suggests that further studies are needed using a sham control arm to confirm these results. He also recommends further research to address the issue of medication adherence when designing these types of trials.
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