Long-term data show blood pressure reductions with renal artery denervation procedure

Introduction and methods

Background

Renal artery denervation may be an alternative for patients with treatment-resistant hypertension who can not achieve durable blood pressure control with medication or whose adherence is challenged by medication intolerance [1].

The SYMPLICITY HTN-3 trial confirmed the safety of a renal artery denervation catheter, but failed to show statistically significant efficacy in reducing either office or 24h SBP at 6 months follow-up compared with the sham control [2,3].

Recent studies [4,5,6] have shown effective and statistically significant short-term blood pressure reductions with newer generation renal artery denervation systems [7,8], which refuels the interest in renal artery denervation for contemporary management of hypertension. Moreover, long-term outcomes of SIMPLICITY HTN-3 may help to understand the durability of effects of renal denervation on blood pressure and the long-term safety of this procedure.

Aim of the study

The study aim was to evaluate the long-term efficacy and safety of renal artery denervation at 36 months follow-up of patients in the SYMPLICITY HTN-3 trial.

Methods

SYMPLICITY HTN-3 was a single-blind, randomized, multicenter, sham-controlled trial. Eligible patients, between 18 and 80 years old, had uncontrolled hypertension with office SBP of ≥160 mmHg, and 24h SBP of ≥135 mmHg, despite being on at least 3 antihypertensive drugs, of which one was a diuretic .

From Sep 29, 2011, to May 6, 2013, 1442 patients were screened. A total of 535 patients were randomized (2:1) to undergo radiofrequency renal denervation (n=364) or a sham control procedure (n=171); patients remained on antihypertensive drugs. At 6 months, patients were unmasked after the primary endpoint assessment, at which point eligible patients in the sham control group who met the inclusion criteria (office SBP ≥160 mm Hg, 24 h SBP ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Efficacy, safety and antihypertensive drug use was followed up to 36 months.

Outcomes

The main endpoint for this analysis was the change in SBP to 36 months for the renal artery denervation group compared with the sham control group. Changes in blood pressure up to 36 months were analyzed in patients in the original renal artery denervation group (n=219), in those who underwent renal artery denervation after 6 months (crossover group; n=63), and those who did not (non-crossover group; n=33). As part of the analysis . For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value.

The safety endpoint included the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalization for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of >70% within 48 months.

Main results

Efficacy

• Patients who had undergone renal artery denervation had significantly lower office SBP at 36 months compared with those in the sham control group; –26.4 mm Hg (SD 25.9) in the renal artery denervation group vs.–5.7 mm Hg (24.4) in the sham control group with an adjusted treatment difference of –22.1 mm Hg (95%CI: –27.2 to –17.0); (P≤0.0001).
• Patients who had undergone renal artery denervation had significantly lower 24h SBP at 36 months compared with those in the sham control group; –15.6 mm Hg (SD 20.8) in the renal artery denervation group vs. –0.3 mm Hg (15.1) in the sham control group with an adjusted treatment difference of –16.5 mm Hg (95%CI: –20.52 to –12.5); (P≤0.0001).
• A post-hoc sensitivity analysis, in which missing measures for all groups were imputed up to 36 months, showed similar findings for SBP and DBP.
• Without imputation, patients who had undergone renal artery denervation had significantly better long-term blood pressure control than those in the sham control group .
• Larger reductions in mean hourly changes in 24 h ambulatory SBP from baseline to 12-month follow-up and baseline to 36-month follow-up were seen in the renal artery denervation group compared to the sham control group.
• Patients in the crossover group had a reduction in BP only after renal artery denervation procedure.
• Without imputation, up to 36 months, 357 (98%) of 364 patients in the renal artery denervation group spent on average 18% (SD 25) of time in the therapeutic blood pressure range compared with 171 (100%) patients in the sham control group who spent an average of 9% (19) of time in the therapeutic blood pressure range (p≤0.0001). Results were similar with imputation.

Safety

• Rates of adverse events were similar across all groups. The rate of the composite safety endpoint to 48 months was 15% (54 of 352 patients) for patients who had undergone renal artery denervation 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group.

Conclusion

References

Find this article online at The Lancet