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Study Summary

The SPYRAL HTN-OFF MED Pivotal randomized, controlled trial compared the efficacy of renal denervation therapy to a sham procedure in 331 patients (aged 20-80 years) with hypertension (see accompanying Hurst's Central Illustration). To be included in the study, patients had to either not be on any antihypertensive medications, or discontinue any antihypertensive medications 3 weeks before trial enrollment. At the 3-month follow-up, the primary outcome (change in 24-hour systolic ambulatory blood pressure) was -4.7 mmHg in the renal denervation group compared with -0.6 mmHg in the sham control group, for a treatment difference of -4.0 mmHg (95% CI -6.2 to -1.8, P <0.001). The secondary outcome of change in office systolic blood pressure at the 3-month follow-up was -9.2 mmHg in the renal denervation group compared with -2.5 mmHg in the sham group, for a treatment difference of -6.6 mmHg (95% CI -9.6 to -3.5, P <0.001). The treatment effect of renal denervation was similar throughout various subgroups within the trial. There were no major device or procedure-related adverse events in either group.

Commentary

Study Strengths: This was a large, multicenter, randomized, sham-controlled trial designed to assess the efficacy and safety of renal denervation therapy in the absence of antihypertensive medications. The analysis cleverly used a Bayesian study design to combine data from this trial (N = 251) with a previous randomized pilot trial (SPYRAL HTN-OFF MED Pilot, N = 80) which was done under similar enrollment and treatment criteria. This increased the study population to 331 randomly assigned patients, and in turn greatly increased the overall power of the study. Compliance of participants to ensure they were not on any antihypertensive agents was also monitored via urine drug testing.

Study Limitations: The follow-up period was limited to 3 months due to ethical and safety concerns of withholding antihypertensive medications from patients. In fact, previous trials investigating renal denervation therapy have shown an increasing treatment effect between 3 and 6 months, suggesting that the current study may have underestimated the treatment effect in the renal denervation group. The trial excluded patients with a history of recent stable or unstable angina, heart failure, cerebrovascular accident or transient ischemic attack, or atrial fibrillation due to ethical considerations of withholding antihypertensive medications from this population.

Next Steps/Clinical Perspective: The SPYRAL HTN-OFF MED Pivotal trial follows the earlier SYMPLICITY HTN-3 trial, which did not show a significant treatment difference between renal denervation and sham procedure. The SPYRAL HTN-OFF MED trial demonstrated that renal denervation lowers blood pressure in hypertensive patients in the absence of medications, and showed clinically significant reductions in office and ambulatory blood pressure at 3 months, consistent across all subgroups, compared to sham control. There were no major device- or procedure-related adverse safety events reported through 3 months. Long-term safety and efficacy from this trial will be followed up over 3 years. A complimentary randomized clinical trial in patients with uncontrolled hypertension despite antihypertensive therapy (SPYRAL HTN-ON MED) is now enrolling.

Trial References

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Böhm  M, Kario  K, Kandzari  D, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised sham-controlled trial. Lancet. doi:10.1016/S0140-6736(20)30554-7.
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Townsend  RR, Mahfoud  F, Kandzari  DE, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of anti-hypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017;390(10108):2160–2170.

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