Renal Denervation May Prove Helpful for Patients With Resistant Hypertension

The importance of blood pressure control in reducing risk of cardiovascular disease (CVD) is well-established. However, a large proportion of individuals do not reach their blood pressure goal, and many are labeled as having “resistant hypertension,” or persistent elevation >130/80, despite adherence to 3 or more different drug classes at optimal doses, including at least 1 diuretic medicine.¹ Dr. Keith Ferdinand took the stage during the American Society of Preventive Cardiology 2023 Congress on CVD Prevention to address misconceptions around resistant hypertension and discuss the potential application of renal denervation (RDN) in this setting.

Under-treatment was identified as the main contributor to “resistant hypertension” (over nonadherence to medication).² For those patients who are on optimal therapies, what options exist? RDN involves ablation of the afferent artery adventitia to limit central sympathetic outflow and of the efferent artery to limit vasoconstriction within the kidney, in addition to promoting cardiometabolic changes such as limiting renin release.³ It presents a nonpharmacological solution by addressing the role of sympathetic nervous system hyperactivity in hypertension.

RDN seemed like a promising therapy until the randomized sham-control trial SYMPLICITY HTN-3 in 2014, which demonstrated an insignificant change in blood pressure between the treatment and sham arms.⁴ This lack of significance may be explained by design flaws with the catheter itself or overtreatment of the sham/control arm despite the intent for both arms to maintain the same medications throughout the trial. Results may also have been confounded by the Hawthorne effect if patients began taking their “baseline” medications when enrolled in the clinical trial.⁵ Finally, the 6-month follow-up in SYMPLICITY HTN-3 may have been inadequate, as patients followed 12 to 36 months after RDN demonstrated significant reductions in blood pressure, with increasing magnitude over time.⁶

Studies on RDN, including the use of radiofrequency and ultrasound waves in the afferent and efferent renal arteries, are ongoing and hopeful. While clear indications for RDN are lacking, its application may prove helpful for patients with true resistant hypertension or those who wish to limit pill burden or cannot tolerate long-term medications at the necessary doses.⁷

As the development of RDN continues, ensuring equitable access is essential. “It may be the unintended consequence that, if the devices have a benefit and there are barriers to access, it widens disparities,” Dr. Ferdinand noted. “We should make sure any new device is applied across all populations regardless of sex, gender, race, ethnicity, socioeconomic status, geography, ability, or disability.”

Dr. Claire Cambron is a chief resident at the Oregon Health & Science University and served as a CardioNerds Conference Scholar during the American Society of Preventive Cardiology 2023 Congress on CVD Prevention.

References

1. Denker MG, DL Cohen. Resistant hypertension and renal nerve denervation. Methodist Debakey Cardiovasc J. 2015;(4):240-244. doi:10.14797/mdcj-11-4-240
2. Carey RM, Calhoun DA, Bakris GL, et al. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension. 2018. doi:10.1161/HYP.0000000000000084
3. Mahfoud F, Schlaich MP, Lobo MD. Device therapy of hypertension. Circ Res. 2021;128(7):1080-1099. doi:10.1161/CIRCRESAHA.121.318091
4. Krum H, Schlaich MP, Sobotka PA, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2014;383(9917):622-629. doi:10.1016/S0140-6736(13)62192-3
5. Kjeldsen SE, Fadl Elmula FEM, Persu A, Jin Y, Staessen JA. Renal sympathetic denervation in the aftermath of Symplicity HTN-3. Blood Press. 2014;23(5):256-261. doi:10.3109/08037051.2014.953861
6. Bhatt DL, Vaduganathan M, Kandzari DE, et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 trial. Lancet. 2022;400(10361):1405-1416. doi:10.1016/S0140-6736(22)01787-1
7. Barbato E, Azizi M, Schmieder RE, et al. Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2023;44(15):1313-1330. doi:10.1093/eurheartj/ehad054