Abstract

Introduction: Endothelin-1 causes vasoconstriction by activation of calcium flux in smooth muscle cells. Use of endothelin receptor antagonists (ERAs) has remained controversial. Renal denervation (RD) has also been investigated as a treatment option for resistant hypertension (RHTN). The efficacy of these two novel treatment strategies was compared. Methods: Placebo-controlled and sham-controlled randomized clinical trials testing ERA or RD as treatments for RHTN were selected. Prespecified subgroup analyses comparing the efficacy of ERA and RD were conducted for outcomes of 24-hour (hr) blood pressure (BP) and office BP. Results: Nine studies (3 ERA and 6 RD) were identified that included 1,708 participants (816 ERA and 892 RD). Cochran risk of bias assessment showed 72% of the domains to be low risk of bias for the ERA studies and 88% of the domains to be low risk of bias for the RD studies. The raw mean difference (RMD) between ERA and placebo control was statistically significant for 24-hr systolic (SBP) (-8.34 mmHg; 95% CI -11.51 to -5.81, 24-hr diastolic (DBP) (-6.77 mmHg; 95% CI -8.90 to -4.63), office SBP (-4.50 mmHg; 95% CI -6.92 to -2.08), and office DBP (-2.01 mmHg; 95% CI -2.13 to -1.88). The RMD between RD and sham control was not statistically significant for 24-hr SBP (-1.85 mmHg; 95% CI -3.88 to 0.18), 24-hr DBP (-0.67 mmHg; 95% CI -1.84 to 0.51), office SBP (-1.93 mmHg; 95% CI -5.17 to 1.31), and office DBP (-1.55 mmHg; 95% CI -3.43 to 0.33). The interaction between the treatment subgroups was statistically significant for 24-hr SBP and DBP, but not for office SBP and DBP. Discussion: ERAs had greater reduction in 24-hr and office BP compared to RD among patients with RHTN. Despite efficacy in reducing BP in RHTN, use of ERAs remains controversial given the cost and side effect profile. RD does not reduce BP among patients with RHTN. Medications are the optimal treatment for RHTN and sham controlled data showing efficacy is needed prior to widespread use and adoption of RD in RHTN.

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