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CLINICAL STATEMENTS AND GUIDELINES September 16, 2025 Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 e176 5.6 Resistant Hypertension and Renal Denervation Recommendations for Resistant Hypertension and Renal Denervation Referenced studies that support the recommendations are summarized in the Evidence Table. COR LOE Recommendations Resistant Hypertension 1 B-NR 1 In adults with resistant hypertension, a more detailed evaluation for secondary causes, to include careful review of all medications and removal of those with interfering effects on BP, is beneficial for lowering BP and simplifying treatment.1–5 1 B-R 2 In adults with uncontrolled resistant hypertension despite optimal treatment with first-line antihyperten sive therapy (ie, a combination of ACEi or ARB plus CCB and thiazide-like diuretic [chlorthalidone or inda pamide] and with an eGFR of ≥45 mL/min/1.73 m2), addition of a MRA is recommended to control BP.6,7 2a B-NR 3 In adults with uncontrolled resistant hypertension who cannot tolerate or have contraindications to MRA, the addition of one of the following agents or classes— amiloride, BBs, alpha-blockers, central sympatholytic drugs, dual endothelin receptor antagonists, or direct vasodilators—is reasonable to control BP. 8–11 Renal Denervation 2b B-R 4 In carefully selected patients with systolic and diastolic hypertension (office SBP 140-180 mm Hg and DBP ≥90 mm Hg) and eGFR ≥40 mL/ min/1.73 m2 who have resistant hypertension despite optimal treatment, or intolerable side effects to additional antihypertensive drug therapy, renal denervation (RDN) may be reasonable as an adjunct treatment to BP medications and lifestyle modification to reduce BP.12–14 1 B-NR 5 All patients with hypertension who are being considered for RDN should be evaluated by a multidisciplinary team with expertise in resistant hypertension and RDN.12–14 1 C-EO 6 For patients with hypertension for whom RDN is contemplated, the benefits of lowering BP and potential procedural risks compared with continuing medical therapy should be discussed as part of a shared decision-making process to ensure patients choose the therapy that meets their expectations. Synopsis Resistant hypertension is defined as BP above goal despite treatment with 3 antihypertensive medications with complementary mechanisms of action, including a diuretic at maximally tolerated doses or BP at goal but requiring ≥4 medications (Figure 8).15 Based on the current BP goal of <130/80 mm Hg, the prevalence of resistant hypertension is approximately 8.5% to 20% among hypertensive US adults.16–18 Multiple cohort studies have identified common risk factors for resistant hypertension, including older age, obesity, CKD, and diabetes.15,19 Resistant hypertension is more common in Black populations, which may be related to adverse social factors, including living in a professional shortage area or disadvantaged neighborhood and clinical iner tia.20 Patients with resistant hypertension are known to have at least a 50% higher risk of MI, stroke, end-stage kidney disease, and cardiovascular death than adults with hypertension without resistance to treatment.21–23 Evaluation of resistant hypertension requires exclusion of pseudoresistance, including inaccurate BP measure ment (Section 3.1.3, “Out-of-Office BP Monitoring”), use of interfering medications (Section 5.2.6, “Medica tion Interactions”), white-coat hypertension via out-ofoffice BP monitoring (Sections 3.1.3, “Out-of-Office BP Monitoring,” and 3.2.2, “White-Coat Hypertension and Masked Hypertension, and White-Coat Effect and Masked Uncontrolled Hypertension”), and medication nonadherence (Section 5.2.5, “Antihypertensive Medi cation Adherence Strategies”). Routine measurement of out-of-office BP is an important component of re sistant hypertension management as both home BP and 24-hour ABPM are shown to be superior to office BP in predicting cardiovascular events.24,25 Screening for secondary hypertension (Section 3.2.3, “Secondary Forms of Hypertension”) should be performed because, depending on the specific cause, these conditions re quire a distinct management strategy. RDN is an additional option to consider in managing resistant hypertension. In the absence of antihyperten sive medications, RDN induced a reduction in 24-hour or daytime ambulatory SBP by 4 to 6 mm Hg during a follow-up duration of 2 to 3 months.26–28 In the pres Table 24. Diagnostic Criteria for Preeclampsia Blood pressure SBP ≥140 mm Hg or DBP ≥90 mm Hg on 2 occa sions at least 4 h apart after 20 wks of gestation in a woman with previously normal BP or SBP ≥160 mm Hg or DBP ≥110 mm Hg (severe hypertension can be confirmed within a short interval [min] to facilitate timely antihypertensive therapy). AND Proteinuria ≥300 mg per 24-h urine collection (or this amount extrapolated from a timed collection) or Protein/ creatinine ratio ≥0.3 or Dipstick reading of 2+ (used only if other quantitative methods are not available) OR in the Absence of Proteinuria, New Onset Hypertension With the New Onset of Any of the Following: Thrombocytopenia: Platelet count <100 × 109/L Renal insufficiency: Serum creatinine concentrations >1.1 mg/dL or a dou bling of serum creatinine concentration in the absence of other renal disease Impaired liver function: Elevated blood concentration of liver transaminases to twice normal concentration Pulmonary edema New-onset headache unresponsive to medication and not accounted for by the alternative diagnoses or visual symptoms Reprinted with permission from American College of Obstetricians and Gynecologists.10 Copyright 2020 American College of Obstetricians and Gynecologists. BP indicates blood pressure; DBP, diastolic blood pressure; and SBP, systolic blood pressure. Recommendations for Resistant Hypertension and Renal Denervation (Continued) COR LOE Recommendations Downloaded from http://ahajournals.org by on October 7, 2026