What is the role of renal denervation in treating resistant hypertension?

Renal Denervation for Resistant Hypertension

Renal denervation may be considered for resistant hypertension patients with uncontrolled blood pressure despite optimal three-drug therapy, but only when performed at medium-to-high volume centers after a shared risk-benefit discussion and multidisciplinary assessment. 1

Definition and Diagnosis of Resistant Hypertension

Resistant hypertension is defined as:

• Blood pressure that remains above target despite concurrent use of ≥3 antihypertensive agents of different classes (including a diuretic) at optimal doses, OR
• Blood pressure that requires ≥4 antihypertensive drugs to achieve control 1, 2

Before considering renal denervation, it's essential to:

1. Confirm true resistant hypertension by excluding pseudoresistance:

   • Poor BP measurement technique
   • White coat effect
   • Medication nonadherence
   • Suboptimal medication choices or dosing 3

2. Screen for secondary causes of hypertension:

   • Primary aldosteronism (~20% of resistant hypertension cases)
   • Chronic kidney disease
   • Renal artery stenosis
   • Obstructive sleep apnea
   • Pheochromocytoma 3, 4

Pharmacological Management (First-Line Approach)

The recommended treatment algorithm for resistant hypertension is:

1. Optimize lifestyle modifications:

   • Sodium restriction
   • Weight loss if overweight/obese
   • Regular physical activity
   • DASH diet
   • Alcohol limitation 1, 3

2. Optimize three-drug combination therapy:

   • ACE inhibitor or ARB
   • Long-acting calcium channel blocker
   • Thiazide-like diuretic (preferably chlorthalidone rather than hydrochlorothiazide) 1, 3

3. Add fourth-line agent:

   • Spironolactone 25-50 mg daily (first choice) if eGFR >45 mL/min/1.73m² and K+ <4.5 mmol/L 1, 3
   • If spironolactone is not tolerated, consider:
     • Eplerenone
     • Higher dose thiazide/thiazide-like diuretic
     • Loop diuretic (if eGFR <30 mL/min/1.73m²)
     • Beta-blocker (preferably bisoprolol)
     • Alpha-blocker (doxazosin)
     • Centrally acting agent 1

Role of Renal Denervation

According to the 2024 ESC Guidelines for the management of hypertension:

1. When to consider renal denervation:

   • For patients with resistant hypertension uncontrolled despite a three BP-lowering drug combination
   • For patients with increased CVD risk and uncontrolled hypertension on fewer than three drugs
   • Only after a shared risk-benefit discussion and multidisciplinary assessment
   • Only if performed at medium-to-high volume centers 1

2. When NOT to use renal denervation:

   • As a first-line BP-lowering intervention
   • In patients with moderately to severely impaired renal function (eGFR <40 mL/min/1.73m²)
   • In patients with secondary causes of hypertension 1

3. Evidence limitations:

   • Lack of adequately powered outcomes trials demonstrating safety and cardiovascular benefits
   • The SYMPLICITY HTN-3 trial failed to show significant difference between renal denervation and sham procedure in reducing systolic BP 1
   • Most studies have limited long-term follow-up data 5

Clinical Decision-Making Algorithm

1. Confirm resistant hypertension:

   • Verify BP measurements (office and 24-hour ambulatory)
   • Assess medication adherence
   • Rule out white coat hypertension

2. Optimize pharmacological therapy:

   • Ensure optimal three-drug combination (ACE/ARB + CCB + thiazide-like diuretic)
   • Add spironolactone as fourth agent if appropriate
   • Consider alternative fourth agents if spironolactone is contraindicated or not tolerated

3. Consider renal denervation if:

   • BP remains uncontrolled despite optimal medical therapy
   • Patient has been evaluated by a multidisciplinary team
   • Patient understands the risks and benefits
   • Procedure can be performed at a medium-to-high volume center
   • Patient has normal to mildly impaired renal function (eGFR ≥40 mL/min/1.73m²)
   • Secondary causes of hypertension have been ruled out

Caveats and Pitfalls

• Therapeutic inertia: Don't delay intensification of treatment when BP remains uncontrolled 3
• Medication adherence: Poor adherence is a common cause of apparent resistant hypertension 2
• Diuretic optimization: Ensure appropriate diuretic selection (chlorthalidone preferred over hydrochlorothiazide; loop diuretics for eGFR <30) 3
• Monitoring: Close monitoring of electrolytes is essential when using multiple agents, especially with spironolactone 3
• Ethnic considerations: In Black patients, initial treatment should include a CCB and/or thiazide diuretic 1, 3

Renal denervation remains a promising but not fully validated approach for resistant hypertension. It should be reserved for carefully selected patients after optimization of medical therapy and thorough evaluation by a multidisciplinary team.