# 🔧 Resistant HTN & Device Therapy

## 🚀 Breakthrough 2025 Integration

**Renal denervation receives formal Class 2b recommendation** marking the first device-based therapy integration in AHA/ACC hypertension guidelines. This represents a paradigm shift toward interventional management of resistant hypertension.

### 🔍 Resistant Hypertension: Systematic Evaluation

#### 📋 Definition: Resistant Hypertension

Blood pressure remains above goal despite **3 optimally-dosed antihypertensives** from different classes, including a **diuretic**, OR controlled on **≥4 medications**

1

#### Confirm True Resistance

**Out-of-office BP monitoring:** ABPM or HBPM to exclude white-coat effect

**Medication review:** Verify optimal dosing, appropriate combinations, patient adherence

2

#### Assess Adherence

**Pharmacy records:** Prescription filling patterns, timing analysis

**Drug levels:** When available, direct measurement of medication concentrations

3

#### Screen for Secondary Causes

**Primary aldosteronism:** Universal screening with ARR (Class 1 recommendation)

**Other causes:** Sleep apnea, renal artery stenosis, pheochromocytoma evaluation

4

#### Optimize Medical Therapy

**Fourth-line agent:** Spironolactone 12.5-50 mg daily (Class 1 recommendation)

**Alternative agents:** Amiloride, eplerenone, or other evidence-based combinations

5

#### Consider Device Therapy

**Renal denervation:** Class 2b recommendation for selected patients

**Multidisciplinary evaluation:** Required before procedural intervention

## 💊 Advanced Treatment Strategies

#### 🧪 Spironolactone: Fourth-Line Therapy Class 1

##### 📊 Efficacy in Resistant HTN (PATHWAY-2)

- **BP Reduction:** −8.7 mmHg home systolic vs placebo (95% CI −9.7 to −7.7)
- **Best-of-four ranking:** Spironolactone most effective of 4 add-on drugs in approximately 58% of patients in crossover
- **Optimal Dose:** 12.5-50 mg daily (titrate based on response/tolerance)
- **Source:** Williams B et al. *Lancet* 2015;386(10008):2059-2068. PMID 26414968

###### ✅ Ideal Candidates:

- eGFR ≥45 mL/min/1.73m²
- Potassium \<4.5 mEq/L
- No significant kidney disease
- Volume-dependent resistant HTN

###### ⚠️ Monitoring Protocol:

Check electrolytes and creatinine at 1 week, 1 month, then quarterly. Watch for hyperkalemia (\>5.5 mEq/L) and acute kidney injury.

#### 🔧 Renal Denervation Class 2b

##### 📈 Contemporary Evidence

- **Office BP:** 5-10 mmHg systolic reduction
- **24-hour ABPM:** 3-8 mmHg reduction
- **Response Rate:** 60-70% show clinically meaningful reduction
- **Durability:** Effects maintained at 3 years

###### 🎯 Patient Selection Criteria:

- Office SBP 140-180 mmHg despite treatment
- Documented medication adherence
- eGFR ≥40 mL/min/1.73m²
- Suitable renal artery anatomy
- Life expectancy \>1 year

###### ❌ Contraindications:

- Significant renovascular abnormalities
- Previous renal artery intervention
- Type 1 diabetes with neuropathy
- eGFR \<40 mL/min/1.73m²

#### ⚗️ Alternative Combination Strategies

###### 🔄 When Spironolactone Intolerant:

- **Amiloride:** 5-10 mg daily (K+-sparing, less hormonal effects)
- **Eplerenone:** 25-100 mg daily (selective MR antagonist)
- **Beta-blockers:** Carvedilol, bisoprolol if not contraindicated
- **Alpha-blockers:** Doxazosin XL for volume-independent resistance

###### 🧬 Novel Agents (Research):

- **Finerenone:** Non-steroidal MR antagonist
- **SGLT2 inhibitors:** Modest BP effects + cardiorenal protection
- **GLP-1 agonists:** 3-5 mmHg reduction + weight loss

### 🔬 Renal Denervation: Comprehensive Overview

#### 🔬 Mechanism of Action

- **Sympathetic nerve ablation:** Disrupts renal afferent/efferent pathways
- **Central effects:** Reduces overall sympathetic tone
- **Local renal effects:** Decreases renin release, sodium retention
- **Vascular effects:** Improved endothelial function

#### ⚕️ Procedure Details

- **Approach:** Percutaneous, femoral artery access
- **Technology:** Radiofrequency or ultrasound ablation
- **Duration:** 45-90 minutes outpatient procedure
- **Recovery:** Same-day discharge, minimal downtime

#### 📊 Key Clinical Trial Data

##### SPYRAL HTN-OFF MED Pivotal

**24-h ABPM:** -3.9 mmHg SBP vs sham (95% CrI -6.2 to -1.6)\
**Office SBP:** -6.5 mmHg vs sham\
*Bohm 2020 Lancet, PMID 32234534*

##### SPYRAL HTN-ON MED

**24-h ABPM:** -7.4 mmHg SBP vs sham (95% CI -12.5 to -2.3)\
**Office SBP:** -6.8 mmHg vs sham\
*Kandzari 2018 Lancet, PMID 29803589*

##### RADIANCE-HTN SOLO

**Daytime ABPM:** -6.3 mmHg baseline-adjusted SBP difference (95% CI -9.4 to -3.1)\
**Office SBP:** approximately -6.5 mmHg between-group\
*Azizi 2018 Lancet, PMID 29803590*

### 👥 Multidisciplinary Team Evaluation (Class 1 Requirement)

#### 🩺 Hypertension Specialist

- Confirm true resistance
- Optimize medical therapy
- Exclude secondary causes
- Long-term BP management

#### 🫀 Interventional Cardiologist

- Assess procedural feasibility
- Evaluate renal artery anatomy
- Perform procedure if appropriate
- Manage complications

#### 🧠 Clinical Psychologist

- Assess adherence barriers
- Evaluate decision-making capacity
- Support lifestyle modifications
- Manage treatment expectations

#### 💊 Clinical Pharmacist

- Medication reconciliation
- Drug interaction screening
- Adherence optimization
- Cost-effective alternatives

#### 🤝 Shared Decision-Making Considerations

##### ✅ Potential Benefits

- Modest but clinically meaningful BP reduction
- Potential medication reduction
- No systemic drug effects
- Durable effects at 3+ years
- Improved quality of life scores

##### ⚠️ Limitations & Risks

- 30-40% non-response rate
- Continued medication requirement
- Procedural costs and access
- Potential need for repeat procedures
- Limited long-term outcome data

## 📊 Treatment Evidence Summary

| Treatment | Class/Level | BP Reduction | Response Rate | Key Considerations |
|----|----|----|----|----|
| **Spironolactone** | Class 1 | −8.7 mmHg home SBP vs placebo (PATHWAY-2) | Best-of-4 in approximately 58% (crossover) | Monitor K+, creatinine; eGFR ≥45 required |
| **Amiloride** | Class 2a | 10-15 mmHg | 50-60% | Alternative if spironolactone intolerant |
| **Renal Denervation** | Class 2b | 5-10 mmHg | 60-70% | Multidisciplinary evaluation required |
| **Beta-blockers** | Class 2b | 8-12 mmHg | 40-50% | Carvedilol preferred; avoid if contraindicated |
| **Alpha-blockers** | Class 2b | 6-10 mmHg | 40-50% | Doxazosin XL; monitor orthostatic hypotension |

## 📚 Sources

1.  **Williams B, MacDonald TM, Morant S, et al; British Hypertension Society's PATHWAY Studies Group.** Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2). *Lancet.* 2015;386(10008):2059-2068. [PMID: 26414968](https://pubmed.ncbi.nlm.nih.gov/26414968/).
2.  **Bhatt DL, Kandzari DE, O'Neill WW, et al; SYMPLICITY HTN-3 Investigators.** A controlled trial of renal denervation for resistant hypertension. *N Engl J Med.* 2014;370(15):1393-1401. [PMID: 24678939](https://pubmed.ncbi.nlm.nih.gov/24678939/).
3.  **Böhm M, Kario K, Kandzari DE, et al; SPYRAL HTN-OFF MED Pivotal Investigators.** Efficacy of catheter-based renal denervation in the absence of antihypertensive medications. *Lancet.* 2020;395(10234):1444-1451. [PMID: 32234534](https://pubmed.ncbi.nlm.nih.gov/32234534/).
4.  **Kandzari DE, Böhm M, Mahfoud F, et al; SPYRAL HTN-ON MED.** Effect of renal denervation on blood pressure in the presence of antihypertensive drugs. *Lancet.* 2018;391(10137):2346-2355. [PMID: 29803589](https://pubmed.ncbi.nlm.nih.gov/29803589/).
5.  **Azizi M, Schmieder RE, Mahfoud F, et al; RADIANCE-HTN SOLO.** Endovascular ultrasound renal denervation to treat hypertension. *Lancet.* 2018;391(10137):2335-2345. [PMID: 29803590](https://pubmed.ncbi.nlm.nih.gov/29803590/).
6.  **Carey RM, Calhoun DA, Bakris GL, et al; American Heart Association.** Resistant Hypertension: Detection, Evaluation, and Management. *Hypertension.* 2018;72(5):e53-e90. [PMID: 30354828](https://pubmed.ncbi.nlm.nih.gov/30354828/).
7.  **Brown C, Clark D, Jones DW.** Updates in the 2025 AHA/ACC Hypertension Guideline. *Curr Hypertens Rep.* 2026;28(1). [PMID: 41843050](https://pubmed.ncbi.nlm.nih.gov/41843050/). \[Source for: 2025 update — RDN as adjunctive option in select resistant-HTN patients.\]

### 🎯 Resistant HTN & Device Therapy: Key Learning Points

#### 🔍 Systematic Evaluation

- Confirm resistance with out-of-office monitoring
- Assess adherence through pharmacy records
- Universal primary aldosteronism screening
- Optimize medical therapy before devices

#### 💊 Medical Optimization

- Spironolactone is Class 1 fourth-line therapy
- −8.7 mmHg additional home SBP vs placebo (PATHWAY-2, PMID 26414968) — set patient expectations accordingly
- Monitor electrolytes and renal function
- Alternative agents for intolerance

#### 🔧 Device Therapy

- Renal denervation: modest but durable effects
- Multidisciplinary evaluation mandatory
- 30-40% non-response rate expected
- Continued medications still required

📚 For Educational Purposes Only

© 2025 University of Dubuque PA Program - All Rights Reserved


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