Resistant Hypertension
True resistant hypertension is defined as blood pressure that remains above target despite concurrent use of three antihypertensive agents of different classes (including a diuretic) at optimal doses.
1. Rule Out Pseudo-Resistance
Before investigating secondary causes, you must exclude factors that mimic resistant hypertension:
- White Coat Effect: Confirm elevated BP with 24-hour Ambulatory BP Monitoring (ABPM) or strict home monitoring.
- Non-adherence: Account for >50% of apparent resistance. Discuss openly without judgment.
- Suboptimal Dosing: Ensure patients are on maximal tolerated doses, not just starter doses.
- Inaccurate Measurement: Wrong cuff size, patient talking, arm unsupported, or no rest period before measurement.
2. Screen for Interfering Substances
Common medications and substances that elevate BP:
- NSAIDs (Ibuprofen, Naproxen, Celecoxib)
- Oral contraceptives
- Sympathomimetics (decongestants like pseudoephedrine, diet pills)
- Excessive alcohol intake (>2 standard drinks/day)
- Recreational drugs (Cocaine, Amphetamines)
- Licorice (contains glycyrrhizin)
3. Workup for Secondary Causes
If true resistance is confirmed, investigate secondary causes (accounting for 10-20% of resistant cases):
| Cause | Clinical Clues | Initial Screening |
|---|---|---|
| Primary Aldosteronism | Hypokalemia (spontaneous or diuretic-induced), muscle weakness | Aldosterone/Renin Ratio (ARR) |
| Obstructive Sleep Apnea | Snoring, daytime somnolence, obesity, morning headaches | STOP-BANG questionnaire, Polysomnography |
| Renal Parenchymal Disease | Elevated creatinine, abnormal urinalysis, nocturia | eGFR, Urinalysis, Renal Ultrasound |
| Renovascular Disease | Abdominal bruit, flash pulmonary edema, acute Cr rise with ACEi/ARB | Doppler US, CTA, or MRA of renal arteries |
4. Pharmacological Escalation (Step 4 Therapy)
Once adherence is confirmed and secondary causes are ruled out or treated, pharmacological escalation is required.
The PATHWAY-2 Trial established that adding an MRA (Mineralocorticoid Receptor Antagonist) is the most effective 4th-line agent for resistant hypertension.
- Step 4: Add Spironolactone (12.5-50 mg/day). Ensure eGFR > 30 and K+ < 4.5 mEq/L before starting. Check U&Es 1-2 weeks after initiation.
- Step 5 (If MRA contraindicated/ineffective): Add Beta-blocker (if HR > 70) OR Alpha-blocker (Doxazosin) OR centrally acting agent (Clonidine).
- Step 6: Direct vasodilator (Hydralazine or Minoxidil) - Usually requires specialist referral due to reflex tachycardia and severe fluid retention (requires concurrent beta-blocker and potent loop diuretic).