Hypertension, Resistant or Refractory

KEY FEATURES

ESSENTIALS OF DIAGNOSIS

• Blood pressure > 140/90 mm Hg in patients adhering to a triple-drug regimen (including a diuretic) at near-maximal doses

GENERAL CONSIDERATIONS

• Resistant or refractory hypertension is usually due to patient factors, such as:

  • – Excessive sodium, alcohol, and calories

  • – Noncompliance with medications

• Occasionally, the patient ingests other substances that interfere with the effectiveness of treatment, such as:

  • – Nonsteroidal anti-inflammatory drugs

  • – Oral contraceptives

• Another common problem is underdosing of medications, especially diuretics

CLINICAL PRESENTATION

SYMPTOMS AND SIGNS

• Patient may report being under increased stress

• Nonspecific symptoms such as headaches, nose bleeds, fatigue, dyspnea

PHYSICAL EXAM FINDINGS

• Elevated blood pressure

• Evidence of left ventricular hypertrophy such as a precordial lift or fourth heart sound

DIFFERENTIAL DIAGNOSIS

• Inaccurate blood pressure measurement (eg, cuff too small)

• Stimulant exposure (eg, nasal sprays, diet pills, alcohol)

• Aggravating medical conditions (eg, sleep apnea)

• Secondary hypertension (eg, renal artery stenosis)

• Medication noncompliance

DIAGNOSTIC EVALUATION

ELECTROCARDIOGRAPHY

• ECG findings: left ventricular and atrial hypertrophy

DIAGNOSTIC PROCEDURES

• Ambulatory blood pressure monitoring: to confirm resistance and document temporal trends in relation to medication ingestion

TREATMENT

CARDIOLOGY REFERRAL

• Suspected cardiac disease

• Refractory hypertension

HOSPITALIZATION CRITERIA

• Severe hypertension (> 220/120 mm Hg)

• Heart failure

• Stroke

• Myocardial infarction

• Aortic dissection

• Renal failure

MEDICATIONS

• Maximize medications, especially diuretics

  • – If estimated glomerular filtration rate (GFR) is > 50 mL/min/1.73 m², use a thiazide diuretic (eg, chlorthalidone)

  • – If GFR is 30–40 mL/min/1.73 m² or less, use a loop diuretic (eg, furosemide)

• Use the most efficacious combinations of drugs first (eg, a diuretic, an angiotensin-converting enzyme inhibitor, and a calcium channel blocker)

• Spironolactone 12.5–25 mg/day added to the above is often quite effective

• Then consider adding a beta blocker or a central alpha₂-receptor agonist, such as clonidine, or a combined adrenergic inhibitor such as labetalol

• If the resting heart rate is > 70 bpm, consider beta blockers or rate-lowering calcium blockers such as diltiazem or verapamil

THERAPEUTIC PROCEDURES

• Carotid baroreceptor stimulation is under investigation

• Catheter-based renal artery denervation studies have had mixed results, and the role of this procedure is unclear at this time

MONITORING

• ECG and blood pressure in hospital

DIET AND ACTIVITY

• Intensify lifestyle modifications (eg, low-salt diet or DASH diet, exercise, weight loss)

ONGOING MANAGEMENT