How to start guideline-directed medical therapy in a patient with orthostatic hypotension?

Managing Guideline-Directed Medical Therapy in Patients with Orthostatic Hypotension

When initiating guideline-directed medical therapy (GDMT) in patients with orthostatic hypotension, first stabilize the orthostatic hypotension with non-pharmacological measures and specific OH medications before starting cardiac medications at low doses with careful titration.

Assessment of Orthostatic Hypotension

• Orthostatic hypotension is defined as a decrease in systolic blood pressure of ≥20 mmHg or a decrease in diastolic blood pressure of ≥10 mmHg within 3 minutes of standing compared to sitting or supine position 1
• Measure blood pressure after the patient has been supine for 5 minutes, then at 1 and 3 minutes after standing 1
• Document symptoms during position changes (lightheadedness, dizziness, blurred vision, weakness)

Step 1: Non-Pharmacological Management of Orthostatic Hypotension

Start with these interventions before initiating GDMT:

1. Volume expansion:

   • Increase fluid intake (480 mL of water can acutely raise blood pressure) 2, 1
   • Increase salt intake (unless contraindicated) 2
   • Small, frequent meals with reduced carbohydrate content 2

2. Physical countermeasures:

   • Compression garments for legs and abdomen 2
   • Physical counter-pressure maneuvers (leg crossing, muscle tensing, squatting) 2, 1
   • Avoid prolonged standing 2
   • Use of portable chairs when needed 2

3. Positional adjustments:

   • Elevate head of bed 10-15 cm during sleep to prevent supine hypertension 1
   • Gradual staged movements with postural change 1

4. Medication review:

   • Identify and discontinue/reduce medications that worsen orthostatic hypotension 2
   • Common culprits: diuretics, vasodilators, antidepressants, alpha-blockers

Step 2: Pharmacological Management of Orthostatic Hypotension

If non-pharmacological measures are insufficient, add medications for orthostatic hypotension:

1. First-line medications:

   • Midodrine: Start at 2.5-5 mg three times daily (last dose at least 3-4 hours before bedtime), titrate up to 10 mg TID 2, 1, 3
     • Monitor for supine hypertension, pilomotor reactions, urinary retention
   • Fludrocortisone: Start at 0.05-0.1 mg daily, titrate to 0.1-0.3 mg daily 2, 1
     • Monitor for supine hypertension, hypokalemia, edema, heart failure

2. Second-line medications (if first-line inadequate):

   • Droxidopa: For neurogenic orthostatic hypotension 2, 1
   • Pyridostigmine: For refractory cases 2, 1

Step 3: Initiating GDMT in Patients with Orthostatic Hypotension

Once orthostatic hypotension is stabilized:

1. Beta-blockers:

   • Start with shorter-acting agents (metoprolol tartrate, atenolol) at lowest doses 2, 1
   • Administer at bedtime if possible to minimize daytime orthostatic effects
   • Monitor closely for worsening orthostatic symptoms
   • Titrate very gradually (e.g., 12.5 mg metoprolol tartrate daily, increasing by 12.5 mg weekly)

2. ACE inhibitors/ARBs:

   • Start at 25-50% of usual starting dose (e.g., enalapril 1.25 mg daily) 2
   • Administer at bedtime to minimize daytime orthostatic effects
   • Titrate slowly every 1-2 weeks with orthostatic BP monitoring
   • Consider shorter-acting agents initially

3. Mineralocorticoid receptor antagonists (MRAs):

   • Start at very low doses (e.g., spironolactone 12.5 mg daily)
   • May be better tolerated than other diuretics in OH patients
   • Monitor potassium and renal function closely

4. Diuretics:

   • Use with extreme caution as they can worsen orthostatic hypotension
   • Consider only if volume overload is present
   • Use lowest effective dose, preferably at bedtime

Step 4: Monitoring and Titration

• Measure orthostatic vital signs before each dose increase
• Instruct patients to keep a symptom diary
• Titrate medications more slowly than in patients without orthostatic hypotension
• Consider home BP monitoring in sitting and standing positions
• Schedule more frequent follow-up visits during medication initiation/titration
• Adjust medications based on symptoms rather than targeting specific BP values 4

Special Considerations

• For elderly patients (≥85 years), consider long-acting dihydropyridine CCBs or low-dose RAS inhibitors as initial therapy 1
• In patients with supine hypertension, shorter-acting agents administered during daytime hours may be preferred 2
• For patients with heart failure and orthostatic hypotension, prioritize beta-blockers and ACE inhibitors/ARBs but start at very low doses
• Continue medications only in patients who report significant symptomatic improvement 3

Common Pitfalls to Avoid

• Initiating multiple GDMT medications simultaneously
• Starting with standard doses of GDMT medications
• Rapid titration of medications
• Focusing only on supine BP targets while ignoring orthostatic symptoms
• Neglecting non-pharmacological measures once medications are started
• Administering medications at times that worsen orthostatic symptoms (e.g., morning doses)

By following this structured approach, clinicians can successfully implement GDMT in patients with orthostatic hypotension while minimizing adverse effects and maximizing therapeutic benefits.