What is the best treatment for a patient with hypertension and orthostatic hypotension?

Treatment of Hypertension with Orthostatic Hypotension

For patients with both hypertension and orthostatic hypotension, switch to long-acting dihydropyridine calcium channel blockers (such as amlodipine) or RAS inhibitors (ACE inhibitors or ARBs) as first-line antihypertensive therapy, while simultaneously implementing non-pharmacological measures to manage the orthostatic component. 1

Initial Assessment and Medication Review

Before initiating any treatment changes, document the severity of orthostatic hypotension by measuring blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing 2, 1. A drop of ≥20 mmHg systolic or ≥10 mmHg diastolic confirms orthostatic hypotension 2.

Immediately discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses 1. Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension 1. Priority medications to discontinue include:

• Diuretics - these are among the most important culprits and should be stopped first 2, 1
• Alpha-1 adrenergic blockers (prazosin, terazosin, doxazosin) 1, 3
• Beta-blockers - these worsen orthostatic hypotension and are not effective for this condition 2, 1
• Nitrates - these may aggravate orthostatic hypotension 2

Antihypertensive Selection for Dual Management

The European Society of Cardiology specifically recommends long-acting dihydropyridine calcium channel blockers or RAS inhibitors as preferred first-line agents for patients with both hypertension and orthostatic hypotension 1, 4. This recommendation is particularly strong for elderly patients (≥85 years) 1.

Why These Agents Are Preferred:

• Calcium channel blockers (amlodipine) and RAS inhibitors have minimal effects on orthostatic blood pressure compared to diuretics and alpha-blockers 1, 4
• They provide effective blood pressure control while reducing the risk of exacerbating postural symptoms 1
• Start with lower doses and titrate slowly, especially in older patients 4

Target Blood Pressure:

• Aim for predialysis blood pressure of 140/90 mmHg (measured sitting), provided there is no substantial orthostatic hypotension and these levels don't cause symptomatic intradialytic hypotension 2
• For most patients, target 120-129 mmHg systolic if well tolerated 4
• The therapeutic goal is minimizing postural symptoms, not necessarily normalizing standing blood pressure 1, 5

Non-Pharmacological Management (Implement Simultaneously)

These measures are essential and should be started immediately alongside medication adjustments 1, 6:

Volume Expansion:

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure 1, 7
• Increase salt intake to 6-9 grams daily if not contraindicated 2, 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 1

Positional Strategies:

• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria and maintain favorable fluid distribution 1
• Teach gradual staged movements with postural changes 1
• Avoid prolonged standing and hot environments 6

Physical Counter-Maneuvers:

• Leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes, particularly effective in patients under 60 years 1
• These maneuvers can be implemented immediately when symptoms occur 1

Compression Garments:

• Waist-high compression stockings (30-40 mmHg) and abdominal binders reduce venous pooling 1
• Thigh-high compression alone is less effective than abdominal compression 1

Dietary Modifications:

• Smaller, more frequent meals to reduce postprandial hypotension 1
• Avoid alcohol as it causes both autonomic neuropathy and central volume depletion 1

Pharmacological Treatment for Persistent Orthostatic Symptoms

If non-pharmacological measures fail to adequately control orthostatic symptoms despite optimized antihypertensive therapy, consider adding specific agents for orthostatic hypotension 1:

First-Line Pharmacological Options:

Midodrine is the first-line agent with the strongest evidence base (three randomized placebo-controlled trials) 1, 3:

• Start at 2.5-5 mg three times daily 1, 3
• Can increase standing systolic BP by 15-30 mmHg for 2-3 hours 1
• Critical: Last dose must be at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension 1, 3
• Monitor for supine hypertension, which is the most important limiting factor 3

Fludrocortisone as alternative or addition to midodrine 1, 7:

• Start at 0.05-0.1 mg once daily, titrate to 0.1-0.3 mg daily 1
• Acts through sodium retention and vessel wall effects 1
• Contraindicated in active heart failure or supine hypertension 1
• Monitor for hypokalemia, peripheral edema, and supine hypertension 1, 8

Droxidopa is FDA-approved and particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 1

Combination Therapy:

If monotherapy is insufficient, combine midodrine with fludrocortisone as they work through complementary mechanisms (alpha-1 adrenergic stimulation versus sodium retention) 1. When combining, ensure adequate salt (6-10g daily) and fluid (2-3L daily) intake unless contraindicated 1.

Monitoring and Follow-Up

• Reassess within 1-2 weeks after medication changes 1
• Measure orthostatic vital signs at each follow-up visit 1
• Monitor for supine hypertension development, which can cause end-organ damage 1
• Check electrolytes, BUN, and creatinine if using fludrocortisone 1
• Aim to achieve target blood pressure within 3 months 4

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications - switch to alternative therapy instead 1
• Do not combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring 1
• Do not administer midodrine after 6 PM due to risk of nocturnal supine hypertension 1, 3
• Do not use fludrocortisone in patients with heart failure or pre-existing supine hypertension 1
• Do not overlook volume depletion as a contributing factor 1
• Do not use beta-blockers as they worsen orthostatic hypotension and are not effective 1

Special Considerations

The risk of falls and injury from postural hypotension must be balanced against cardiovascular protection from treating hypertension 1. In older patients with widely variable blood pressure, consider a slow titration approach 2. The misperception that many elderly have "brittle hypertension" has contributed to widespread inadequacy of drug titration and poor blood pressure control 2.

For patients with diabetes and orthostatic hypotension, assess for cardiovascular autonomic neuropathy 1. Orthostatic hypotension carries a 64% increase in age-adjusted mortality and increased risk of falls and fractures 2.