Is it better to start with reducing amlodipine or candesartan in a patient with orthostatic hypotension?

Management of Orthostatic Hypotension: Reducing Candesartan vs. Amlodipine

When managing orthostatic hypotension, it is recommended to first reduce or discontinue candesartan rather than amlodipine, as RAS blockers like candesartan can worsen orthostatic hypotension and are not recommended to be used as first-line agents in patients with this condition. 1, 2

Rationale for Medication Adjustment

• The European Society of Cardiology (ESC) recommends that for patients with orthostatic hypotension, it is essential to switch BP-lowering medications that worsen orthostatic hypotension to an alternative therapy rather than simply reducing the dose 1
• Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension, with vasodilators (including RAS blockers like candesartan) being among the most important culprits 2
• Long-acting dihydropyridine calcium channel blockers (like amlodipine) are preferred first-line agents for patients with both hypertension and orthostatic hypotension 2

Medication-Specific Considerations

Candesartan (ARB)

• RAS blockers are not recommended for patients with orthostatic hypotension due to their vasodilatory effects that can exacerbate postural blood pressure drops 1, 2
• Discontinuation or modification of culprit medications like candesartan is the first-line approach to managing orthostatic hypotension 2
• ARBs can cause more significant orthostatic effects compared to dihydropyridine calcium channel blockers 2, 3

Amlodipine (Dihydropyridine CCB)

• Long-acting dihydropyridine calcium channel blockers like amlodipine are preferred for patients with hypertension and orthostatic hypotension 2
• Amlodipine has a more favorable profile for patients with orthostatic hypotension due to its gradual onset and long duration of action, which minimizes rapid blood pressure fluctuations 2, 4
• The American Heart Association recommends considering long-acting dihydropyridine calcium channel blockers as first-line therapy for patients with both hypertension and orthostatic hypotension 2

Alternative Management Strategies

• Non-pharmacological approaches should be implemented as first-line treatment for orthostatic hypotension 1, 2:

  • Increasing fluid (2-3 liters daily) and salt intake (6-9g daily) if not contraindicated 2
  • Physical counter-maneuvers (leg crossing, muscle tensing, squatting) 2
  • Compression garments for the legs and abdomen 2
  • Gradual positional changes 2
  • Smaller, more frequent meals to reduce post-prandial hypotension 1, 2

• If pharmacological treatment is needed after addressing medication causes:

  • Midodrine (alpha-1 agonist) is FDA-approved for orthostatic hypotension with an initial dose of 2.5-5mg three times daily 2, 5
  • Fludrocortisone (mineralocorticoid) at 0.05-0.1mg daily can be effective through sodium retention and vessel wall effects 2
  • Droxidopa is also FDA-approved for neurogenic orthostatic hypotension 1, 2

Monitoring and Follow-up

• The therapeutic goal should be to minimize postural symptoms rather than to restore normotension 1, 2
• Regular monitoring for adverse effects is essential, especially when adjusting antihypertensive medications 2
• Testing for orthostatic hypotension should be performed by measuring BP after 5 minutes of sitting/lying and then 1 and/or 3 minutes after standing 1, 2

Cautions and Pitfalls

• Avoid taking antihypertensive medications before situations where orthostatic symptoms are likely to occur 2
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension 2
• Elderly patients are particularly susceptible to drug-induced orthostatic hypotension due to altered pharmacokinetics and autonomic dysfunction 6, 3
• Sudden discontinuation of antihypertensive medications can cause rebound hypertension; therefore, gradual tapering is recommended 2