Antihypertensive Medications with Least Effect on Orthostatic Hypotension
Long-acting dihydropyridine calcium channel blockers (CCBs) and renin-angiotensin system (RAS) inhibitors are the preferred antihypertensive medications for patients at risk of orthostatic hypotension, as they have the least effect on postural blood pressure changes. 1
Preferred Medications for Patients with Orthostatic Hypotension
- Long-acting dihydropyridine calcium channel blockers (CCBs) should be considered first-line therapy for patients with hypertension and orthostatic hypotension, especially in elderly or frail patients 1
- RAS inhibitors (ACE inhibitors or ARBs) are also recommended as first-line agents with minimal impact on orthostatic blood pressure 1
- SGLT2 inhibitors have modest blood pressure-lowering properties and can be considered in patients with chronic kidney disease and eGFR >20 mL/min/1.73 m² 1
- Mineralocorticoid receptor antagonists (MRAs) have minimal impact on orthostatic blood pressure and can be maintained in treatment regimens when orthostatic hypotension is a concern 1
Medications to Avoid or Use with Caution
- Alpha-1 blockers (doxazosin, prazosin, terazosin) are strongly associated with orthostatic hypotension and should be avoided when possible 2
- Beta-blockers should be avoided in patients with orthostatic hypotension unless there are compelling indications 1
- Centrally-acting antihypertensives (clonidine, methyldopa, guanfacine) can worsen orthostatic hypotension and should be avoided 2
- Diuretics, particularly when causing volume depletion, can lead to orthostatic hypotension and should be used cautiously 2
Evidence Supporting Medication Choices
- In a double-blinded, cross-over study comparing enalapril (ACE inhibitor) with long-acting nifedipine (CCB) in older hypertensive patients, both medications were equally effective at reducing supine blood pressure, but enalapril significantly reduced the number of orthostatic episodes while nifedipine aggravated this phenomenon 3
- The 2024 ESC guidelines recommend that when initiating blood pressure-lowering treatment for patients aged ≥85 years and/or with moderate-to-severe frailty, long-acting dihydropyridine CCBs or RAS inhibitors should be considered first, followed by low-dose diuretics if tolerated 1
- Verapamil (a non-dihydropyridine CCB) has been shown to decrease blood pressure without worsening orthostatic hypotension and may even improve baroreflex sensitivity in patients with both hypertension and orthostatic hypotension 4
Management Approach for Patients with Both Hypertension and Orthostatic Hypotension
- Before starting or intensifying antihypertensive medication, test for orthostatic hypotension by measuring blood pressure after 5 minutes of sitting/lying and then 1 and/or 3 minutes after standing 1
- For patients with both hypertension and orthostatic hypotension, pursue non-pharmacological approaches as first-line treatment 1, 2
- When pharmacological treatment is necessary, switch medications that worsen orthostatic hypotension to alternatives rather than simply reducing the dose 1
- Consider spacing out medications to reduce synergistic hypotensive effects and implement non-pharmacological interventions such as exercise, physical training, and compression stockings 1
Special Considerations
- In patients with heart failure and low blood pressure, SGLT2 inhibitors and MRAs have the least impact on blood pressure and should be prioritized 1
- For elderly patients with orthostatic hypotension requiring antihypertensive therapy, long-acting formulations are preferred to minimize blood pressure fluctuations 3
- Patients with diabetes and orthostatic hypotension may benefit from pyridostigmine, which does not cause fluid retention or supine hypertension 1
- When treating isolated supine hypertension in patients with orthostatic hypotension, consider short-acting antihypertensives at bedtime 5
By selecting antihypertensive medications with minimal impact on orthostatic blood pressure and implementing appropriate monitoring and management strategies, it is possible to effectively treat hypertension while minimizing the risk of orthostatic hypotension and its associated complications.