How to manage orthostatic hypotension in a patient taking losartan (angiotensin II receptor antagonist) for hypertension?

Managing Orthostatic Hypotension in a Patient Taking Losartan

Losartan can be safely continued in patients with orthostatic hypotension, as RAS inhibitors (including ARBs like losartan) are among the preferred antihypertensive agents that have minimal impact on orthostatic blood pressure. 1, 2

Initial Assessment and Diagnosis

• Confirm orthostatic hypotension by measuring blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing—a drop of ≥20 mmHg systolic or ≥10 mmHg diastolic confirms the diagnosis. 1

• Evaluate for reversible causes including volume depletion (from excessive diuretic use), other culprit medications (alpha-1 blockers, centrally acting agents, vasodilators), and neurogenic causes. 1

Medication Review: What to Stop vs. What to Continue

Discontinue or switch these medications that worsen orthostatic hypotension: 1, 2

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin)—these are strongly associated with orthostatic hypotension, especially in older adults 3, 2

• Diuretics if causing volume depletion—these are "the most important agents" causing drug-induced orthostatic hypotension 1, 2

• Centrally acting agents (clonidine, methyldopa) 2

• Vasodilators (hydralazine, minoxidil) 2

Continue losartan—it is a preferred agent: 1, 2

• The 2020 International Society of Hypertension guidelines explicitly recommend RAS inhibitors (including ARBs like losartan) as first-line therapy for patients with both hypertension and orthostatic hypotension. 3

• Long-acting dihydropyridine calcium channel blockers and RAS inhibitors have minimal impact on orthostatic blood pressure and are preferred in elderly/frail patients. 2

• The European Society of Cardiology recommends switching medications that worsen orthostatic hypotension to alternatives (like losartan) rather than simply reducing doses. 1

Non-Pharmacological Management (First-Line)

Implement these measures before considering pressor agents: 1

• Increase fluid intake to 2-3 liters daily and salt consumption to 6-9 grams daily (unless contraindicated by heart failure). 1

• Teach physical counter-maneuvers: leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms. 1

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling. 1

• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria and maintain favorable fluid distribution. 1

• Recommend smaller, more frequent meals to reduce postprandial hypotension. 1

• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance. 1

Pharmacological Treatment for Persistent Symptoms

If non-pharmacological measures fail, add pressor agents while continuing losartan: 1

First-Line Pressor Agent

• Midodrine 2.5-5 mg three times daily has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy. 1

• The last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 1

• Midodrine can increase standing systolic BP by 15-30 mmHg for 2-3 hours. 1

Alternative or Adjunctive Agent

• Fludrocortisone 0.05-0.1 mg daily, titrated to 0.1-0.3 mg daily, acts through sodium retention and vessel wall effects. 1

• Avoid fludrocortisone in patients with heart failure, significant cardiac dysfunction, or pre-existing supine hypertension. 1

• Monitor for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema. 1

For Refractory Cases

• Pyridostigmine 60 mg three times daily is beneficial for refractory orthostatic hypotension, particularly when supine hypertension is a concern, as it does not worsen supine blood pressure. 1

• Pyridostigmine has a favorable side effect profile compared to alternatives like fludrocortisone. 1

Treatment Goals and Monitoring

• The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1

• Measure both supine and standing blood pressure at each visit to monitor for treatment-induced supine hypertension. 1

• Reassess the patient within 1-2 weeks after medication changes. 1

• Monitor for falls and injury risk, which must be balanced against cardiovascular protection from blood pressure control. 1

Critical Pitfalls to Avoid

• Do not discontinue losartan—it is among the preferred agents for patients with both hypertension and orthostatic hypotension. 1, 2

• Do not simply reduce the dose of offending medications; switch to alternatives like losartan or calcium channel blockers instead. 1

• Do not administer midodrine after 6 PM, as this causes supine hypertension during sleep. 1

• Do not use fludrocortisone in patients with heart failure or supine hypertension. 1

• Do not overlook volume depletion as a contributing factor—correct this before adding pressor agents. 1