RAS Inhibitors for Older Patients with Refractory Orthostatic Hypotension and Hypertension
RAS inhibitors (ACE inhibitors or ARBs) are explicitly recommended as first-line antihypertensive agents for older patients with orthostatic hypotension because they have minimal impact on orthostatic blood pressure. 1
Why RAS Inhibitors Are Preferred
Long-acting dihydropyridine calcium channel blockers and RAS inhibitors should be considered first-line therapy for patients aged ≥85 years and/or with moderate-to-severe frailty who have both hypertension and orthostatic hypotension. 1
RAS inhibitors are among the antihypertensive medications with the least effect on orthostatic blood pressure, making them ideal for this population. 1
In a direct comparison study, enalapril (an ACE inhibitor) significantly reduced orthostatic episodes in older hypertensive patients, whereas nifedipine aggravated orthostatic hypotension—the orthostatic decline in systolic blood pressure after 5 minutes of standing was only 2.4 ± 1.6 mm Hg with enalapril versus 8.7 ± 4.8 mm Hg with nifedipine. 2
Specific RAS Inhibitor Options
ACE Inhibitors
- Lisinopril is well-studied in elderly populations and has been shown to effectively lower blood pressure without causing postural hypotension. 3
- In elderly patients, lisinopril 5-40 mg daily (median 20 mg) significantly reduced sitting blood pressure with no significant alteration in heart rate and no postural hypotension. 3
- Lisinopril is effective in 68.2-89.1% of elderly patients with hypertension, with dosages ranging from 2.5-40 mg/day. 4
ARBs
- Losartan and other ARBs are equally appropriate alternatives to ACE inhibitors for patients with orthostatic hypotension. 1
Critical Dosing and Initiation Strategy
- Start at low doses and titrate gradually while monitoring renal function and potassium within 1-2 weeks. 1
- For patients with glomerular filtration rate (GFR) 30-60 mL/min, start lisinopril at 5 mg daily; for GFR >60 mL/min, start at 10 mg daily. 3
- Target doses proven effective in clinical trials should be aimed for, but intermediate doses are acceptable if target doses are not tolerated. 1
Medication Review Before Starting RAS Inhibitors
Before initiating RAS inhibitors, discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses: 1
- Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are strongly associated with orthostatic hypotension and should be discontinued. 1, 5
- Centrally-acting drugs (clonidine, methyldopa, guanfacine) should be switched to alternatives. 1
- Diuretics causing volume depletion should be reduced or discontinued before starting RAS inhibitors. 1, 6
- Beta-blockers should be avoided unless there are compelling indications (e.g., heart failure, post-MI). 1, 7
Monitoring Requirements
- Measure blood pressure after 5 minutes of sitting/lying, then at 1 and/or 3 minutes after standing before starting treatment and at each follow-up visit. 1, 5
- Monitor renal function and potassium within 1-2 weeks of initiation or dose changes. 1
- Reassess the patient within 1-2 weeks after medication changes. 5
Critical Contraindications and Cautions
- Use ACE inhibitors with caution in patients with systolic blood pressure <80 mm Hg, serum creatinine >3 mg/dL, or serum potassium >5.0-5.5 mEq/L. 1
- The only absolute contraindications are life-threatening angioedema, pregnancy, or anuric renal failure from previous exposure. 1
- Do NOT combine two RAS inhibitors (ACE inhibitor + ARB) as dual blockade is associated with increased risks of hypotension, syncope, hyperkalemia, and acute renal failure. 8, 6
Important Drug Interactions
- NSAIDs (including COX-2 inhibitors) can deteriorate renal function and attenuate the antihypertensive effect of RAS inhibitors, particularly in elderly or volume-depleted patients. 8, 6
- Potassium-sparing diuretics and potassium supplements increase hyperkalemia risk—monitor serum potassium frequently. 8, 6
- Lithium toxicity can occur with RAS inhibitors—monitor serum lithium levels during concurrent use. 8, 6
- Ensure appropriate diuretic dosing to avoid both fluid overload and excessive volume depletion when initiating RAS inhibitors. 1
Non-Pharmacological Measures to Implement Concurrently
- Increase fluid intake to 2-3 liters daily and salt intake to 6-9 grams daily (unless contraindicated by heart failure). 5
- Teach physical counter-maneuvers: leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes. 5
- Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling. 5
- Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria and supine hypertension. 5
- Recommend smaller, more frequent meals to reduce post-prandial hypotension. 5
Common Pitfalls to Avoid
- Do not inappropriately withhold RAS inhibitors from patients who would benefit (heart failure, post-MI, diabetes, chronic kidney disease) simply because they have orthostatic hypotension. 1
- Do not simply reduce the dose of offending medications—switch to alternatives instead. 1, 5
- Do not combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring. 5
- Asymptomatic orthostatic hypotension during treatment should not trigger automatic down-titration of therapy, as intensive blood pressure lowering may actually reduce the risk of orthostatic hypotension by improving baroreflex function. 5