How should antihypertensive therapy be adjusted in an 87‑year‑old woman with type 2 diabetes, hypertension, hypothyroidism (on levothyroxine), hyperlipidaemia (on atorvastatin) and metformin who has morning orthostatic hypotension and later‑day systolic hypertension (~160 mm Hg)?

Managing Later-Day Systolic Hypertension in an Elderly Patient with Morning Orthostatic Hypotension

Adjust the timing of her current antihypertensive medication to later in the day (avoiding morning doses), and if she is not already on one, initiate or switch to a long-acting dihydropyridine calcium channel blocker (such as amlodipine) or RAS inhibitor (ACE inhibitor or ARB) taken in the afternoon or early evening to target the later-day blood pressure elevation while minimizing morning orthostatic effects. 1, 2

Rationale for Medication Selection and Timing

First-Line Agent Choice

• Long-acting dihydropyridine calcium channel blockers (such as amlodipine) or RAS inhibitors are specifically recommended by the European Society of Cardiology as first-line therapy for patients with both hypertension and orthostatic hypotension because they have minimal effects on orthostatic blood pressure. 1, 2
• These agents are superior to diuretics, beta-blockers, and alpha-blockers in this clinical scenario, as the latter medications can significantly worsen orthostatic hypotension. 2

Timing Strategy

• Administer the antihypertensive medication in the afternoon or early evening (around 2-4 PM) to achieve peak effect during the later-day period when her systolic pressure reaches 160 mmHg, while avoiding morning administration that would worsen her orthostatic hypotension. 1, 2
• This chronotherapeutic approach addresses the diurnal variation in her blood pressure without compromising morning postural stability. 1

Treatment Targets and Thresholds

Blood Pressure Goals

• At age 87, her systolic blood pressure of 160 mmHg clearly exceeds treatment thresholds, as guidelines recommend initiating therapy at ≥150 mmHg for patients over 80 years. 3
• Target blood pressure should be <150/90 mmHg based on high-quality evidence from the HYVET trial in patients ≥80 years. 3
• The goal is to reduce her later-day systolic pressure below 160 mmHg while maintaining adequate morning blood pressure to prevent symptomatic orthostatic hypotension. 1, 2

Diabetes Consideration

• Given her type 2 diabetes (a compelling indication), RAS inhibitors (ACE inhibitors or ARBs) may offer additional renal and cardiovascular protection beyond blood pressure control. 4

Concurrent Non-Pharmacological Management for Orthostatic Hypotension

Fluid and Salt Management

• Increase fluid intake to 2-3 liters daily and salt consumption to 6-9 grams daily (unless contraindicated by heart failure) to help manage her morning orthostatic hypotension. 1, 2
• This expansion of intravascular volume will improve morning postural tolerance while not interfering with later-day blood pressure control. 1

Positional Strategies

• Elevate the head of her bed by 10 degrees during sleep to prevent nocturnal polyuria and ameliorate nocturnal hypertension, which may contribute to morning orthostatic hypotension. 1
• Teach gradual staged movements with postural changes in the morning—sitting at bedside for 1-2 minutes before standing. 2
• Physical counter-maneuvers such as leg crossing, squatting, and muscle tensing can help alleviate symptomatic orthostatic episodes. 1

Compression Garments

• Consider waist-high compression stockings or abdominal binders to reduce venous pooling during morning hours. 1

Medication Review and Adjustment

Discontinue or Modify Problematic Medications

• Immediately review and discontinue or switch medications that worsen orthostatic hypotension, including diuretics (if she is taking them), alpha-1 adrenergic blockers, and nitrates. 2
• If she is currently on a diuretic for blood pressure control, this should be discontinued or reduced, as diuretics are particularly problematic for orthostatic hypotension and thiazide-like diuretics can be added later only if needed for additional blood pressure control. 4, 2

Dosing Strategy

Initial Dosing

• Start with the lowest recommended dose and titrate slowly, especially given her age and orthostatic hypotension. 2
• For amlodipine, start at 2.5-5 mg once daily in the afternoon. 1
• For an ACE inhibitor like lisinopril, start at 5-10 mg once daily in the afternoon; for captopril, start at 12.5-25 mg twice daily (avoiding morning dose). 5

Titration Schedule

• Reassess within 1-2 weeks after initiating treatment to check for orthostatic symptoms and blood pressure response. 1
• If blood pressure remains uncontrolled, increase the dose gradually at 2-4 week intervals. 1, 3

Critical Monitoring Requirements

Orthostatic Vital Signs

• Measure blood pressure in both supine/sitting and standing positions at every visit, checking after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing. 1, 2
• Orthostatic hypotension is defined as a drop of ≥20 mmHg systolic or ≥10 mmHg diastolic. 2, 6

Timing of Blood Pressure Measurements

• Obtain blood pressure readings at different times of day—specifically in the morning (when orthostatic hypotension is problematic) and in the afternoon/evening (when hypertension peaks at 160 mmHg). 1
• Consider home blood pressure monitoring to document the diurnal pattern and treatment response. 1

Laboratory Monitoring

• Monitor electrolytes, BUN, and creatinine within 2-4 weeks if using an ACE inhibitor or ARB, particularly given her diabetes and metformin use. 3
• Check for hyperkalemia, especially with RAS inhibitors in diabetic patients. 1

Symptom Assessment

• Assess for symptoms of orthostatic hypotension including dizziness, lightheadedness, falls, syncope, visual disturbances, and cognitive slowing. 6, 7
• Monitor for symptoms of inadequate blood pressure control including headache, chest pain, or dyspnea. 1

If Pharmacological Treatment for Orthostatic Hypotension Becomes Necessary

Indications

• If non-pharmacological measures and medication timing adjustments fail to adequately control her morning orthostatic symptoms, consider adding a pressor agent. 2

First-Line Pressor Agent

• Midodrine is the first-line agent for persistent symptomatic orthostatic hypotension, starting at 2.5-5 mg three times daily (morning, midday, and mid-afternoon). 1, 2, 6
• Critical: The last dose must be at least 3-4 hours before bedtime to prevent supine hypertension, which could worsen her later-day blood pressure elevation. 2

Alternative Agent

• Fludrocortisone 0.05-0.1 mg once daily in the morning can be considered as an alternative, but it is contraindicated if she develops supine hypertension. 1, 2

Common Pitfalls to Avoid

Overaggressive Morning Blood Pressure Lowering

• Do not administer antihypertensive medications in the morning, as this will worsen her orthostatic hypotension and increase fall risk. 1, 2
• Avoid the temptation to treat her morning blood pressure readings if they are lower due to orthostatic changes. 2

Inappropriate Diuretic Use

• Diuretics are particularly problematic in patients with orthostatic hypotension and should be avoided or minimized. 2
• While thiazide-like diuretics (chlorthalidone) are generally preferred first-line agents in elderly hypertensive patients, they are specifically contraindicated in this patient with orthostatic hypotension. 3, 2

Ignoring Supine Hypertension

• Monitor for the development of supine hypertension (blood pressure elevation when lying down), which commonly coexists with orthostatic hypotension and can complicate management. 2, 7
• If supine hypertension develops, head-of-bed elevation becomes even more critical. 1

Inadequate Follow-Up

• Schedule follow-up within 2-4 weeks after medication initiation to assess response and adjust therapy. 3
• Aim to achieve target blood pressure within 3 months. 1, 2

Evidence Quality Considerations

• The recommendation for calcium channel blockers or RAS inhibitors in patients with orthostatic hypotension comes from European Society of Cardiology and American College of Cardiology guidelines, representing high-quality evidence. 1, 2
• The blood pressure target of <150/90 mmHg for patients ≥80 years is based on the HYVET trial, which was stopped early for benefit and demonstrated mortality reduction. 3
• The chronotherapeutic approach (timing medications to match blood pressure patterns) is supported by physiologic principles and clinical experience, though large randomized trials specifically testing this strategy in patients with diurnal blood pressure variation are limited. 1, 2