What additional medication can be added to lisinopril (Angiotensin-Converting Enzyme Inhibitor) 40 mg for an 85-year-old female with uncontrolled hypertension?

Add a Dihydropyridine Calcium Channel Blocker (DHP-CCB) or Thiazide/Thiazide-like Diuretic to Lisinopril 40 mg

For an 85-year-old female with uncontrolled hypertension on lisinopril 40 mg, add either a dihydropyridine calcium channel blocker (such as amlodipine) or a thiazide/thiazide-like diuretic (such as chlorthalidone or indapamide) as the next step, with preference for a single-pill combination to improve adherence. 1

Algorithmic Approach to Second-Line Agent Selection

Step 1: Add a DHP-CCB or Thiazide Diuretic

The 2024 ESC Guidelines and 2020 ISH Guidelines both recommend that after maximizing ACE inhibitor therapy, the next step is adding either:

• A dihydropyridine calcium channel blocker (amlodipine 5-10 mg) 1
• A thiazide-like diuretic (chlorthalidone 12.5-25 mg or indapamide 1.25-2.5 mg) 1

Both options have demonstrated effective BP reduction and cardiovascular event reduction in clinical trials. 1

Step 2: Prioritize Single-Pill Combinations

Use a fixed-dose single-pill combination of lisinopril plus amlodipine or lisinopril plus a thiazide diuretic to maximize adherence, which is particularly important in elderly patients. 1 Single-pill combinations improve medication-taking behavior and BP control compared to free-drug combinations. 1

Step 3: Consider Patient-Specific Factors

For this 85-year-old patient, assess frailty status before proceeding:

• If non-frail: Target BP of 120-129 mmHg systolic is appropriate with combination therapy 1
• If frail or very elderly (>85 years): Consider starting with lower doses and individualizing targets based on tolerability 1

The 2020 ISH Guidelines specifically note that monotherapy may be considered in patients aged >80 years or those who are frail, but this patient is already on monotherapy that has failed, so combination therapy is indicated. 1

If Two-Drug Combination Fails: Move to Three-Drug Therapy

If BP remains uncontrolled after adding a second agent, escalate to a three-drug combination: ACE inhibitor + DHP-CCB + thiazide/thiazide-like diuretic, preferably as a single-pill combination. 1

Research evidence supports that when amlodipine and lisinopril fail to control BP, adding a thiazide diuretic (bendrofluazide in the study) produces significantly greater BP reduction than adding a beta-blocker. 2

Fourth-Line Options for Resistant Hypertension

If BP remains uncontrolled on maximal three-drug therapy (lisinopril + DHP-CCB + thiazide diuretic), add spironolactone 25-50 mg daily as the fourth agent. 1, 3

Alternative fourth-line agents if spironolactone is not tolerated or contraindicated include: 1

• Amiloride
• Doxazosin
• Eplerenone
• Clonidine
• Beta-blocker (though less effective than spironolactone in this setting)

The rationale for spironolactone is that it addresses aldosterone escape that can occur with long-term ACE inhibitor therapy, providing complementary mechanism of action. 3

Critical Considerations for This 85-Year-Old Patient

Dosing Adjustments

• Start with lower doses in elderly patients due to decreased drug clearance and increased AUC (40-60% higher in elderly). 4
• For amlodipine, consider starting at 2.5 mg daily in elderly patients before titrating to 5-10 mg. 4

Monitoring Requirements

• Achieve target BP within 3 months of initiating combination therapy 1
• Monitor for orthostatic hypotension, which is more common in elderly patients 1
• Check renal function and potassium after adding diuretics or when escalating therapy 1

Common Pitfalls to Avoid

• Do NOT combine two RAS blockers (ACE inhibitor + ARB) - this is explicitly not recommended 1
• Do NOT discontinue lisinopril - continue the ACE inhibitor as part of combination therapy 1
• Do NOT use beta-blockers as second-line agents unless there are compelling indications (post-MI, heart failure with reduced ejection fraction, angina, or rate control) 1

Medication Timing

• Take medications at the most convenient time of day to establish habitual pattern and improve adherence - timing (morning vs. evening) does not significantly affect outcomes 1

Blood Pressure Targets

Target systolic BP of 120-129 mmHg if well-tolerated, even in patients >85 years old, as long as treatment is continued lifelong if tolerated. 1 However, if poorly tolerated, use the "as low as reasonably achievable" (ALARA) principle. 1

The 2020 ISH Guidelines recommend targeting BP <140/90 mmHg at minimum, with individualization for elderly based on frailty. 1