What is the most appropriate next step in antihypertensive therapy for a 78‑year‑old woman with chronic obstructive pulmonary disease and hypertension who is taking lisinopril 40 mg daily and hydrochlorothiazide 25 mg daily and has a persistently elevated systolic blood pressure of 177 mm Hg?

Management of Uncontrolled Hypertension in a 78-Year-Old with COPD

Add a calcium channel blocker (amlodipine 5–10 mg daily) as the third antihypertensive agent to achieve guideline-recommended triple therapy (ACE inhibitor + diuretic + calcium channel blocker).

Current Clinical Situation

This patient has stage 2 hypertension (systolic BP 177 mmHg) despite dual therapy with lisinopril 40 mg and hydrochlorothiazide 25 mg—both at maximum or near-maximum doses. 1

• The systolic BP of 177 mmHg is >30 mmHg above target, warranting immediate addition of a third agent rather than simple dose adjustment. 1
• The current regimen represents only two of the three major drug classes recommended for triple therapy. 1

Recommended Treatment Algorithm

Step 1: Add Calcium Channel Blocker

Add amlodipine 5 mg once daily, titrating to 10 mg if needed after 2–4 weeks. 1, 2

• The 2024 ESC guidelines explicitly state that when BP is not controlled with a two-drug combination, increasing to a three-drug combination is recommended—usually a RAS blocker with a dihydropyridine calcium channel blocker and a thiazide/thiazide-like diuretic. 1
• This creates the evidence-based triple therapy: ACE inhibitor + thiazide diuretic + calcium channel blocker, targeting three complementary mechanisms (renin-angiotensin blockade, volume reduction, and vasodilation). 1, 2

Step 2: Optimize Diuretic Component (Alternative Consideration)

If amlodipine is contraindicated or not tolerated, consider replacing hydrochlorothiazide 25 mg with chlorthalidone 12.5–25 mg daily before adding a fourth agent. 2

• Chlorthalidone provides superior 24-hour BP control and stronger cardiovascular outcome data compared with hydrochlorothiazide. 2
• The current HCTZ dose of 25 mg is appropriate, but chlorthalidone offers longer duration of action (24–72 hours vs 6–12 hours). 2

Special Considerations for COPD

Calcium channel blockers are safe and preferred in patients with COPD. 1, 3

• A 52-week study in hypertensive patients with COPD demonstrated that lisinopril (ACE inhibitor) and nifedipine (calcium channel blocker) both effectively controlled BP without adverse effects on pulmonary function. 3
• Beta-blockers should be avoided in this patient with COPD unless there are compelling indications (post-MI, heart failure, angina), as they are contraindicated in active bronchospasm. 1
• The 2004 British Hypertension Society guidelines list "asthma or chronic obstructive pulmonary disease" as a compelling contraindication to beta-blockers. 1

Blood Pressure Targets and Monitoring

Target BP: <140/90 mmHg minimum, ideally 120–129 mmHg systolic if well tolerated. 1

• For a 78-year-old, individualize based on frailty, but do not withhold appropriate treatment solely based on age. 2
• Reassess BP within 2–4 weeks after adding amlodipine, with the goal of achieving target within 3 months. 1, 2

If Blood Pressure Remains Uncontrolled on Triple Therapy

Fourth-Line Agent: Spironolactone

Add spironolactone 25–50 mg daily if BP remains ≥140/90 mmHg after optimizing triple therapy. 1, 2

• The 2024 ESC guidelines specifically recommend spironolactone for resistant hypertension, providing additional BP reductions of 20–25/10–12 mmHg. 1, 2
• Monitor serum potassium and creatinine 2–4 weeks after initiation due to hyperkalemia risk when combined with lisinopril. 2

Alternative Fourth-Line Agents

If spironolactone is contraindicated or not tolerated, consider: 1

• Eplerenone 50–200 mg daily (may need twice-daily dosing)
• Beta-blockers (vasodilating types: carvedilol, nebivolol, labetalol)—only if COPD is stable and no active bronchospasm
• Doxazosin, amiloride, or centrally acting agents as last resort

Critical Steps Before Adding Medication

Verify Adherence

Non-adherence is the most common cause of apparent treatment resistance. 2

• Use pill counts, pharmacy refill data, or direct questioning to confirm the patient is taking medications as prescribed. 2

Confirm True Hypertension

Arrange home BP monitoring or 24-hour ambulatory monitoring to exclude white-coat hypertension. 2, 4

• Home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg confirms true hypertension. 2

Screen for Interfering Substances

Review for medications or substances that elevate BP: 2

• NSAIDs (most common)
• Decongestants (pseudoephedrine, phenylephrine)
• Systemic corticosteroids
• Herbal supplements (ephedra, licorice, St. John's wort)

Rule Out Secondary Hypertension

For BP ≥160/100 mmHg resistant to dual therapy, screen for: 2

• Primary aldosteronism (most common secondary cause)
• Renal artery stenosis
• Obstructive sleep apnea
• Pheochromocytoma

Lifestyle Modifications (Adjunct to Pharmacotherapy)

Comprehensive lifestyle changes can lower systolic/diastolic BP by 10–20 mmHg. 2

• Sodium restriction to <2 g/day yields 5–10 mmHg systolic reduction. 1, 2
• DASH dietary pattern reduces BP by approximately 11.4/5.5 mmHg. 2
• Weight loss (if BMI ≥25 kg/m²)—losing 10 kg reduces BP by about 6.0/4.6 mmHg. 2
• Regular aerobic exercise (≥30 minutes most days) lowers BP by approximately 4/3 mmHg. 2
• Limit alcohol to ≤1 drink/day for women, ≤2 drinks/day for men. 2

Common Pitfalls to Avoid

• Do not add a beta-blocker as the third agent in a patient with COPD unless there are compelling indications (post-MI, heart failure, angina). 1
• Do not combine lisinopril with an ARB (dual RAS blockade)—this increases hyperkalemia and acute kidney injury risk without cardiovascular benefit. 1, 2
• Do not delay treatment intensification—stage 2 hypertension (177/74 mmHg) requires prompt action within 2–4 weeks to reduce cardiovascular risk. 1, 2
• Do not uptitrate lisinopril beyond 40 mg as the primary strategy—combination therapy is more effective than monotherapy dose escalation. 1, 5
• Do not assume treatment failure without first confirming adherence and excluding secondary causes. 2

Single-Pill Combination Preference

Strongly prefer single-pill combinations (e.g., lisinopril/HCTZ/amlodipine fixed-dose combination) when available, as they significantly improve adherence and persistence. 1