My blood pressure is about 130/80 mm Hg while taking lisinopril 10 mg daily and amlodipine 10 mg daily; what further steps can I take to improve control?

Management of Uncontrolled Hypertension on Dual Therapy

Add a thiazide or thiazide-like diuretic (chlorthalidone 12.5–25 mg daily or hydrochlorothiazide 25 mg daily) as your third agent to achieve guideline-recommended triple therapy. 1

Current Blood Pressure Assessment

Your patient's blood pressure of 130s/80s mmHg represents inadequate control despite maximum-dose amlodipine (10 mg) and standard-dose lisinopril (10 mg). 1 While the systolic pressure approaches the minimum acceptable target of <140 mmHg, the optimal goal is <130/80 mmHg for most adults, particularly those with cardiovascular risk factors. 2, 1

Recommended Treatment Algorithm

Step 1: Optimize Current Medications Before Adding a Third Agent

• Increase lisinopril from 10 mg to 20 mg daily as the first step. 3 The FDA label indicates that the usual dosage range is 20–40 mg per day, and doses up to 80 mg have been used, though they do not appear to give greater effect for hypertension. 3, 4

• Lisinopril 10 mg and 20 mg produce similar peak antihypertensive effects, but the 24-hour trough effect appears dose-related across the 2.5–80 mg range. 4

• Reassess blood pressure 2–4 weeks after increasing lisinopril, with the goal of achieving target BP within 3 months of therapy modification. 1

Step 2: Add a Thiazide Diuretic if BP Remains ≥130/80 mmHg

• Add chlorthalidone 12.5–25 mg once daily (preferred) or hydrochlorothiazide 25 mg once daily to complete the evidence-based triple therapy combination of ACE inhibitor + calcium channel blocker + thiazide diuretic. 1, 5

• Chlorthalidone is preferred over hydrochlorothiazide because of its longer duration of action (24–72 hours vs 6–12 hours) and superior cardiovascular outcome data from the ALLHAT trial. 1

• This triple combination provides complementary mechanisms: volume reduction (diuretic), vasodilation (calcium channel blocker), and renin-angiotensin system blockade (ACE inhibitor). 1

Step 3: Monitor After Adding the Diuretic

• Check serum potassium and creatinine 2–4 weeks after initiating diuretic therapy to detect hypokalemia or changes in renal function. 1, 5

• Reassess blood pressure within 2–4 weeks, aiming to reach <130/80 mmHg within 3 months. 1

Important Clinical Considerations Before Intensifying Therapy

Confirm Medication Adherence First

• Non-adherence is the most common cause of apparent treatment resistance. 1 Verify adherence through direct questioning, pill counts, or pharmacy refill records before adding medications. 1

Verify True Hypertension with Home Monitoring

• Confirm elevated readings with home blood pressure monitoring (target ≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) to rule out white-coat effect. 1

Rule Out Secondary Hypertension

• If blood pressure remains severely elevated (≥160/100 mmHg) despite triple therapy, screen for secondary causes: primary aldosteronism, renal artery stenosis, obstructive sleep apnea, or pheochromocytoma. 1

Review for Interfering Substances

• NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, and herbal supplements (ephedra, St. John's wort) can all elevate blood pressure and should be identified and discontinued if possible. 1

If Blood Pressure Remains Uncontrolled on Triple Therapy

• Add spironolactone 25–50 mg daily as the preferred fourth-line agent for resistant hypertension, provided serum potassium is <4.5 mmol/L and eGFR is >45 mL/min/1.73m². 1

• Spironolactone provides additional blood pressure reductions of 20–25/10–12 mmHg when added to triple therapy. 1

• Monitor serum potassium closely when adding spironolactone to an ACE inhibitor, as hyperkalemia risk is significant. 1

• Alternative fourth-line agents if spironolactone is contraindicated include amiloride, doxazosin, eplerenone, clonidine, or a beta-blocker. 1

Lifestyle Modifications (Adjunct to Pharmacotherapy)

• Sodium restriction to <2 g/day yields a 5–10 mmHg systolic reduction and enhances the efficacy of ACE inhibitors and diuretics. 1

• Weight loss (if BMI >25 kg/m²)—losing approximately 10 kg reduces blood pressure by about 6.0/4.6 mmHg. 1

• DASH dietary pattern (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat) lowers blood pressure by roughly 11.4/5.5 mmHg. 1

• Regular aerobic exercise (≥30 minutes most days, approximately 150 minutes/week moderate intensity) reduces blood pressure by approximately 4/3 mmHg. 1

• Limit alcohol intake to ≤2 drinks/day for men and ≤1 drink/day for women. 1

Critical Pitfalls to Avoid

• Do not add a beta-blocker as the third agent unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, or atrial fibrillation requiring rate control), as beta-blockers are less effective than diuretics for stroke prevention and cardiovascular events. 1

• Do not combine lisinopril with an ARB (dual renin-angiotensin system blockade), as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1

• Do not delay treatment intensification—this patient needs action within 2–4 weeks to reduce cardiovascular risk. 1

• Do not assume treatment failure without first confirming adherence and ruling out secondary causes or interfering substances. 1

Special Considerations for This Patient

• The combination of amlodipine + lisinopril has demonstrated superior blood pressure control compared to either agent alone in patients with diabetes, chronic kidney disease, or heart failure. 5, 6

• Amlodipine 10 mg is already at the maximum recommended dose, so further dose escalation is not an option. 7

• Lisinopril can be increased to 20–40 mg daily, as doses up to 80 mg have been used, though they do not appear to give greater effect for hypertension. 3

• Peripheral edema is more common with amlodipine but may be attenuated by the addition of an ACE inhibitor. 5