What is the best course of action for an adult patient with a history of hypertension, currently on 20 mg of lisinopril (Angiotensin-Converting Enzyme inhibitor), who has uncontrolled hypertension with a blood pressure of 160/100 mmHg?

Management of Uncontrolled Stage 2 Hypertension on Lisinopril Monotherapy

This patient requires immediate escalation to combination therapy with two antihypertensive agents, as blood pressure of 160/100 mmHg represents stage 2 hypertension that is inadequately controlled on monotherapy and mandates prompt intensification to reduce cardiovascular morbidity and mortality. 1

Immediate Treatment Strategy

Add a second antihypertensive agent from a different class rather than simply increasing the lisinopril dose. The most effective approach is to initiate combination therapy immediately, as patients with BP ≥160/100 mmHg should be promptly treated with upward medication adjustment. 1

Preferred Combination Options

• Add a thiazide-like diuretic (chlorthalidone 12.5-25 mg or indapamide 1.25-2.5 mg) to the current lisinopril 20 mg. This combination of an ACE inhibitor plus thiazide diuretic is a first-line, evidence-based approach that has demonstrated superior cardiovascular outcomes. 1

• Alternatively, add a dihydropyridine calcium channel blocker (amlodipine 5-10 mg) to lisinopril 20 mg. This ACE inhibitor plus CCB combination is equally effective and may be preferred if the patient has contraindications to diuretics or experiences metabolic side effects. 1

• Strongly consider using a fixed-dose single-pill combination to improve adherence and simplify the regimen, which has been shown to enhance BP control rates. 1

Why Not Just Increase Lisinopril?

While the FDA label indicates lisinopril can be increased to 40 mg daily (and up to 80 mg has been studied), 2 combination therapy is superior to monotherapy dose escalation for stage 2 hypertension. 1, 3 The current guidelines explicitly recommend two-drug combinations for patients with BP >20/10 mmHg above target, which this patient clearly meets (target <130/80 mmHg). 1

Blood Pressure Target and Timeline

• Target BP is <130/80 mmHg for this patient to reduce cardiovascular risk. 1, 3

• Reassess BP within 2-4 weeks after initiating combination therapy to evaluate response and check electrolytes and renal function (particularly important when adding a diuretic or ACE inhibitor). 1

• Achieve target BP within 3 months of treatment intensification. 1, 4

If Two-Drug Combination Fails

• Escalate to triple therapy with an ACE inhibitor + CCB + thiazide/thiazide-like diuretic, preferably as a single-pill combination. 1

• If BP remains uncontrolled on maximally tolerated triple therapy, add spironolactone 25-50 mg as the fourth agent (after confirming adherence and ruling out secondary hypertension). 1

Critical Assessment Before Escalation

• Confirm medication adherence - non-adherence is a leading cause of apparent treatment resistance. 4, 5

• Rule out white-coat hypertension by obtaining home BP readings or 24-hour ambulatory BP monitoring, as office readings may overestimate true BP. 1

• Assess for secondary hypertension if BP proves difficult to control, particularly looking for renal artery stenosis, primary aldosteronism, obstructive sleep apnea, or pheochromocytoma. 3, 4

• Check renal function and electrolytes before adding a second agent, especially if adding a diuretic or continuing ACE inhibitor therapy. 1

Concurrent Lifestyle Modifications

• Implement DASH or Mediterranean diet with sodium restriction to <2,300 mg/day. 1, 3

• Recommend 150 minutes/week of moderate-intensity aerobic exercise plus resistance training 2-3 times weekly. 1, 3

• Target weight reduction if BMI >25 kg/m², aiming for BMI 20-25 kg/m² and waist circumference <94 cm (men) or <80 cm (women). 1

• Limit alcohol consumption to ≤2 drinks/day for men, ≤1 drink/day for women. 1

Common Pitfalls to Avoid

• Avoid therapeutic inertia - failing to intensify therapy promptly when BP remains uncontrolled is a major cause of poor outcomes. 4, 5

• Do not combine two RAS blockers (ACE inhibitor + ARB) as this increases adverse effects without additional benefit. 1

• Monitor for orthostatic hypotension, particularly in older patients or those with postural symptoms, when intensifying therapy. 1

• Do not use beta-blockers as routine add-on therapy unless there are compelling indications (post-MI, heart failure, angina, or rate control). 1