What's the next step for a patient with uncontrolled hypertension, currently on 5 mg of lisinopril (angiotensin-converting enzyme inhibitor), presenting with a blood pressure reading of 170 mmHg?

Uncontrolled Hypertension on Low-Dose Lisinopril

You should immediately uptitrate the lisinopril to at least 10 mg daily and add a second antihypertensive agent from a different class—specifically a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic—preferably as a fixed-dose single-pill combination. 1

Immediate Management Strategy

Confirm the Blood Pressure Reading

• Obtain at least two additional office measurements during the same visit or within 2-3 office visits to confirm persistent elevation 1
• If possible, confirm with out-of-office monitoring (home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg) to exclude white coat hypertension 1
• A single reading of 170 mmHg systolic represents Grade 2 hypertension (≥160/100 mmHg), which requires immediate pharmacological intensification 1

Assess Current Treatment Adequacy

The patient is significantly undertreated. The current 5 mg lisinopril dose is below the recommended initial dose of 10 mg for hypertension 2. The FDA label specifies that the usual dosage range is 20-40 mg daily, with doses up to 80 mg studied 2. This represents a critical treatment gap.

Rule Out Contributing Factors

Before intensifying therapy, quickly assess for:

• Medication adherence: Non-adherence is the most common cause of apparent treatment resistance 1, 3
• Interfering substances: NSAIDs are the primary culprit and should be discontinued or minimized 1
• Excessive sodium intake: Recommend <1,500 mg/day 1
• Heavy alcohol consumption: Limit to ≤2 drinks/day for men, ≤1 for women 1
• Obesity: Weight reduction improves BP control 3

Pharmacological Intensification Algorithm

Step 1: Combination Therapy (Preferred Approach)

Initiate two-drug combination therapy immediately rather than sequential monotherapy titration, as combination treatment is recommended for most patients with confirmed hypertension (BP ≥140/90 mmHg) 1:

Preferred combinations:

• ACE inhibitor (lisinopril 10-20 mg) + dihydropyridine calcium channel blocker (amlodipine 5 mg) 1
• ACE inhibitor (lisinopril 10-20 mg) + thiazide-like diuretic (chlorthalidone 12.5 mg or indapamide 1.5 mg) 1

Use fixed-dose single-pill combinations when available to improve adherence 1. The 2024 ESC Guidelines provide a Class I recommendation for this approach based on superior BP control and cardiovascular outcomes data 1.

Step 2: If BP Remains Uncontrolled After 1-3 Months

• Increase to full-dose two-drug combination (e.g., lisinopril 40 mg + amlodipine 10 mg) 1
• Reassess at 1 month if possible, as faster titration reduces cardiovascular risk 1

Step 3: Triple Combination Therapy

If BP remains uncontrolled on maximally tolerated two-drug combination:

• Add the third major drug class: RAS blocker + dihydropyridine CCB + thiazide/thiazide-like diuretic 1
• Preferably use a single-pill triple combination 1

Step 4: Resistant Hypertension Management

If BP remains uncontrolled on maximally tolerated triple therapy:

• Add spironolactone 12.5-50 mg daily as the fourth-line agent 1
• Spironolactone provides significant additional BP reduction (average 25/12 mmHg) in resistant hypertension 1
• Refer to hypertension specialist for evaluation of secondary causes 1

Target Blood Pressure Goals

Target systolic BP of 120-129 mmHg to reduce cardiovascular risk, provided treatment is well tolerated 1. If this target cannot be achieved due to poor tolerance, apply the "as low as reasonably achievable" (ALARA) principle 1.

Critical Pitfalls to Avoid

Do Not Delay Treatment Intensification

• Therapeutic inertia is a major contributor to poor BP control 3, 4
• Grade 2 hypertension (≥160/100 mmHg) requires immediate drug treatment, not a prolonged trial of lifestyle modification alone 1

Do Not Use Suboptimal Diuretic Therapy

• If using hydrochlorothiazide, doses ≥25 mg are needed for adequate effect 1
• Thiazide-like diuretics (chlorthalidone, indapamide) are preferred over hydrochlorothiazide for superior BP lowering and cardiovascular outcomes 1
• In patients with chronic kidney disease (eGFR <30 mL/min), switch to loop diuretics 1

Do Not Combine Two RAS Blockers

• Never combine an ACE inhibitor with an ARB—this increases adverse events without additional benefit 1

Monitoring Plan

• Reassess BP within 1-3 months after treatment intensification (1 month preferred) 1
• Achieve target BP within 3 months of initiating or intensifying therapy 1
• Monitor serum potassium and creatinine within 1-2 weeks after adding or uptitrating ACE inhibitor, especially if adding spironolactone 1
• Continue BP-lowering treatment lifelong, even beyond age 85 if well tolerated 1

Special Considerations

Age and Frailty

• In patients aged ≥85 years or with moderate-to-severe frailty, consider monotherapy initially rather than combination therapy 1
• Individualize targets based on frailty status, but do not withhold effective treatment 1

Secondary Hypertension Screening

If BP remains uncontrolled despite adherence to optimal three-drug therapy including a diuretic, evaluate for:

• Primary aldosteronism (most common secondary cause in resistant hypertension) 1
• Obstructive sleep apnea (neck circumference >40 cm, snoring, daytime sleepiness) 1
• Renal artery stenosis (flash pulmonary edema, abdominal bruit) 1
• Chronic kidney disease (check eGFR and urinalysis) 1