In a patient with a recent ischemic stroke who remains hypertensive on lisinopril 40 mg daily, what additional antihypertensive medication should be added?

Additional Antihypertensive for Post-Stroke Blood Pressure Control

Add a thiazide diuretic (such as hydrochlorothiazide 12.5 mg daily or indapamide) to the existing lisinopril 40 mg regimen. This combination is the gold-standard, guideline-recommended approach for secondary stroke prevention and has the strongest evidence for reducing recurrent stroke risk.

Primary Recommendation: ACE Inhibitor + Thiazide Diuretic Combination

The 2023 World Stroke Organization guidelines explicitly state that angiotensin-converting enzyme inhibitors combined with a thiazide diuretic are favored in patients with ischemic stroke or TIA, regardless of whether they have a formal diagnosis of hypertension. 1 This combination demonstrated a 43% reduction in recurrent stroke in the landmark PROGRESS trial, even in patients who were not hypertensive at baseline. 2

• The target blood pressure for post-stroke patients is <130/80 mmHg across all resource settings (minimal, essential, and advanced). 1

• Since the patient is already on lisinopril 40 mg (the maximum recommended dose for hypertension per FDA labeling 3), adding a thiazide diuretic is the logical next step rather than switching agents. 2, 3

Specific Thiazide Options

• Hydrochlorothiazide 12.5 mg daily is the FDA-recommended starting dose when added to lisinopril for uncontrolled hypertension. 3

• Indapamide is an alternative thiazide-like diuretic that was specifically used in the PROGRESS trial demonstrating stroke reduction. 2

Alternative Second-Line Agent: Dihydropyridine Calcium Channel Blocker

If the ACE inhibitor + thiazide combination fails to achieve target blood pressure or if there are contraindications to thiazides (such as gout or severe hyponatremia), add a dihydropyridine calcium channel blocker such as amlodipine 5-10 mg daily. 2

• Calcium channel blockers are effective in reducing stroke risk and are well-tolerated in patients with renal impairment. 2

• The 2023 guidelines list thiazide diuretics, ACE inhibitors, and angiotensin II receptor blockers as acceptable options, with calcium channel blockers as reasonable alternatives. 1

Agents to Avoid or Use Only with Specific Indications

• Beta-blockers should only be used if the patient has concurrent ischemic heart disease (such as prior myocardial infarction or stable angina). 1 They are not preferred for stroke prevention alone. 2

• Angiotensin receptor blockers (ARBs) are acceptable alternatives to ACE inhibitors but should not be added on top of an ACE inhibitor due to increased risk of hyperkalemia and renal dysfunction. 1

Monitoring Requirements

• Check serum creatinine and potassium within 1-2 weeks of adding the thiazide diuretic, as the combination of ACE inhibitor + diuretic can affect electrolytes and renal function. 2

• Most stroke patients require two or more antihypertensive agents to achieve the target blood pressure of <130/80 mmHg. 2

• Blood pressure should be measured at every clinical encounter and at least monthly until the target is achieved. 4

Critical Timing Consideration

Since the patient had a "recent" ischemic stroke, ensure that the acute permissive hypertension window (first 48-72 hours) has passed before intensifying antihypertensive therapy. 4 After 48-72 hours, antihypertensive medications should be initiated or restarted in neurologically stable patients with BP ≥140/90 mmHg. 4

Common Pitfalls to Avoid

• Do not add a second ACE inhibitor or combine an ACE inhibitor with an ARB, as this increases adverse events without additional benefit. 2

• Do not use sublingual nifedipine, as it causes unpredictable, precipitous blood pressure drops that may compromise cerebral perfusion. 4

• Avoid alpha-blockers as second-line agents; they should only be used if other medications fail to achieve blood pressure control. 2