What first‑line antihypertensive should I start for an adult with stage‑2 hypertension, morning systolic blood pressure around 180 mmHg and daytime readings of 140‑160 mmHg?

Initial Antihypertensive Treatment for Stage 2 Hypertension

Start two first-line antihypertensive agents immediately from different drug classes: a thiazide diuretic (chlorthalidone 12.5–25 mg daily preferred over hydrochlorothiazide 25 mg daily) combined with either a long-acting calcium channel blocker (amlodipine 5–10 mg daily) or an ACE inhibitor (lisinopril 10 mg daily). 1, 2

Why Dual Therapy from the Start

Your patient has stage 2 hypertension with morning systolic BP in the 180s, which meets criteria for immediate dual-agent therapy. 1

• The ACC/AHA 2017 guideline explicitly recommends starting two agents simultaneously when BP ≥160/100 mmHg or when BP exceeds target by >20/10 mmHg. 1
• Monotherapy is insufficient in stage 2 hypertension and delays BP control, increasing cardiovascular risk. 2
• For very high BP (SBP ≥180 mmHg), prompt treatment is required to reduce risk of target organ damage. 1

Preferred Drug Combinations

First Choice: Thiazide + Calcium Channel Blocker

• Chlorthalidone 12.5–25 mg once daily + amlodipine 5–10 mg once daily 1, 2
• Chlorthalidone is preferred over hydrochlorothiazide based on longer half-life and proven CVD reduction in the ALLHAT trial. 1, 2
• This combination provides complementary mechanisms: volume reduction plus vasodilation. 1

Alternative: Thiazide + ACE Inhibitor

• Chlorthalidone 12.5–25 mg once daily + lisinopril 10 mg once daily 1, 2
• ACE inhibitors are particularly appropriate if the patient has diabetes, chronic kidney disease, or albuminuria. 1, 3

Alternative: ACE Inhibitor/ARB + Calcium Channel Blocker

• Lisinopril 10 mg daily + amlodipine 5 mg daily, or losartan 50 mg daily + amlodipine 5 mg daily 1, 3, 2
• This combination provides superior renoprotection if kidney disease is present. 3

Race-Specific Considerations

If your patient is Black, prioritize thiazide diuretic + calcium channel blocker over ACE inhibitor/ARB-based regimens as initial therapy. 1, 2

• Black patients typically have low-renin hypertension and respond better to diuretics and CCBs than to ACE inhibitors or ARBs as monotherapy. 2, 4
• However, combination therapy including an ACE inhibitor/ARB with a diuretic or CCB is still effective in Black patients. 2

Target Blood Pressure

Aim for BP <130/80 mmHg in most patients, or <140/90 mmHg if the patient is at lower cardiovascular risk. 1

• The more aggressive target of <130/80 mmHg applies to patients with established cardiovascular disease, diabetes, chronic kidney disease, or 10-year ASCVD risk ≥10%. 1

Monitoring Schedule

Reassess BP within 1 month after initiating therapy. 1, 2

Check serum electrolytes (sodium, potassium) and renal function (creatinine, eGFR) at 2–4 weeks after starting therapy. 1, 3, 2

• This is critical when using ACE inhibitors, ARBs, or thiazide diuretics to detect hyperkalemia, hypokalemia, hyponatremia, or acute kidney injury. 1, 3
• A modest rise in creatinine up to 30% from baseline is acceptable with ACE inhibitors/ARBs and reflects hemodynamic changes. 3

Dose Titration Strategy

If BP remains above target at the 1-month follow-up, increase doses of both agents to their maximum recommended doses before adding a third agent. 1, 2

Do not wait longer than 1 month between dose adjustments in uncontrolled stage 2 hypertension. 1, 3

If BP remains uncontrolled on two maximized agents, add a third first-line drug from a different class (typically the one not yet used from thiazide/CCB/ACE inhibitor-ARB). 1, 3

Critical Pitfalls to Avoid

Never combine an ACE inhibitor with an ARB—this increases risk of hyperkalemia, hypotension, and acute kidney injury without additional cardiovascular benefit. 1, 3, 2

Avoid beta-blockers as first-line therapy unless specific comorbidities exist (heart failure, post-MI, angina), as they are less effective than other first-line agents for stroke prevention. 2

Do not use clonidine as initial therapy—it is a last-line agent reserved for resistant hypertension after failure of multiple first-line drugs due to significant CNS side effects (drowsiness, dizziness, orthostatic hypotension) and risk of rebound hypertensive crisis if abruptly discontinued. 2

Avoid rapid BP reduction in asymptomatic severe hypertension—your patient's daytime readings of 140–160 mmHg suggest chronic hypertension without acute end-organ damage, so gradual reduction over weeks is appropriate. 5, 6

Do not use short-acting nifedipine, which causes unpredictable BP drops and reflex tachycardia. 5

Morning Hypertension Pattern

The morning BP surge to 180s with lower daytime readings suggests inadequate 24-hour BP control. 1

• Once-daily dosing of long-acting agents (chlorthalidone, amlodipine, lisinopril) provides 24-hour coverage and should address morning hypertension. 1, 2
• Consider taking medications in the evening if morning hypertension persists despite adequate dosing, though this requires individualized assessment. 1

When to Consider Hospitalization

If your patient has symptoms of acute end-organ damage (chest pain, dyspnea, neurological deficits, severe headache, visual changes), this is a hypertensive emergency requiring immediate IV therapy in an ICU setting. 5, 6

Asymptomatic severe hypertension (even with SBP 180s) without acute end-organ damage is managed as an outpatient with oral agents as described above. 5, 6