What is the appropriate initial antihypertensive medication for a patient with stage 1 hypertension and variable blood pressure readings?

Initial Antihypertensive Therapy for Stage 1 Hypertension

Blood Pressure Classification and Treatment Decision

Based on these home readings (averaging approximately 145/87 mmHg), you should initiate pharmacological therapy with a single antihypertensive agent, specifically starting with chlorthalidone 12.5-25 mg once daily as first-line therapy. 1, 2, 3

Confirming the Diagnosis

• These home blood pressure readings confirm Stage 1 hypertension (average >135/85 mmHg on home monitoring), which meets criteria for treatment initiation 2
• Home BP monitoring readings ≥135/85 mmHg are equivalent to office readings ≥140/90 mmHg for diagnosis 2
• The variability in readings (ranging from 126/62 to 169/99 mmHg) is typical and does not change the treatment approach 1

Why Single-Agent Therapy is Appropriate

• For Stage 1 hypertension with BP between 130/80 and 150/90 mmHg, initiation with a single antihypertensive agent is recommended 1, 2
• Two-drug combination therapy is reserved for Stage 2 hypertension (BP >20/10 mmHg above goal or ≥150/90 mmHg) 1, 2
• Since your patient's average BP is approximately 145/87 mmHg, this falls within the single-agent initiation range 1

Specific Medication Recommendation

First-Line Choice: Thiazide-Type Diuretic

Chlorthalidone 12.5-25 mg once daily is the optimal first-line agent based on the following evidence: 2, 3

• Chlorthalidone has the strongest evidence for reducing cardiovascular mortality, heart failure, and stroke compared to other drug classes 3
• It is superior to hydrochlorothiazide for 24-hour BP control, particularly overnight, due to its longer half-life 1, 3
• Network meta-analyses demonstrate diuretics are significantly more effective than calcium channel blockers for preventing heart failure 1, 3
• Chlorthalidone was superior to lisinopril for stroke prevention and superior to amlodipine for heart failure prevention in head-to-head trials 3

Alternative First-Line Options (if thiazide contraindicated or not tolerated)

ACE Inhibitor: Lisinopril 10 mg once daily 2, 4

• Starting dose is 10 mg once daily, with usual maintenance range of 20-40 mg daily 4
• Requires baseline and follow-up monitoring of serum creatinine and potassium within 7-14 days 2

Calcium Channel Blocker: Amlodipine 5 mg once daily 2, 3

• Equally effective as diuretics for all cardiovascular events except heart failure 3
• Does not require laboratory monitoring 2

ARB: Losartan 50 mg once daily 5

• Similar efficacy to ACE inhibitors with potentially better tolerability 5
• Also requires creatinine and potassium monitoring 2

Important Population-Specific Considerations

When NOT to Use Specific Agents

Avoid ACE inhibitors/ARBs if: 2

• History of angioedema
• Pregnancy or planning pregnancy (absolutely contraindicated)
• Severe bilateral renal artery stenosis

Avoid thiazide diuretics if: 2

• Active gout (unless on uric acid-lowering therapy)
• Severe hyponatremia

For Black patients without comorbidities: 1, 3

• Thiazide diuretic or calcium channel blocker are preferred over ACE inhibitors
• ACE inhibitors are 30-36% less effective for stroke and heart failure prevention in this population 3

Monitoring and Follow-Up Strategy

Laboratory Monitoring

If starting chlorthalidone: 2

• Check serum potassium, sodium, and creatinine within 7-14 days
• Maintain potassium >3.5 mmol/L to avoid ventricular arrhythmias 3

If starting ACE inhibitor or ARB: 2

• Check baseline creatinine/eGFR and potassium
• Recheck within 7-14 days to assess for hyperkalemia or acute kidney injury
• Monitor at least annually thereafter 3

Blood Pressure Follow-Up

• Recheck BP in 1 month after initiating therapy 1
• Target BP is <130/80 mmHg for most adults under 65 years 1, 2
• If BP remains uncontrolled after 3 months on optimized single-agent therapy, add a second agent from a different class 2

Titration Strategy if BP Not Controlled

Step 1: Increase chlorthalidone to maximum dose (25 mg daily) before adding second agent 2

Step 2: If still uncontrolled, add either: 1, 2

• ACE inhibitor (lisinopril 10 mg daily), OR
• Calcium channel blocker (amlodipine 5 mg daily)

Step 3: If two drugs insufficient, escalate to three-drug combination (thiazide + ACE inhibitor/ARB + calcium channel blocker) 2

Common Pitfalls to Avoid

• Never combine ACE inhibitor with ARB - this increases adverse events without cardiovascular benefit 2, 3
• Do not delay pharmacotherapy for lifestyle modification trial when BP is ≥140/90 mmHg on home monitoring 2
• Avoid beta-blockers as first-line therapy unless specific indication (heart failure, coronary disease) exists - they are 30-36% less effective than other agents for stroke prevention 3
• Do not use hydrochlorothiazide when chlorthalidone is available - chlorthalidone has superior outcomes data 2, 3
• Ensure proper laboratory follow-up within 7-14 days when starting ACE inhibitors, ARBs, or diuretics to detect electrolyte abnormalities or renal dysfunction 2