What is the recommended initial antihypertensive medication for a 59-year-old female patient with stage 2 hypertension (blood pressure 162/92 mmHg)?

Initial Antihypertensive Medication for Stage 2 Hypertension

For this 59-year-old female with stage 2 hypertension (162/92 mmHg), start combination therapy immediately with two first-line agents: a thiazide diuretic (chlorthalidone 12.5-25 mg daily) plus either an ACE inhibitor (lisinopril 10 mg daily) or a calcium channel blocker (amlodipine 5 mg daily), preferably as a single-pill combination. 1, 2

Rationale for Combination Therapy

• Stage 2 hypertension (BP >20/10 mmHg above target of <130/80 mmHg) requires initiation with two antihypertensive agents to achieve more rapid BP control and reduce cardiovascular risk 1, 2

• Single-pill combinations are strongly preferred over separate pills because they improve adherence and persistence with therapy 1, 2

• Most patients with hypertension require multiple agents for adequate BP control, and starting with combination therapy achieves target BP faster 1

Specific Medication Recommendations

First Choice: Thiazide Diuretic + ACE Inhibitor or ARB

• Chlorthalidone 12.5-25 mg daily is the preferred thiazide diuretic based on superior outcomes data compared to hydrochlorothiazide, particularly for preventing heart failure and stroke 1, 2

• Lisinopril 10 mg daily is an appropriate ACE inhibitor starting dose for combination therapy 3

• Alternatively, an ARB like losartan 50 mg daily can be used if ACE inhibitors cause cough 2, 4

Alternative First Choice: Thiazide Diuretic + Calcium Channel Blocker

• Amlodipine 5 mg daily combined with chlorthalidone is equally effective and may be preferred in certain patients 1, 2

• This combination showed excellent cardiovascular outcomes in major trials, with CCBs being particularly effective for isolated systolic hypertension 2

Why These Specific Agents

Thiazide diuretics (especially chlorthalidone) are the cornerstone of initial therapy because:

• They demonstrated superiority over ACE inhibitors for stroke prevention and over CCBs for heart failure prevention in the largest head-to-head trial (ALLHAT) 1, 2
• High-quality evidence shows reduction in all-cause mortality, stroke, and cardiac events when treating BP from 160 mmHg to <150 mmHg 1
• They are cost-effective and have decades of proven cardiovascular benefit 1, 5

ACE inhibitors or ARBs are appropriate second agents because:

• They provide complementary mechanisms of action with diuretics 1
• They reduce cardiovascular events and are well-tolerated in most patients 2, 5
• ARBs may be better tolerated than ACE inhibitors due to lower incidence of cough 2

Calcium channel blockers (dihydropyridines) are equally valid alternatives because:

• They are as effective as diuretics for reducing all cardiovascular events except heart failure 1, 2
• They are particularly effective for older adults and those with isolated systolic hypertension 2
• The combination of CCB + diuretic is highly effective 1

Age and Sex Considerations

• At age 59, this patient should be treated to a target BP <130/80 mmHg based on current ACC/AHA guidelines 1, 2

• Women are well-represented in hypertension trials and benefit equally from treatment, with stroke reduction being a primary benefit 1

• The recommendation to treat to <140 mmHg (rather than <150 mmHg) is particularly important for women to prevent excess cardiovascular risk 1

What NOT to Use

• Do not use beta-blockers as first-line therapy unless she has coronary artery disease or heart failure, as they are significantly less effective than diuretics for stroke prevention 1, 2

• Do not use alpha-blockers as first-line therapy because they are less effective for CVD prevention than thiazide diuretics 1, 2

• Do not combine two RAS blockers (ACE inhibitor + ARB) as this combination is not recommended 1

Practical Implementation

Starting regimen options:

1. Chlorthalidone 12.5 mg + lisinopril 10 mg daily (single-pill combination if available) 1, 2, 3

2. Chlorthalidone 12.5 mg + amlodipine 5 mg daily (single-pill combination if available) 1, 2

3. If chlorthalidone is unavailable, hydrochlorothiazide 12.5-25 mg can substitute, though it is less potent 1, 5

Follow-up plan:

• Recheck BP in 2-4 weeks to assess response 2
• Target BP is <130/80 mmHg 1, 2
• If BP remains uncontrolled, increase doses or add a third agent from a different class 1
• Monitor for electrolyte abnormalities (particularly potassium and sodium) with diuretic therapy 2

Common Pitfalls to Avoid

• Do not start with monotherapy in stage 2 hypertension (BP >160/100 mmHg or >20/10 mmHg above target), as this delays achieving BP control 1

• Do not use separate pills when single-pill combinations are available, as adherence is significantly better with single-pill combinations 1

• Do not ignore the diastolic BP of 92 mmHg - while systolic BP is the primary driver of cardiovascular risk at this age, both values need treatment 1

• Do not delay treatment initiation - high-quality evidence shows that treating BP from 160 mmHg to <150 mmHg reduces mortality by 10%, stroke by 26%, and cardiac events by 23% 1