What is a reasonable first-line antihypertensive agent for an adult female with hypertension?

First-Line Antihypertensive Agent for an Adult Female

For an adult female with hypertension and no specific comorbidities, initiate treatment with chlorthalidone 12.5-25 mg once daily as the first-line agent. 1, 2

Rationale for Thiazide-Like Diuretic Selection

The 2017 ACC/AHA guidelines explicitly state that all first-line antihypertensive classes (thiazide diuretics, ACE inhibitors, ARBs, and calcium channel blockers) are useful and effective for hypertension treatment. 1 However, thiazide-type diuretics, particularly chlorthalidone, provide the strongest evidence for reducing cardiovascular mortality, stroke, and heart failure compared to other first-line agents. 2, 3

• Chlorthalidone demonstrated superiority over the ACE inhibitor lisinopril in preventing stroke and over the calcium channel blocker amlodipine in preventing heart failure in the ALLHAT trial involving over 50,000 patients. 2, 3
• Thiazide diuretics reduce all-cause mortality by approximately 2-3 deaths per 100 patients treated over 4-5 years, with similar reductions in stroke incidence. 3
• A 10 mmHg reduction in systolic blood pressure decreases cardiovascular events by 20-30%, and thiazide diuretics achieve this effectively. 4

Sex-Specific Considerations

The ACC/AHA guidelines explicitly state there is no evidence that BP threshold for initiating treatment, treatment target, choice of initial medication, or combination of medications differs for women versus men. 1

• Women may experience slightly higher rates of ACE inhibitor-induced cough and calcium channel blocker-induced edema compared to men, but these differences do not alter first-line drug selection. 1
• Women are more likely to experience hypokalemia and hyponatremia with diuretics, requiring monitoring of electrolytes within 7-14 days of initiation and at least annually thereafter. 1, 2

Alternative First-Line Options

If chlorthalidone is not tolerated or contraindicated, the following alternatives are appropriate:

• Calcium channel blocker (amlodipine 5-10 mg once daily): Equally effective as thiazides for all cardiovascular events except heart failure, and a good alternative when diuretics are not tolerated. 1, 2, 5
• ACE inhibitor (lisinopril 10-40 mg once daily): Effective first-line option, particularly for patients with albuminuria or established coronary artery disease. 2, 6
• ARB (losartan 50-100 mg once daily): Equally effective to ACE inhibitors with better tolerability (less cough and angioedema). 2

Treatment Initiation Strategy Based on Hypertension Stage

For Stage 1 hypertension (130-139/80-89 mmHg):

• Start with single-agent therapy (chlorthalidone preferred) and titrate dosage, then add sequential agents if needed to reach target <130/80 mmHg. 1, 2

For Stage 2 hypertension (≥140/90 mmHg or BP >20/10 mmHg above target):

• Initiate two first-line agents from different classes immediately, preferably as a single-pill combination. 1, 2
• Preferred combinations include: ACE inhibitor/ARB + calcium channel blocker, ACE inhibitor/ARB + thiazide diuretic, or calcium channel blocker + thiazide diuretic. 7, 8

Blood Pressure Target

Target BP <130/80 mmHg for most adults <65 years of age. 1, 2, 4

Critical Monitoring Requirements

• Monitor blood pressure monthly after medication initiation or dose changes until target is achieved, then every 3-5 months once controlled. 1, 2
• For patients on thiazide diuretics, monitor serum creatinine, eGFR, and potassium within 7-14 days of initiation and at least annually thereafter due to risk of hypokalemia and hyponatremia. 2, 7
• Check standing BP in elderly patients to assess for orthostatic hypotension. 2

Common Pitfalls to Avoid

• Do not use beta-blockers as first-line therapy unless there is a compelling indication (e.g., coronary artery disease, heart failure), as they are less effective than thiazide diuretics and calcium channel blockers for stroke prevention. 1
• Never combine ACE inhibitors with ARBs, as this increases adverse effects (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1, 7
• Avoid underdosing medications before adding additional agents—titrate to optimal doses before adding a second drug. 7
• Thiazide diuretics can provoke hyperglycemia and diabetes, but this does not reduce their efficacy in preventing cardiovascular events. 3