What is the optimal first‑line antihypertensive medication for a patient aged 65 years or older with primary hypertension?

Best Medication for Hypertension in Geriatric Patients

Thiazide-type diuretics, especially chlorthalidone, are the preferred first-line antihypertensive agents for patients aged 65 years or older with primary hypertension. 1, 2

First-Line Agent: Thiazide-Type Diuretics

• Chlorthalidone 12.5–25 mg once daily is the optimal choice because it demonstrates superior cardiovascular outcomes compared to other antihypertensive classes, particularly for preventing heart failure and stroke in older adults. 1, 2

• Chlorthalidone outperforms hydrochlorothiazide due to its longer half-life (40–60 hours vs. 6–12 hours), providing superior 24-hour blood pressure control and better overnight blood pressure reduction. 2, 3

• In the landmark ALLHAT trial, chlorthalidone was superior to amlodipine for preventing heart failure (38% lower rate) and superior to lisinopril for preventing both heart failure (19% lower rate) and stroke (15% lower rate). 1, 2

• Thiazide diuretics are particularly effective in elderly patients because this population typically has low-renin, volume-dependent hypertension and isolated systolic hypertension—the predominant form after age 65. 4, 5

• Low-dose thiazide regimens (chlorthalidone 12.5–25 mg or hydrochlorothiazide 25 mg) are safer than high-dose regimens, minimizing metabolic side effects while maintaining efficacy. 6, 7

Alternative First-Line Agent: Calcium Channel Blockers

• Long-acting dihydropyridine calcium channel blockers (amlodipine 5–10 mg daily) are an acceptable first-line alternative when thiazides are not tolerated or contraindicated. 1, 4

• Calcium channel blockers achieve comparable reductions in most cardiovascular events to thiazides but are less effective for heart failure prevention. 1, 2

• For Black elderly patients specifically, calcium channel blockers or thiazide diuretics should be chosen over ACE inhibitors or ARBs as first-line therapy. 1

ACE Inhibitors and ARBs: Second-Tier Options

• ACE inhibitors and ARBs may be used as first-line therapy but are less effective than thiazides and calcium channel blockers for stroke prevention in older adults. 1, 2

• These agents are preferred when specific comorbidities exist: heart failure with reduced ejection fraction, chronic kidney disease with proteinuria, diabetes with albuminuria, or post-myocardial infarction. 1, 2

Beta-Blockers: Avoid as First-Line

• Beta-blockers should NOT be used as first-line therapy in elderly patients without compelling indications (heart failure, coronary artery disease, atrial fibrillation) because they are 30–36% less effective than thiazides and calcium channel blockers for preventing stroke and major cardiovascular events. 1, 2

Blood Pressure Targets for Geriatric Patients

• For community-dwelling adults aged 65–75 years, target systolic blood pressure <130 mmHg (minimum acceptable <140 mmHg). 1, 2

• For adults ≥75 years or those with high comorbidity burden and limited life expectancy, a more conservative target of <140/90 mmHg may be appropriate, guided by clinical judgment and frailty assessment. 1

• The SPRINT trial demonstrated that intensive blood pressure control (systolic <120 mmHg) in adults ≥75 years reduced cardiovascular events by 34% and all-cause mortality, even in frail participants, without increasing serious adverse events. 1, 2

Combination Therapy Strategy

• For stage 1 hypertension (130–139/80–89 mmHg), start with monotherapy (thiazide, calcium channel blocker, or ACE inhibitor/ARB) and titrate as needed. 1, 2

• For stage 2 hypertension (≥140/90 mmHg or >20/10 mmHg above target), initiate two agents from different classes simultaneously, either as separate pills or fixed-dose combination. 1, 2

• The preferred triple-therapy combination is: thiazide diuretic + calcium channel blocker + ACE inhibitor or ARB. 1, 2

Critical Monitoring and Safety Considerations

• Check serum potassium and creatinine 2–4 weeks after initiating thiazide therapy to detect hypokalemia or renal function changes. 2

• Assess for orthostatic hypotension by measuring blood pressure in both sitting and standing positions in all older adults, as intensive blood pressure lowering increases this risk modestly. 1, 2

• Start at low doses and titrate gradually in elderly patients, especially when initiating two drugs simultaneously. 1, 5

Common Pitfalls to Avoid

• Do NOT withhold antihypertensive treatment solely because of advanced age; evidence supports aggressive management even in patients >80 years. 1, 2

• Do NOT use alpha-blockers as first-line therapy—they are inferior to thiazides for cardiovascular disease prevention. 1, 2

• Do NOT combine an ACE inhibitor with an ARB (dual renin-angiotensin blockade), as this increases adverse events without added benefit. 1, 2

• Do NOT assume isolated systolic hypertension requires less aggressive treatment—it is the predominant and most dangerous form in the elderly and should be the primary therapeutic target. 1, 2

• Avoid high-dose thiazide regimens; low doses (chlorthalidone 12.5–25 mg or hydrochlorothiazide 25 mg) provide optimal efficacy with minimal metabolic side effects. 6, 7