What is the recommended first-line therapy for hypertension in older adults using thiazide diuretics?

Thiazide Diuretics as First-Line Therapy for Hypertension in Older Adults

Thiazide-type diuretics, specifically chlorthalidone, are the recommended first-line therapy for hypertension in older adults without compelling indications for alternative agents. 1

Preferred Thiazide Agent Selection

Chlorthalidone is superior to hydrochlorothiazide (HCTZ) and should be the preferred thiazide diuretic. 1

• Chlorthalidone has more cardiovascular disease risk reduction data than HCTZ, with evidence from landmark trials involving over 50,000 patients 1
• Chlorthalidone lowers blood pressure more effectively than HCTZ, particularly at night, due to its much longer therapeutic half-life 1
• The ACC/AHA guidelines specifically indicate a preference for chlorthalidone because it was the diuretic used in many landmark event-based randomized clinical trials 1
• If chlorthalidone is unavailable, HCTZ (possibly combined with amiloride or triamterene) is a reasonable alternative 2

Evidence for Efficacy in Older Adults

Thiazide diuretics have the strongest evidence for reducing mortality and cardiovascular events in older adults. 1, 3

• Compared with placebo, low-dose thiazide diuretics prevent approximately 2-3 deaths and 2 strokes per 100 patients treated for 4-5 years 2
• Thiazide diuretics are significantly more effective than beta blockers for stroke prevention (30% lower risk) 1
• Thiazide diuretics are significantly better than calcium channel blockers for preventing heart failure 1
• In the ALLHAT trial, chlorthalidone was superior to the ACE inhibitor lisinopril in preventing stroke and superior to the calcium channel blocker amlodipine in preventing heart failure 2

Dosing Strategy for Older Adults

Start with low-dose thiazide therapy and titrate gradually. 4, 3

• Low-dose regimens are safer than high-dose regimens in older adults 3
• Begin at low doses and proceed gradually to minimize adverse effects while maintaining efficacy in decreasing stroke and cardiovascular events 4
• Target blood pressure is <130/80 mmHg for most older adults, or <140/90 mmHg as an initial target per ESC/ESH guidelines 1

When to Use Combination Therapy

For stage 2 hypertension (BP ≥140/90 mmHg and >20/10 mmHg above target), initiate two first-line agents simultaneously. 1, 5

• Preferred combinations include thiazide diuretic + ACE inhibitor/ARB, or thiazide diuretic + calcium channel blocker 5
• For stage 1 hypertension, monotherapy with a thiazide diuretic is reasonable, with sequential addition of other agents if target BP is not achieved 1
• Single-pill combinations improve adherence but may contain lower-than-optimal doses of the thiazide component 1

Population-Specific Modifications

For Black older adults, thiazide diuretics or calcium channel blockers are the best initial choices. 1, 5

• ACE inhibitors and ARBs are notably less effective than calcium channel blockers in preventing heart failure and stroke in Black patients 1
• Initial therapy should include a thiazide diuretic or calcium channel blocker, either alone or in combination 1, 5

For older adults with chronic kidney disease and albuminuria, ACE inhibitors or ARBs should be first-line instead of thiazides. 5

For older adults with coronary artery disease, ACE inhibitors or ARBs are preferred over thiazides. 6, 5

Critical Contraindications and Cautions

Avoid thiazide diuretics in patients with a history of gout. 3

• A history of gout increases the risk of adverse events with thiazide therapy 3
• Thiazides can provoke hyperglycemia and diabetes, though this does not reduce their efficacy in preventing cardiovascular events 2

Monitor serum creatinine, eGFR, and potassium within 7-14 days of initiation and at least annually thereafter. 5

Common Pitfalls to Avoid

• Do not use high-dose thiazide regimens in older adults; low-dose therapy is equally effective and safer 3
• Do not underdose before adding additional agents; ensure adequate titration of the thiazide diuretic first 5
• Do not use HCTZ when chlorthalidone is available, as chlorthalidone has superior evidence and efficacy 1
• Do not overlook orthostatic hypotension assessment in older adults when initiating therapy 7