What types of diuretics are used to manage hypertension?

Types of Diuretics for Blood Pressure Management

Thiazide and thiazide-like diuretics are the preferred first-line diuretic agents for managing hypertension due to their proven efficacy in reducing cardiovascular morbidity and mortality.

First-Line Diuretic Options

Thiazide and Thiazide-Like Diuretics

• Thiazide-type diuretics:

  • Hydrochlorothiazide (HCTZ): Most commonly prescribed, typically dosed at 12.5-25 mg daily 1, 2
  • Often combined with potassium-sparing diuretics (triamterene, amiloride) to reduce hypokalemia risk 1

• Thiazide-like diuretics:

  • Chlorthalidone: Longer half-life (40-60 hours), more potent at equivalent doses compared to HCTZ 3
  • Indapamide: Another long-acting option 4

Chlorthalidone is often preferred over hydrochlorothiazide due to its longer duration of action and superior efficacy, particularly for overnight blood pressure reduction 1, 3. A meta-analysis showed that thiazide-like diuretics resulted in a 12% additional risk reduction for cardiovascular events and a 21% additional risk reduction for heart failure compared to thiazide-type diuretics 5.

Second-Line Diuretic Options

Loop Diuretics

• Furosemide, bumetanide, torsemide
• Not recommended as first-line therapy for hypertension due to lack of outcome data 3
• Reserved for:
  • Patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73m²) 1
  • Heart failure with fluid overload 1
  • Patients on vasodilator drugs with significant fluid retention 3

Potassium-Sparing Diuretics

• Spironolactone, eplerenone (aldosterone antagonists)
• Amiloride, triamterene (epithelial sodium channel blockers)
• Used primarily:
  • In combination with thiazides to reduce hypokalemia 1
  • As add-on therapy for resistant hypertension 6

Efficacy and Evidence

Thiazide diuretics have been the foundation of antihypertensive therapy in most major clinical trials demonstrating reduction in cardiovascular events 1. Meta-analyses of clinical trials have not demonstrated superiority of any drug class compared to thiazide or thiazide-like diuretics for prevention of cardiovascular disease 1.

The ALLHAT trial, one of the largest hypertension trials, showed that chlorthalidone was as effective as amlodipine (CCB) and lisinopril (ACEI) for the primary outcome of coronary heart disease, with chlorthalidone showing superiority in preventing heart failure compared to amlodipine and better stroke prevention compared to lisinopril 3, 4.

Dosing Considerations

• Low-dose thiazide therapy (hydrochlorothiazide 12.5 mg or chlorthalidone 12.5-15 mg) is often sufficient and minimizes adverse effects 7
• Once-daily dosing is typically effective due to long half-lives, especially with chlorthalidone 3
• When initiating therapy, electrolytes and kidney function should be checked within 2-4 weeks 1, 6

Special Populations

• Black patients: Thiazide diuretics and calcium channel blockers are more effective than beta-blockers and renin-angiotensin system inhibitors 1
• Elderly patients: Thiazide diuretics have demonstrated benefit in reducing cardiovascular events in older adults, including those with isolated systolic hypertension 1
• Chronic kidney disease: Thiazide diuretics can be effective even in advanced CKD, though chlorthalidone is preferred 1
• Diabetes: While thiazides can affect glucose metabolism, their cardiovascular benefits outweigh these concerns 4

Common Pitfalls and Caveats

1. Underutilization: Despite strong evidence supporting their use, thiazide diuretics remain underutilized in clinical practice 1

2. Metabolic effects: Monitor for:

   • Hypokalemia (can increase glucose intolerance)
   • Hyponatremia (especially in elderly)
   • Hyperuricemia
   • Hypercalcemia 3

3. Drug interactions: NSAIDs can blunt the effectiveness of thiazide diuretics 3

4. Inappropriate discontinuation: Thiazide diuretics should not automatically be discontinued when eGFR decreases to <30 mL/min/1.73 m², as they may still be effective 1

5. Combination therapy: Most patients will require multiple agents to achieve BP goals. When BP is >20/10 mmHg above goal, consider initiating with two drugs, one being a thiazide diuretic 1

By following these evidence-based recommendations for diuretic selection in hypertension management, clinicians can effectively reduce cardiovascular morbidity and mortality while minimizing adverse effects.