What medications are used to treat high blood pressure (hypertension) and associated swelling (edema)?

Medications for Blood Pressure and Swelling

For hypertension with associated edema, initiate combination therapy with a thiazide diuretic (hydrochlorothiazide 12.5-25 mg or chlorthalidone 12.5-25 mg daily) plus an ACE inhibitor (such as lisinopril) or ARB (such as losartan), as this addresses both blood pressure control and fluid retention while reducing cardiovascular morbidity and mortality. 1

First-Line Medication Strategy

Diuretics as Foundation

• Thiazide or thiazide-like diuretics are the cornerstone for treating both hypertension and edema, with chlorthalidone 12.5-25 mg or hydrochlorothiazide 12.5-25 mg daily as preferred initial doses 1
• Chlorthalidone demonstrated superior outcomes in the ALLHAT trial, reducing heart failure risk more effectively than amlodipine or lisinopril 1
• Diuretics are the only antihypertensive class that adequately controls fluid retention, making them essential when edema is present 1
• Low-dose formulations (12.5-25 mg) provide equivalent blood pressure reduction to higher doses while minimizing metabolic side effects like hypokalemia and hyperglycemia 1, 2, 3

Combination Therapy Approach

• Most patients with confirmed hypertension (BP ≥140/90 mmHg) should start with two-drug combination therapy rather than monotherapy for more effective blood pressure control 1
• The preferred combination is a RAS blocker (ACE inhibitor or ARB) with either a dihydropyridine calcium channel blocker or a thiazide diuretic 1
• Fixed-dose single-pill combinations improve adherence and should be used when available 1

Specific Medication Options

ACE Inhibitors

• Lisinopril is indicated for hypertension treatment and can be combined with hydrochlorothiazide in fixed-dose combinations (10/12.5 mg, 20/12.5 mg, or 20/25 mg) 1, 4
• ACE inhibitors reduce cardiovascular mortality and stroke risk when combined with diuretics 1, 5
• Monitor for hyperkalemia, especially when combined with potassium-sparing diuretics 1

Angiotensin Receptor Blockers (ARBs)

• Losartan can be combined with hydrochlorothiazide in fixed-dose formulations (50/12.5 mg or 100/25 mg) 1, 6
• ARBs are appropriate alternatives to ACE inhibitors with similar cardiovascular benefits 1
• Do not combine two RAS blockers (ACE inhibitor plus ARB) as this increases adverse effects without additional benefit 1, 7

Calcium Channel Blockers

• Amlodipine can be added as third-line therapy if blood pressure remains uncontrolled on ACE inhibitor/ARB plus diuretic 1
• Dihydropyridine CCBs (like amlodipine) are preferred; avoid non-dihydropyridines (verapamil, diltiazem) in heart failure with reduced ejection fraction 1

Treatment Titration Algorithm

Step 1: Initial Therapy

• Start with ACE inhibitor or ARB plus thiazide diuretic combination 1
• Target blood pressure: <130/80 mmHg for most adults, with systolic 120-129 mmHg optimal if tolerated 1

Step 2: If Uncontrolled After 2-4 Weeks

• Increase to three-drug combination: RAS blocker + dihydropyridine CCB + thiazide diuretic, preferably as single-pill combination 1

Step 3: Resistant Hypertension (Still Uncontrolled)

• Add spironolactone 25 mg daily if serum potassium <4.5 mmol/L and eGFR >45 mL/min/1.73m² 7
• Monitor potassium and renal function 1-2 weeks after initiation 7

Critical Monitoring Parameters

Electrolyte Management

• Check serum potassium before and 1-2 weeks after starting diuretics or RAS blockers 1, 7
• Maintain potassium >3.5 mmol/L, as levels below this threshold negate the cardiovascular benefits of diuretic therapy 1
• Avoid potassium-sparing agents if creatinine ≥2.5 mg/dL (men) or ≥2.0 mg/dL (women), or if potassium ≥5.0 mEq/L 1

Blood Pressure Targets

• Office BP goal: <130/80 mmHg for adults <65 years; systolic <130 mmHg for adults ≥65 years 1
• Confirm with home or ambulatory monitoring to exclude white coat hypertension 7
• Avoid diastolic BP <60 mmHg in patients with coronary artery disease due to risk of myocardial ischemia 1

Edema Assessment

• Diuretic doses should be titrated to control volume overload without causing excessive volume depletion 1
• Inappropriately low diuretic doses result in persistent fluid retention; excessively high doses cause hypotension and renal insufficiency 1

Common Pitfalls to Avoid

• Do not use high-dose thiazides (>50 mg hydrochlorothiazide or >25 mg chlorthalidone) as they provide minimal additional blood pressure reduction but significantly increase metabolic side effects 1
• Avoid NSAIDs in patients on diuretics and RAS blockers due to effects on blood pressure, volume status, and renal function 1
• Do not abruptly discontinue beta-blockers if previously prescribed, as this causes rebound hypertension 7
• Monitor for orthostatic hypotension, especially in elderly patients on multiple antihypertensive agents 7

Special Populations

Heart Failure with Preserved Ejection Fraction (HFpEF)

• Diuretics are mandatory for volume overload symptoms 1
• After volume control, add ACE inhibitor or ARB plus beta-blocker targeting systolic BP <130 mmHg 1

Pregnancy Considerations

• Losartan and lisinopril can cause fetal harm or death and are contraindicated in pregnancy 6, 4
• Discuss alternative antihypertensive options with women of childbearing potential 6