Is Losartan (an angiotensin II receptor antagonist) a suitable first-line treatment option for a patient with newly diagnosed hypertension, particularly those with a history of diabetes, kidney disease, or heart failure?

Losartan as First-Line Hypertension Treatment

Losartan (an ARB) is an appropriate first-line treatment option for hypertension, particularly in patients with diabetes and albuminuria, chronic kidney disease, heart failure, or coronary artery disease, but thiazide diuretics remain the preferred initial agent for uncomplicated hypertension based on the strongest cardiovascular outcome evidence. 1, 2

General First-Line Recommendations

The American College of Cardiology identifies four equally acceptable first-line medication classes for hypertension: thiazide or thiazide-like diuretics, ACE inhibitors, ARBs (including losartan), or dihydropyridine calcium channel blockers. 1 However, thiazide diuretics, especially chlorthalidone, have the strongest evidence for preventing cardiovascular events and are considered optimal first-line therapy for uncomplicated hypertension. 2

• All four classes effectively lower blood pressure and reduce cardiovascular morbidity and mortality. 3, 1
• The FDA label confirms losartan is indicated for hypertension treatment in adults and pediatric patients ≥6 years, with proven efficacy in lowering blood pressure and reducing cardiovascular risk. 4
• Most patients require multiple medications to achieve blood pressure targets, so initial drug selection should consider future combination therapy needs. 3

When Losartan Should Be First-Line

Losartan and other ARBs are mandatory first-line therapy in specific high-risk populations:

Diabetes with Albuminuria

• For patients with diabetes and albuminuria (UACR ≥300 mg/g), ACE inhibitors or ARBs are strongly recommended as first-line therapy. 3, 1
• The RENAAL study demonstrated that losartan reduces progression of diabetic nephropathy, decreases doubling of serum creatinine, and reduces end-stage renal disease in type 2 diabetic patients with proteinuria. 3, 4
• Losartan reduces hospitalization for heart failure in diabetic patients with nephropathy. 3

Chronic Kidney Disease

• For any patient with albuminuria (UACR ≥30 mg/g), ACE inhibitors or ARBs are mandatory first-line therapy to reduce proteinuria and slow kidney disease progression. 1, 2
• Evidence favors ACE inhibitors or ARBs over other medication classes for improvement of renal outcomes in non-dialysis-dependent CKD patients, particularly those with albuminuria. 3

Heart Failure

• For patients with heart failure (preserved or reduced ejection fraction), ACE inhibitors or ARBs are recommended for blood pressure control. 3
• ARBs have been shown to reduce major cardiovascular outcomes in patients with heart failure, including diabetic subgroups. 3

Coronary Artery Disease

• For patients with established coronary artery disease, ACE inhibitors or ARBs are recommended as first-line therapy. 1, 2
• ACE inhibitors have demonstrated cardiovascular outcome benefits in high-risk individuals including those with diabetes. 3

Atrial Fibrillation

• ARBs may reduce atrial fibrillation recurrence and should be favored in patients with this comorbidity. 3

Left Ventricular Hypertrophy

• Losartan is specifically indicated to reduce stroke risk in hypertensive patients with left ventricular hypertrophy, though this benefit does not apply to Black patients. 3, 4

When Losartan Should NOT Be First-Line

Uncomplicated Hypertension

• In patients without diabetes, kidney disease, heart failure, or coronary artery disease, thiazide diuretics have superior evidence for preventing cardiovascular events, particularly heart failure. 2
• The ALLHAT study showed no difference in cardiovascular outcomes between chlorthalidone, amlodipine, and lisinopril in patients with eGFR <60 mL/min/1.73 m², but thiazides remain preferred based on broader evidence. 3

Black Patients Without Specific Comorbidities

• Calcium channel blockers or thiazide diuretics are more effective than ACE inhibitors or ARBs when used as monotherapy in Black patients. 1, 2
• However, if albuminuria, diabetes, or CKD is present, ARBs remain first-line regardless of race. 1, 2

Practical Dosing and Monitoring

Dosing Strategy

• Start losartan at 50 mg once daily, with a target dose of 100 mg/day for maximal clinical benefit. 5
• For hypertension with left ventricular hypertrophy, the usual starting dose is 50 mg once daily, increased to 100 mg once daily if needed. 4
• For diabetic nephropathy, start at 50 mg once daily and increase to 100 mg once daily based on blood pressure response. 4
• Consider adding hydrochlorothiazide 12.5 mg if blood pressure remains uncontrolled on losartan monotherapy. 4, 6

Monitoring Requirements

• Monitor serum creatinine and potassium within 7-14 days after initiation, then at least annually. 1
• Follow-up within 7-14 days after medication initiation or dose changes, with goal of achieving blood pressure target within 3 months. 1
• Monitor renal function periodically in patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion. 4

Critical Safety Considerations

Absolute Contraindications

• Never combine losartan with ACE inhibitors due to increased risk of hyperkalemia, acute kidney injury, and syncope without added cardiovascular benefit. 1, 2, 7
• The ONTARGET and NEPHRON-D trials definitively showed dual RAAS blockade increases adverse events without improving outcomes. 3
• Losartan is contraindicated in pregnancy (second and third trimesters cause fetal toxicity, oligohydramnios, and neonatal death). 4

Important Warnings

• Correct volume or salt depletion before initiating losartan to avoid symptomatic hypotension. 4
• Monitor for hyperkalemia, especially when combined with other potassium-sparing agents or in patients with renal impairment. 4
• Continue losartan even as kidney function declines to eGFR <30 mL/min/1.73 m² for cardiovascular benefit, but monitor closely. 1
• Consider withholding or discontinuing therapy if clinically significant decrease in renal function occurs. 4

Combination Therapy Approach

For most patients with confirmed hypertension (BP ≥140/90 mmHg), initial combination therapy with a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker or thiazide-like diuretic is recommended. 1, 7

• Single-pill combinations improve adherence and should be considered. 2, 7
• If blood pressure remains uncontrolled with two drugs, progress to three-drug combination (RAS blocker + calcium channel blocker + thiazide-like diuretic). 1, 7
• For resistant hypertension on three drugs, add a mineralocorticoid receptor antagonist and refer to hypertension specialist. 1, 2

Blood Pressure Targets

• Target <130/80 mmHg for most adults <65 years. 1
• Target systolic BP 120-129 mmHg in most adults if well tolerated. 1, 7
• For diabetic patients, target systolic BP <130 mmHg and diastolic BP <80 mmHg. 3