Losartan as First-Line Hypertension Treatment

General First-Line Recommendations

The American College of Cardiology recommends four equally acceptable first-line medication classes for hypertension: thiazide or thiazide-like diuretics, ACE inhibitors, ARBs, or dihydropyridine calcium channel blockers 1
Thiazide diuretics 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
Most patients require multiple medications to achieve blood pressure targets, so initial drug selection should consider future combination therapy needs 3, 4

For patients with diabetes and albuminuria, ACE inhibitors or ARBs are strongly recommended as first-line therapy 5, 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 6, 7
Losartan reduces hospitalization for heart failure in diabetic patients with nephropathy 6, 7
For any patient with albuminuria, 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 6, 7
For patients with heart failure, 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 5
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 5
ARBs may reduce atrial fibrillation recurrence and should be favored in patients with this comorbidity 3

Initial combination therapy with a RAS blocker plus either a dihydropyridine calcium channel blocker or thiazide-like diuretic is recommended for most patients with confirmed hypertension 1, 8
Single-pill combinations improve adherence and should be considered 2, 8
If blood pressure remains uncontrolled with two drugs, progress to three-drug combination 1, 8
For resistant hypertension on three drugs, add a mineralocorticoid receptor antagonist and refer to hypertension specialist 1, 2

Never combine losartan with ACE inhibitors due to increased risk of hyperkalemia, acute kidney injury, and syncope without added cardiovascular benefit 1, 2, 8
The ONTARGET and NEPHRON-D trials definitively showed dual RAAS blockade increases adverse events without improving outcomes 6, 7
Continue losartan even as kidney function declines to eGFR <30 mL/min/1.73 m² for cardiovascular benefit, but monitor closely 1