Angiotensin Receptor Blockers (ARBs): Commonly Used Agents, Dosing, and Safety
Commonly Used ARB Agents
Seven ARBs are FDA-approved and widely used in clinical practice: candesartan, eprosartan, irbesartan, losartan, telmisartan, olmesartan, and valsartan. 1, 2, 3
These agents share a common mechanism—selective blockade of the angiotensin type 1 (AT1) receptor—which prevents vasoconstriction, sodium retention, aldosterone secretion, and cardiac/vascular hypertrophy regardless of whether angiotensin II is produced systemically or locally via ACE- or non-ACE pathways. 2, 4
Starting Doses and Target Dose Ranges
Losartan
- Starting dose: 50 mg once daily 5
- Target dose for hypertension: 100 mg once daily 5
- Target dose for heart failure: 100–150 mg once daily; the HEAAL trial demonstrated that 150 mg daily was superior to 50 mg daily with a 10% relative risk reduction in death or heart failure hospitalization 5
- Frequency: Can be given once daily or divided into twice-daily dosing (e.g., 50 mg BID) 5
Valsartan
- Starting dose for hypertension: 80–160 mg once daily 6
- Dose range for hypertension: 80–320 mg once daily 6
- Starting dose for heart failure: 40 mg twice daily, uptitrated to 80 mg and 160 mg twice daily as tolerated 6
- Post-MI dosing: Start 20 mg twice daily as early as 12 hours after MI, uptitrate to target of 160 mg twice daily 6
Candesartan
- Starting dose: 8 mg once daily 5
- Target dose: 16–32 mg once daily 5
- Candesartan improved outcomes in heart failure patients intolerant of ACE inhibitors in the CHARM trials 1
Telmisartan
- Starting dose for hypertension: 40 mg once daily 7
- Dose range: 40–80 mg once daily 7
- For cardiovascular risk reduction: 80 mg once daily 7
Irbesartan
- Dose range: 50–100 mg once daily 5
- Demonstrated renal protection in diabetic nephropathy in the IDNT trial 5
Titration and Monitoring
Titration schedule: Adjust doses no more frequently than every 2 weeks to reach target or maximally tolerated doses. 1
Blood pressure reassessment: Check office BP every 2–4 weeks during titration, aiming to reach target (<130/80 mmHg for most adults) within 3 months. 5
Laboratory monitoring: Measure serum creatinine/eGFR and potassium within 1–2 weeks after initiating therapy or increasing doses, then at least annually during maintenance. 1, 5 Patients with chronic kidney disease, diabetes, low baseline sodium, or systolic BP <80 mmHg require particularly close surveillance. 1
Main Safety Considerations
Hypotension
ARBs produce dose-dependent blood pressure reduction and can cause symptomatic hypotension, especially in volume-depleted patients or those with systolic BP <80 mmHg at baseline. 1 Measure blood pressure in both sitting and standing positions in elderly patients to detect orthostatic changes. 5
Hyperkalemia
ARBs suppress aldosterone secretion and increase the risk of hyperkalemia, particularly when combined with potassium-sparing diuretics, potassium supplements, or in patients with renal impairment or diabetes. 1, 5 Monitor potassium closely after initiation and dose changes. 1
Renal Dysfunction
ARBs can worsen renal function, especially in patients with bilateral renal artery stenosis, severe heart failure, or pre-existing renal impairment. 1 A modest creatinine rise of 0.1–0.3 mg/dL is expected and does not require discontinuation unless acute tubular necrosis is evident. 5
Angioedema
Although much less frequent than with ACE inhibitors, angioedema can occur with ARBs. 1 Cases have been reported in patients who previously developed angioedema to ACE inhibitors, so extreme caution is required when substituting an ARB in this population. 1, 5
Pregnancy
ARBs are absolutely contraindicated in all trimesters of pregnancy due to serious fetal toxicity including renal dysfunction, oligohydramnios, skull hypoplasia, and fetal death. 5 Discontinue immediately upon pregnancy detection and switch to pregnancy-compatible agents such as methyldopa, labetalol, or nifedipine. 5
Critical Contraindications
Never combine ARBs with ACE inhibitors or direct renin inhibitors (aliskiren). Dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without providing additional cardiovascular benefit. 1, 5 The VALIANT trial demonstrated that combining an ACE inhibitor with an ARB increased adverse outcomes. 1, 5
Do not combine ARBs with aldosterone antagonists and ACE inhibitors simultaneously. The routine triple combination of all three renin-angiotensin system inhibitors cannot be recommended due to markedly increased risks of renal dysfunction and hyperkalemia. 1
Combination Therapy
When BP remains uncontrolled on ARB monotherapy at maximum dose (e.g., losartan 100 mg), add hydrochlorothiazide 12.5–25 mg daily rather than exceeding the maximum ARB dose. 5 The combination provides additive blood pressure lowering and improves adherence when given as a single-pill fixed-dose combination. 5
Alternative second-line agents include dihydropyridine calcium channel blockers (e.g., amlodipine 5–10 mg daily). 5 For resistant hypertension on triple therapy (ARB + diuretic + CCB), add spironolactone 25 mg daily as the fourth agent. 5
Special Populations
Elderly patients (≥75 years): Initiate at low doses and titrate slowly with small increments every 1–2 weeks, monitoring closely for dizziness, falls, and orthostatic hypotension. 5
Hepatic impairment: For losartan, start at 25 mg once daily due to a 5-fold increase in plasma concentrations. 5
Chronic kidney disease: ARBs can be continued as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit, but require more frequent monitoring of potassium and creatinine. 5
Common Pitfalls to Avoid
Underdosing is widespread: Less than 25% of patients are ever titrated to target doses in clinical practice, yet higher doses provide greater benefits than lower doses with little evidence that medium-range doses approximate the benefits of target doses. 5
Do not stop ARBs prematurely for mild hyperkalemia: Implement potassium-lowering strategies (dietary restriction, discontinue potassium supplements, add loop diuretics) before discontinuing the ARB. 5
Do not assume medication discontinuation was due to side effects: Patients often stop drugs because of cost, access issues, or misunderstanding; direct questioning is required before escalating therapy. 5