A patient with severe hypertension (170/100 mm Hg) on Losartan 100 mg daily who is allergic to amlodipine (calcium‑channel blocker), lisinopril (angiotensin‑converting‑enzyme inhibitor), metoprolol (β‑blocker) and spironolactone (mineralocorticoid‑receptor antagonist) – what is the best next step in treatment?

Optimal Treatment for Severe Hypertension with Multiple Drug Allergies

Add a thiazide-like diuretic (chlorthalidone 12.5–25 mg or indapamide 1.5–2.5 mg daily) immediately to the existing losartan regimen, as this patient lacks the foundational triple therapy required for resistant hypertension and has exhausted most other first-line options due to documented allergies. 1

Rationale for Thiazide-Like Diuretic as Next Step

• The 2024 ESC Guidelines establish that optimal hypertension management requires a combination of an ARB (already on losartan 100 mg), a calcium channel blocker (allergic to amlodipine), and a thiazide/thiazide-like diuretic—this patient is missing the diuretic component entirely. 1

• Thiazide-like diuretics (chlorthalidone or indapamide) are superior to standard thiazides for cardiovascular outcomes and are specifically recommended when building resistant hypertension regimens. 1

• With BP at 170/100 mmHg on monotherapy, this represents uncontrolled stage 2 hypertension requiring immediate intensification to prevent target organ damage. 1

Why Other Options Are Contraindicated or Suboptimal

• Cannot add ACE inhibitor (lisinopril allergy documented): While RAS blockade optimization would normally be prioritized in resistant hypertension 2, the patient already has maximal ARB dosing (losartan 100 mg) and documented ACE inhibitor allergy, making dual RAS blockade both contraindicated and impossible. 1

• Cannot add calcium channel blocker (amlodipine allergy documented): Dihydropyridine CCBs would be the preferred second agent but are unavailable due to allergy. 1

• Cannot add beta-blocker (metoprolol allergy documented): Beta-blockers are fourth-line agents and already contraindicated by allergy. 1

• Cannot add spironolactone (allergy documented): Mineralocorticoid receptor antagonists are reserved for fourth-line therapy after triple therapy optimization. 1

Specific Dosing Algorithm

1. Initiate chlorthalidone 12.5 mg daily (preferred) or indapamide 1.5 mg daily as these thiazide-like agents have longer half-lives and superior cardiovascular outcomes compared to hydrochlorothiazide. 1

2. Uptitrate to chlorthalidone 25 mg or indapamide 2.5 mg after 2–4 weeks if BP remains >130/80 mmHg and the medication is well-tolerated. 1

3. Monitor serum potassium and creatinine at baseline, 1–2 weeks after initiation, and every 3–6 months thereafter, as thiazide-like diuretics can cause hypokalemia and volume depletion. 1

Fourth-Line Options If BP Remains Uncontrolled

If BP remains ≥140/90 mmHg after optimizing losartan plus thiazide-like diuretic:

• Consider eplerenone 25–50 mg daily as an alternative mineralocorticoid receptor antagonist if the spironolactone allergy was due to gynecomastia or other non-life-threatening adverse effects (eplerenone has lower anti-androgenic activity). 1

• Add a centrally acting agent (clonidine 0.1–0.3 mg twice daily or alpha-methyldopa 250–500 mg twice daily) if eplerenone is not an option. 1

• Consider hydralazine 25–100 mg twice daily as a direct vasodilator, though this requires careful monitoring for reflex tachycardia and lupus-like syndrome. 1

• Alpha-blockers (doxazosin 1–8 mg daily) may be considered but are less preferred due to orthostatic hypotension risk. 1

Blood Pressure Targets

• Target BP <130/80 mmHg given the severity of presentation (170/100 mmHg represents significant cardiovascular risk requiring aggressive management). 1

• The 2024 ESC Guidelines recommend treating most patients to systolic BP 120–129 mmHg when tolerated, but initial goal should be <140/90 mmHg, then <130/80 mmHg as treatment is optimized. 1

Critical Monitoring and Pitfalls

• Verify allergy history: Confirm whether documented "allergies" represent true hypersensitivity reactions versus intolerances (e.g., ACE inhibitor cough, beta-blocker fatigue, CCB edema)—if intolerances rather than true allergies, alternative agents within the same class may be trialed under supervision. 1

• Assess for secondary hypertension: Resistant hypertension at this severity warrants screening for primary aldosteronism (aldosterone-to-renin ratio), renovascular disease, obstructive sleep apnea, and medication non-adherence before adding multiple agents. 1

• Avoid volume depletion: When initiating diuretics in patients on ARBs, monitor for symptomatic hypotension, acute kidney injury, and hyperkalemia (though hypokalemia is more common with thiazide-like diuretics alone). 1

• Do not combine ACE inhibitor with ARB: Even if the lisinopril "allergy" is reconsidered, dual RAS blockade increases adverse events without additional benefit and is contraindicated. 2