In a 52‑year‑old man with hypertension on amlodipine 10 mg (max dose) and losartan 100 mg (max dose) whose seated blood pressure remains at stage 2 hypertension (160/100 mm Hg), should I add a thiazide diuretic rather than increase the current agents?

Add a Thiazide Diuretic Immediately

Yes, you should add a thiazide or thiazide-like diuretic as the third agent right now—your patient has stage 2 hypertension (160/100 mmHg) on maximum doses of two medications, and guideline-recommended triple therapy is ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic. 1, 2

Why Add a Diuretic Rather Than Increase Current Medications

• Your patient is already on amlodipine 10 mg (maximum dose) and losartan 100 mg (maximum dose for hypertension), so further dose escalation is not possible. 2

• The 2017 ACC/AHA and ESC 2024 guidelines explicitly state that when blood pressure remains uncontrolled on a two-drug combination of ARB + calcium channel blocker, the next step is adding a thiazide or thiazide-like diuretic to create the evidence-based triple therapy regimen. 1, 2

• All major international guidelines (JNC 8, ESH/ESC, NICE, Taiwan, China) specify that the standard three-drug combination for uncontrolled hypertension is: ARB (or ACE inhibitor) + calcium channel blocker + thiazide diuretic. 1, 2

Which Diuretic to Choose

• Start chlorthalidone 12.5–25 mg once daily in the morning as the preferred thiazide-like diuretic. 2

• Chlorthalidone is superior to hydrochlorothiazide because of its longer duration of action (24–72 hours vs. 6–12 hours) and stronger cardiovascular outcome data from the ALLHAT trial, where it outperformed amlodipine and lisinopril in preventing heart failure. 2

• If chlorthalidone is unavailable, hydrochlorothiazide 25 mg once daily is an acceptable alternative, though it remains inferior to chlorthalidone for 24-hour blood pressure control. 2

Blood Pressure Targets and Monitoring

• Your target is <130/80 mmHg for most patients, with a minimum acceptable goal of <140/90 mmHg. 1, 2

• Reassess blood pressure within 2–4 weeks after adding the diuretic, with the goal of achieving target blood pressure within 3 months of this treatment modification. 1, 2

• Check serum potassium and creatinine 2–4 weeks after initiating the diuretic to detect hypokalemia or changes in renal function, especially important given the concurrent losartan. 1, 2

Critical Steps Before Adding the Diuretic

• Verify medication adherence first—non-adherence is the most common cause of apparent treatment resistance. Use pill counts, pharmacy refill data, or direct questioning. 2

• Review for interfering substances: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, stimulants, and herbal supplements (ephedra, licorice) can all raise blood pressure and should be stopped if present. 2

• Confirm true hypertension with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) to rule out white coat hypertension before escalating therapy. 1, 2

Lifestyle Modifications to Reinforce

• Sodium restriction to <2 g/day (approximately 5 g salt) yields a 5–10 mmHg systolic reduction and enhances the efficacy of all antihypertensive classes, especially diuretics and ARBs. 2

• Weight loss if BMI ≥25 kg/m²—losing approximately 10 kg reduces blood pressure by about 6.0/4.6 mmHg (systolic/diastolic). 2

• DASH dietary pattern (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat) lowers blood pressure by roughly 11.4/5.5 mmHg. 2

• Regular aerobic exercise (≥30 minutes most days, approximately 150 minutes/week moderate intensity) reduces blood pressure by approximately 4/3 mmHg. 2

• Limit alcohol to ≤2 drinks/day for men and ≤1 drink/day for women. 2

If Blood Pressure Remains Uncontrolled on Triple Therapy

• Add spironolactone 25–50 mg daily as the preferred fourth-line agent for resistant hypertension, which provides additional blood pressure reductions of approximately 20–25 mmHg systolic / 10–12 mmHg diastolic when added to triple therapy. 1, 2

• Monitor potassium closely when adding spironolactone to losartan, as hyperkalemia risk is significant with dual renin-angiotensin-aldosterone system blockade. 1

• Consider referral to a hypertension specialist if blood pressure remains ≥160/100 mmHg despite four-drug therapy at optimal doses, or if there are concerning features suggesting secondary hypertension (primary aldosteronism, renal artery stenosis, obstructive sleep apnea, pheochromocytoma). 2

Common Pitfalls to Avoid

• Do not add a beta-blocker as the third agent unless there are compelling indications (angina, post-myocardial infarction, heart failure with reduced ejection fraction, atrial fibrillation requiring rate control)—beta-blockers are less effective than diuretics for stroke prevention and cardiovascular events in uncomplicated hypertension. 2

• Do not combine losartan with an ACE inhibitor (dual renin-angiotensin system blockade), as this increases the risk of hyperkalemia, acute kidney injury, and hypotension without added cardiovascular benefit. 2

• Do not delay treatment intensification—your patient has stage 2 hypertension requiring prompt action within 2–4 weeks to reduce cardiovascular risk. 1, 2

• Do not assume treatment failure without first confirming adherence, excluding white coat hypertension, and ruling out secondary causes or interfering substances. 2

Standard Metabolic Tests to Order

• Basic metabolic panel (sodium, potassium, creatinine, glucose)
• Lipid panel
• Urinalysis
• Electrocardiogram
• Consider hemoglobin A1c if diabetes risk factors present

These tests help identify target organ damage, secondary causes of hypertension, and cardiovascular risk factors that may influence treatment decisions. 1