Add a Calcium Channel Blocker (Amlodipine) to Losartan
For this patient with uncontrolled hypertension on losartan 100mg who cannot tolerate chlorthalidone, add amlodipine 5-10mg daily as the second-line agent. This creates the evidence-based combination of an ARB plus a calcium channel blocker, which is highly effective and avoids the diuretic class that caused his chest pain 1, 2.
Rationale for Calcium Channel Blocker Addition
The 2024 ESC guidelines explicitly recommend adding a calcium channel blocker to an ARB when a patient cannot tolerate or has contraindications to thiazide diuretics 1.
The combination of ARB plus calcium channel blocker provides complementary mechanisms—vasodilation through calcium channel blockade and renin-angiotensin system inhibition—resulting in additive blood pressure reduction 1, 2.
This dual therapy is particularly effective, with studies showing superior BP control compared to either agent alone, and is appropriate before moving to triple therapy 3.
Specific Dosing Recommendation
Start amlodipine 5mg once daily, which can be increased to 10mg daily if BP remains uncontrolled after 2-4 weeks 4, 5.
Amlodipine can be taken with or without food, ideally at the same time each day for consistency 4.
The losartan should remain at 100mg daily, as this is the maximum recommended dose for hypertension 5.
Target Blood Pressure and Monitoring
Target BP is <140/90 mmHg minimum, ideally <130/80 mmHg if well tolerated 1.
Reassess BP within 2-4 weeks after starting amlodipine, with the goal of achieving target within 3 months 1, 2.
Monitor for peripheral edema, the most common side effect of amlodipine, though this may be attenuated by the concurrent ARB use 2, 4.
If Blood Pressure Remains Uncontrolled
If BP remains elevated after optimizing to losartan 100mg plus amlodipine 10mg, add a thiazide-like diuretic as the third agent 1, 2.
However, given his prior chest pain with chlorthalidone, carefully explore whether this was truly drug-related or coincidental before reintroducing any diuretic 1.
If diuretics remain contraindicated or not tolerated, spironolactone 12.5-25mg daily is the preferred alternative fourth-line agent for resistant hypertension 1.
Important Clinical Considerations
Do not combine losartan with an ACE inhibitor, as dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional benefit 1, 2.
Confirm medication adherence and consider home BP monitoring to rule out white coat hypertension before further escalation 2.
Reinforce lifestyle modifications including sodium restriction to <2g/day, weight management, regular exercise, and alcohol limitation, which can provide additive BP reductions of 10-20 mmHg 1.
Check renal function and serum potassium 2-4 weeks after starting amlodipine, particularly given the ARB use 2.
Alternative Consideration for Black Patients
If this patient is Black, the combination of amlodipine plus a thiazide diuretic may be more effective than amlodipine plus losartan, though the ARB is still beneficial 1, 2.
For Black patients specifically, consider whether switching from losartan to a different regimen (CCB plus thiazide) might be more effective, though this requires careful discussion about the prior chest pain episode 1.