What is the most appropriate additional treatment for a 52-year-old woman with hypertension, currently on Losartan (angiotensin II receptor antagonist) and Chlorthalidone (thiazide-like diuretic), with a blood pressure of 145/82 mmHg, normokalemia (serum potassium level of 3.6 mEq/L), and normal renal function (serum creatinine level of 0.8 mg/dL)?

From the Guidelines

The most appropriate additional treatment for this patient is amlodipine (option B). This 52-year-old woman with hypertension is currently on losartan (an angiotensin receptor blocker) and chlorthalidone (a thiazide-like diuretic), but her blood pressure remains elevated at 145/82 mm Hg despite medication adherence and dietary sodium restriction. According to the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1, combination BP-lowering treatment is recommended for most patients with confirmed hypertension as initial therapy, with preferred combinations including a RAS blocker with a dihydropyridine CCB or diuretic. Adding amlodipine, a calcium channel blocker, would provide complementary antihypertensive action through a different mechanism, as it works by relaxing vascular smooth muscle, leading to vasodilation and reduced peripheral resistance. This triple combination therapy (ARB, thiazide-like diuretic, and calcium channel blocker) represents a rational approach for resistant hypertension, as recommended by the guidelines 1. Amlodipine would not worsen the patient's borderline low potassium level of 3.6 mEq/L, which is likely due to the chlorthalidone. Some key points to consider in this decision include:

• The patient's blood pressure is not controlled with the current two-drug combination, making a third agent necessary.
• The guidelines recommend a RAS blocker with a dihydropyridine CCB or diuretic as a preferred combination 1.
• Amlodipine is a suitable choice because it does not have overlapping mechanisms with losartan and is not likely to worsen hypokalemia.
• Other options like aliskiren (a direct renin inhibitor) are not recommended in combination with ARBs, and hydralazine is typically reserved for more severe or resistant hypertension and has more side effects than amlodipine. The guidelines also mention that if BP is not controlled with a two-drug combination, increasing to a three-drug combination is recommended, usually a RAS blocker with a dihydropyridine CCB and a thiazide/thiazide-like diuretic, and preferably in a single-pill combination 1. Therefore, adding amlodipine to the patient's current regimen is the most appropriate next step in managing her hypertension.

From the FDA Drug Label

If goal blood pressure (<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of losartan or atenolol was then increased to 100 mg once daily. The most appropriate additional treatment for this patient is Hydrochlorothiazide.

• The patient's current blood pressure is 145/82 mmHg, which is above the goal blood pressure of <140/90 mmHg.
• According to the drug label, if the goal blood pressure is not reached, hydrochlorothiazide (12.5 mg) should be added first.
• This approach is consistent with the treatment strategy used in the LIFE study, where hydrochlorothiazide was added to losartan or atenolol if goal blood pressure was not achieved 2.

From the Research

Additional Treatment Options

The patient is currently taking losartan and chlorthalidone for hypertension, but her blood pressure is still elevated at 145/82 mm Hg. Considering the provided evidence, the following options can be evaluated:

• Amlodipine is a calcium channel blocker that has been shown to be effective in reducing blood pressure and is well-tolerated as monotherapy or in combination with other antihypertensive drugs 3, 4, 5, 6.
• The patient is already taking losartan, an angiotensin II receptor blocker, and chlorthalidone, a diuretic. Adding amlodipine to this regimen could provide additional blood pressure reduction, as combination therapies with amlodipine and other agents have been shown to be effective in reducing cardiovascular risk 5, 6.
• A fixed-dose combination of amlodipine, losartan, and chlorthalidone has been studied, and its pharmacokinetic profile is equivalent to that of the separate components 7.

Recommended Course of Action

Based on the evidence, adding amlodipine to the patient's current regimen of losartan and chlorthalidone may be a suitable option to further reduce her blood pressure. This decision is supported by studies demonstrating the efficacy and safety of amlodipine in combination with other antihypertensive agents 3, 4, 5, 6.

Key Points to Consider

• Amlodipine has a long half-life and duration of action, allowing for sustained blood pressure control 6.
• Combination therapies with amlodipine have been shown to reduce cardiovascular risk and are well-tolerated 5, 6.
• The pharmacokinetic profile of a fixed-dose combination of amlodipine, losartan, and chlorthalidone is equivalent to that of the separate components 7.

The most appropriate additional treatment option is: B Amlodipine