What additional therapy can be added to ramipril (Angiotensin-Converting Enzyme Inhibitor) 10 mg once daily and chlorthalidone (Thiazide-like Diuretic) 25 mg once daily for a 60-year-old male with uncontrolled Hypertension?

From the Guidelines

For a 60-year-old male with uncontrolled hypertension despite treatment with ramipril 10 mg daily and chlorthalidone 25 mg daily, adding a calcium channel blocker (CCB) such as amlodipine 5-10 mg once daily would be an appropriate next step. This recommendation is based on the most recent guidelines for the management of elevated blood pressure and hypertension, which suggest that combining drugs from different classes can have additive or synergistic effects and lead to greater blood pressure reduction than increasing the dose of one drug 1. The 2024 ESC guidelines recommend the use of single-pill combinations containing two of the major drug classes, including ACE inhibitors, ARBs, dihydropyridine CCBs, and thiazide or thiazide-like diuretics, as first-line BP-lowering medications, either alone or in combination.

Some key points to consider when adding a CCB to the patient's treatment regimen include:

• Starting at a low dose, such as 5 mg daily, and titrating to 10 mg if needed after 2-4 weeks
• Monitoring blood pressure regularly after adding this medication
• Assessing the patient for potential side effects, such as peripheral edema
• Considering alternatives, such as a beta-blocker (e.g., metoprolol) or a mineralocorticoid receptor antagonist (e.g., spironolactone 25 mg daily), if amlodipine is not tolerated or contraindicated

The choice of a CCB, such as amlodipine, is supported by studies that demonstrate its efficacy in reducing blood pressure and improving cardiovascular outcomes 1. Additionally, the use of a CCB in combination with an ACE inhibitor and a thiazide-like diuretic is consistent with the principle of combining medications from different classes with complementary mechanisms of action.

It's worth noting that, if the patient's blood pressure remains uncontrolled after the addition of a CCB, other treatment options, such as the addition of a mineralocorticoid receptor antagonist (e.g., spironolactone) or a beta-blocker, may be considered, as recommended by the 2018 American Heart Association scientific statement on resistant hypertension 1. However, based on the most recent and highest quality evidence, adding a CCB, such as amlodipine, to the patient's treatment regimen is the most appropriate next step.

From the Research

Additional Therapy for Uncontrolled Hypertension

To manage uncontrolled hypertension in a 60-year-old male patient already taking ramipril (Angiotensin-Converting Enzyme Inhibitor) 10 mg once daily and chlorthalidone (Thiazide-like Diuretic) 25 mg once daily, several options can be considered based on existing evidence:

• Adding a calcium channel blocker, as suggested by the study 2, which found that a fixed-dose triple combination of antihypertensive drugs, including a calcium channel blocker, improved blood pressure control in patients with uncontrolled hypertension.
• Considering a fixed-dose combination that includes amlodipine, losartan, and chlorthalidone, as studied in 3, which showed that the pharmacokinetic profiles of this combination were equivalent to those of the separate components, indicating potential efficacy and tolerability.
• The use of ramipril in combination with other antihypertensive agents, such as felodipine, as discussed in 4, which indicates that such combinations can be effective in managing essential hypertension, especially in cases where monotherapy is insufficient.

Potential Therapeutic Options

Based on the provided studies:

• Amlodipine, a calcium channel blocker, could be added to the current regimen, given its efficacy in combination with ACE inhibitors and diuretics, as indicated by 2 and 3.
• Felodipine, another calcium channel blocker, in combination with ramipril, as mentioned in 4, could also be considered for its effectiveness in controlling hypertension.
• The choice of additional therapy should be guided by the patient's specific clinical profile, including any comorbid conditions, potential drug interactions, and side effect profiles, as discussed in 5 and 6.

Considerations for Therapy Adjustment

When adjusting the therapeutic regimen for a patient with uncontrolled hypertension:

• It is crucial to monitor blood pressure regularly and adjust the medication regimen as needed to achieve target blood pressure values, as emphasized in 2.
• The patient's response to the current medication, including any side effects or tolerability issues, should be carefully evaluated before adding new medications, as noted in 5 and 6.
• The potential benefits of fixed-dose combinations, including improved adherence and simplified treatment regimens, should be considered, as discussed in 3 and 4.