Is it acceptable to be on 5 antihypertensive medications?

From the Guidelines

Being on 5 antihypertensive medications can be acceptable in certain situations, particularly for patients with resistant hypertension who haven't achieved target blood pressure with fewer medications. This approach is supported by the most recent guidelines, including the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. According to these guidelines, combination therapy is recommended for patients with hypertension, and the use of multiple medications can be necessary to achieve target blood pressure levels.

Key Considerations

• Resistant hypertension is defined as blood pressure that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes 1.
• The 2020 International Society of Hypertension global hypertension practice guidelines recommend optimizing the current treatment regimen, including health behavior change and diuretic-based treatment, before adding additional medications 1.
• The 2024 ESC guidelines recommend upfront low-dose combination therapy, with a preference for single-pill combinations, and suggest that patients with resistant hypertension should be considered for referral to an expert center for appropriate work-up 1.

Medication Management

• The goal is to find the minimum effective combination that controls blood pressure while minimizing side effects.
• Regular monitoring of blood pressure, kidney function, and electrolytes is essential when on multiple antihypertensives.
• Patients on multiple medications should work with their healthcare provider to periodically reassess whether all medications are necessary or if the regimen can be simplified.

Lifestyle Modifications

• Lifestyle modifications, such as diet and exercise, are also important for managing hypertension and should be considered in conjunction with medication therapy.
• Patients with resistant hypertension should be encouraged to make lifestyle changes to help manage their condition, in addition to taking their medications as prescribed.

From the Research

Acceptability of Multiple Antihypertensive Medications

• The use of multiple antihypertensive medications is a common practice in the management of hypertension, particularly in cases of resistant hypertension 2, 3, 4, 5.
• Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses 2, 5.
• In some cases, four or more antihypertensive drugs may be required to achieve blood pressure control, and this is considered acceptable in the management of resistant hypertension 5.

Rationale for Multiple Medications

• The rationale for using multiple antihypertensive medications is based on their different effects on the renin-angiotensin system, which improves antihypertensive efficacy 6.
• Combining two or more different classes of antihypertensive drugs has an additive effect on lowering blood pressure, and does not increase adverse events 3, 6.
• The use of fixed-dose combinations of antihypertensive medications can improve blood pressure control and aid compliance with long-term therapy 6.

Specific Medications and Combinations

• Common antihypertensive medications used in combination therapy include thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) 3.
• Mineralocorticoid receptor antagonists, such as spironolactone, may be used as a fourth-line treatment for patients with resistant hypertension 2.
• Other medications, such as beta-blockers, clonidine, and doxazosin, may also be used in the management of resistant hypertension 2, 4.