This protocol addresses the clinical situation in which blood pressure remains uncontrolled despite three antihypertensive medications — including a diuretic at maximally tolerated doses — or is controlled only when four or more medications are required.
Resistant hypertension is defined as BP above goal despite treatment with three antihypertensive medications with complementary mechanisms of action, including a diuretic at maximally tolerated doses, or BP at goal but requiring four or more medications.
The prior step involved the addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone) as a fourth agent. When that approach has not achieved a blood pressure goal of <130/80 mm Hg — or when MRA therapy is not tolerated or is contraindicated — this protocol describes the next step.
In this setting, the addition of an agent from a distinct pharmacological class is the recommended strategy. The full structured protocol identifies specific classes of agents appropriate for this step; only a partial overview is provided here.
Target: BP <130/80 mm HgResistant hypertension is defined as BP above goal despite treatment with 3 antihypertensive medications with complementary mechanisms of action, including a diuretic at maximally tolerated doses or BP at goal but requiring ≥4 medications (Figure 8).
In adults with uncontrolled resistant hypertension who cannot tolerate or have contraindications to MRA, the addition of one of the following agents or classes—amiloride, BBs, alpha-blockers, central sympatholytic drugs, dual endothelin receptor antagonists, or direct vasodilators—is reasonable to control BP.
When spironolactone or eplerenone are not tolerated due to side effects or cost, amiloride (10-20 mg) has been shown to be as effective as spironolactone in adults with resistant hypertension.
Direct vasodilators such as hydralazine and minoxidil should be used in combination with a BB and a loop diuretic given their effects on sympathetic tone, sodium reabsorption, and fluid retention.
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