Clinical Perspective

Resistant or difficult-to-treat hypertension is a common clinical problem affecting 10 to 15% of treated hypertensive patients. Effective management of resistant hypertension firstly requires distinguishing pseudo-resistant from true resistant hypertension. Common causes of pseudo-resistance include inaccurate blood pressure (BP) measurement, white coat effect, poor medication adherence, and undertreatment. Pharmacologic treatment of resistant hypertension requires use of effective multidrug antihypertensive regimens, including especially diuretic therapy. An initial three-drug regimen of an angiotensinconverting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), amlodipine, and a long-acting thiazide diuretic is recommended. Chlorthalidone is recommended as the preferred thiazide diuretic of choice given its long half-life and superior efficacy. A large body of literature now clearly establishes spironolactone as the most effective fourth medication for treatment of resistant hypertension. Renal nerve denervation (RND) is under intensive investigation to determine its true antihypertensive benefit, especially for treating uncontrolled resistant hypertension. Recent studies suggest that while the technique will likely provide some benefit in terms of additional BP reduction, it will not likely cure patients of their resistant hypertension as most subjects participating in studies of RND have generally continued medical therapy with use of the same or nearly the same number of medications. Accordingly, clinicians, even with the availability of renal nerve derivation, will have to remain facile in prescribing multiple drug combinations for treating resistant hypertension.