286
Definition of RH
Resistant hypertension is defined as uncontrolled hypertension (i.e., office BP
≥140/90 mmHg in a patient <80 years or systolic blood pressure [BP] ≥150 mmHg
in a patient ≥80 years, confirmed by home self-measurement or ambulatory moni-
toring of BP), despite antihypertensive treatment consisting of appropriate lifestyle
changes and triple drug therapy for at least 4 weeks, in optimal doses, including a
diuretic [ 11 ]. However, before making the diagnosis of RH, adherence to prescribed
therapy should be confirmed (e.g., by using specific questionnaires or serum drug-
level measurements), and possible interference of pro-hypertensive factors, such as
high salt intake, excess alcohol consumption, or use of vasopressor drugs (like
cyclosporine, steroids, erythropoietin, or oral contraceptives), should be searched
for [ 11 ]. If true RH is established, causes of secondary hypertension including pri-
mary aldosteronism, pheochromocytoma, hypercorticism, renal artery stenosis, or
sleep apnea syndrome should also be considered and investigated [ 11 ].
Treatment of RH
In patients with RH for which no curable cause can be identified, the addition of a
fourth antihypertensive agent is indicated. This should preferably be an MR antago-
nist (spironolactone or eplerenone), in the absence of contraindications [ 11 ].
MR antagonists are weak diuretics, but they play a special role in the manage-
ment of RH, for several reasons. Patients with RH often have secondary hyperal-
dosteronism and may also exhibit the so-called aldosterone escape or
breakthrough. This phenomenon is defined as an increase in aldosterone levels
after initiation of ACEIs or ARBs, most likely by non-ACE pathways of angio-
tensin II activation [ 12 ]. However, MR antagonists were shown to improve BP
control in patients with RH, regardless of circulating aldosterone levels [ 13 ]. The
RCT Addition of Spironolactone in Patients with Resistant Arterial Hypertension
(ASPIRANT) [ 14 ] evaluated the antihypertensive effects of spironolactone
25 mg/day in 117 patients with RH after treatment for 8 weeks. Existing antihy-
pertensive treatment was continued during this period. The study showed that
systolic BP was reduced significantly in treated patients, with no adverse effects.
More recently, the Prevention and Treatment of resistant Hypertension With
Algorithm-Guided Therapy (PATHWAY-2) study [ 15 ] demonstrated the superior
BP-lowering effect (and similarly good tolerance) of spironolactone 25–50 mg/
day, as compared to each of bisoprolol, doxazosin, and placebo, in patients with
RH already on ACD regimen.
In cases with contraindications, resistance, or intolerance to spironolactone, the
use of a BB, an alpha-blocker, or a centrally acting agent is recommended [ 11 ].
L. Segall