Resistant hypertension (ReHy) is an emerging clinical and public health problem which tends
to increase because populations are living longer and there is a growing global epidemic of
obesity, diabetes and sleep apnea. It is also tempting to speculate that the excessive
dietary salt ingestion reported in many countries can contribute substantially to the risk of
ReHy development. ReHy is defined as persistent high blood pressure (above the target goal)
in spite of the use of at least 3 antihypertensive agents of different classes, one of them
must being diuretics.
Data regarding the exact prevalence of ReHy are very limited. In addition, little data is
available about 3-drug combinations but a simplified treatment algorithm has demonstrated
that a combination of a diuretic plus an angiotensin-converting enzyme inhibitors (ACEi) or
an angiotensin-receptor blocker (ARB) plus diuretic, adding a calcium channel blocker when
necessary, controlled 64% of hypertensive patients and, in addition, was even more efficient
than the current guideline-based management. By contrast, the fourth drug to be added-on the
triple regimen is still controversial and guided by empirical choices or personal
preferences. Recent studies suggest the emerging role of spironolactone as the "first-line"
fourth drug for treating resistant hypertension. Conversely, because of the
pathophysiological rationale, others have proposed the use of β-blockers or even centrally
acting agents for managing the sympathetic hyperactivity. The present concerns about the
limited blood pressure reducing effect of β-blockers, especially in elderly people, the
potent effect of centrally acting agents and our personal experience are pointing to
clonidine as the fourth drug to be added-on to a multidrug combination for reaching optimal
blood pressure in patients with ReHy. Nevertheless, no studies have been performed comparing,
head-to-head, which one is the best fourth drug (spironolactone or clonidine) to be added-on
to a common used multidrug combination in order to treat this condition.
Therefore, the principal objectives of the ReHOT Trial are to assess prospectively: (1) the
prevalence of ReHy in a cohort of outpatients with stage II hypertension; (2) the effect of
spironolactone on blood pressure, in comparison to clonidine, when added to a multidrug
combination consisting of chlorthalidone plus ACEi (or ARB) plus amlodipine, all of 3
up-titrated to the highest dose; (3) the role of measuring sympathetic nervous system
activity and renin-angiotensin-aldosterone activity on predicting the response of blood
pressure to spironolactone and clonidine.
Phase:
Phase 4
Details
Lead Sponsor:
Instituto do Coracao
Collaborator:
Conselho Nacional de Desenvolvimento Científico e Tecnológico