Resistant Hypertension On Treatment - Sequential Nephron Blockade Compared to Dual Blockade of the Renin-angiotensin-aldosterone System Plus Bisoprolol in the Treatment of Resistant Arterial Hypertension: A Randomized Trial (ResHypOT)

Introduction

Resistant hypertension (RH) is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions, at their maximum recommended tolerated doses for at least six months; one preferably should be a diuretic. True RH should be differentiated from pseudo resistance, which occurs due to non-adherence to treatment, inadequate BP measurements, inadequate doses of medications, inappropriate therapeutic regimens, or the presence of the so-called white-coat effect.

The exact prevalence of RH is unknown. In controlled randomized studies with thousands of hypertensive patients, approximately 25% to 30% of participants did not achieve the BP goal recommended by guidelines despite receiving three or more antihypertensive drugs; these studies included careful assessments of adherence to therapy and even ambulatory BP monitoring (ABPM), which excludes patients with pseudo resistance.

Observational data from the North American National Health and Nutrition Examination Survey (NHANES) collected in 2003-2008 showed that the prevalence of RH among adults diagnosed with hypertension (HTN) in this period was 8.9% and among adults on antihypertensive treatment, it was 12.8%. Similarly, a large population study in Spain (68,000 patients) found that the prevalence of RH was 14.8% among those treated for HTN. Based on these recent studies, it is justifiable to say that the prevalence of RH is about 14%. RH is a difficult-to-manage clinical condition due to failure of patients to adhere to treatment, the physician's difficulty to adjust the medication because of genetic factors that hinder the effectiveness of treatment and medical inertia.

Pathophysiology of resistant hypertension: The mechanisms involved in the pathophysiology of RH are the vascular smooth muscle tone and increased blood volume, intensification of the activity of the sympathetic system and hyperactivity of the renin-angiotensin-aldosterone system (RAAS). Increased sensitivity to sodium appears to be the main factor in understanding the pathophysiology of this syndrome, not only as it incorporates the above mechanisms, but also as it explains, in part, the variability of therapeutic response of patients with RH. The RAAS is vital to the regulatory system that controls total body sodium as are atrial natriuretic peptide factors and pressure receptors in the atria and kidney. Sodium and water retention can lead to resistance against antihypertensive drugs. Under the physiological point of view, BP is maintained by continuous regulation of cardiac output and peripheral vascular resistance exerted at three anatomic sites: arterioles, postcapillary venules (capacitance vessels) and the heart. A fourth anatomical site of control, the kidney, contributes to the maintenance of BP by regulating intravascular volume.