Hospital del Mar Research Institute Hospital del Mar Research Institute

Kidney Disease Marta Crespo and Clara Barrios


Resistant Hypertension

Arterial hypertension is the leading cause of morbidity and mortality due to cardiovascular diseases, making it the pathology responsible for a greater number of deaths worldwide. Thus, HT increases the likelihood of development of all clinical forms of cardiovascular disease, including ischemic heart disease, stroke, peripheral vascular disease and heart failure. In the last few years numerous controlled clinical trials have shown that it is possible to reduce the incidence of cardiovascular complications by reducing blood pressure (BP) through antihypertensive treatment, basically pharmacological.

However, the translation into usual clinical practice is suboptimal, so that the degree of BP control in the different epidemiological studies is usually no higher than 30-40% of patients, although it seems recently to have reached rates of control of around 50% in some country. The causes of non-control can be multiple, including among others the lack of compliance or the existence of a cause of undetected secondary hypertension, but beyond these factors there is an important percentage of subjects who maintain BP above normal despite adequate pharmacological treatment. In this line, resistant arterial hypertension (RH) is defined as an office systolic and diastolic BP higher than 140 mmHg and 90 mmHg, respectively, despite treatment with ≥ 3 drugs in adequate doses, one of them a diuretic, or hypertension requiring treatment with 4 or more antihypertensive drugs regardless of clinical BP values.

The prevalence of RH mostly depends on the context in which it is evaluated; thus, recent data show a prevalence of ≈ 15% in our country at the level of primary care, whereas it rises to ≈ 20% if it is determined in specialized units or in clinical trials.

Resistant hypertension is characterized by a worse prognosis, since the subjects who suffer it develop a higher degree of atherosclerosis and vascular damage, resulting in a higher prevalence of organic damage and a higher incidence of cardiovascular events. On the other hand, a non-negligible percentage of patients supposedly with treatment-RH have shown to have indeed pseudo-resistance or false RH when 24-hour ambulatory blood pressure monitoring (ABPM-24h) was performed. Thus, in Spain, a large cohort of more than 8000 patients with RH showed normal 24h-BP (130/80 mmHg) in 37.5% of subjects. The value of ABPM in these subjects is not only diagnosis, but also prognosis. The achievement of an ABPM-24h is therefore fundamental, to clearly identify patients with true RH compared to those with pseudo-resistant hypertension.

In this context, our group recently conducted a randomized controlled trial, the DENERVHTA Study, to evaluate the efficacy of radiofrequency renal sympathetic denervation in patients with RH, as compared with the addition of spironolactone, a drug that blocks the mineralocorticoid receptors, to the therapeutic regimen at baseline. We showed that spironolactone is more effective than renal denervation to reduce 24h –systolic and –diastolic BP when added to optimized pharmacological treatment in patients with RH.

Going in depth with RH subjects, we are now engaged in a new research project, the ATHAN study, in order to assess whether the implementation of a specific strategy to improve adherence for 3 months results in reduced peripheral 24h-systolic blood pressure (SBP) in patients with RH or uncontrolled hypertension with 2 antihypertensive drugs. The design is that of an interventional, prospective, randomized, controlled, parallel groups, open study of a cohort of 150 consecutively recruited patients with RH or patients with uncontrolled hypertension with 2 antihypertensive drugs, confirmed by 24h-ABPM.

These patients will be randomized (1: 1) to receive a specific program to improve adherence (intervention group) or routine follow-up (control group), with office BP measurement and determination of antihypertensive drugs in urine at pre-randomization, 3, 6 and 12 months; peripheral and central 24h-ambulatory BP monitoring will be performed at pre-randomization, at 3 and 12 months.

We want to ascertain by one hand the reliability of the determination of antihypertensive drugs and/or its metabolites in urine to detect non-adherent to treatment patients, and on the other hand to show whether a specific support program to improve treatment adherence could lead to a better BP control and a lower cardiovascular risk in these patients.

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