Abstract
Resistant hypertension (RH) is characterized by persistently elevated blood pressure despite the use of at least three antihypertensive drug classes, including a diuretic, in adequate doses. This condition presents a clinical challenge due to the significantly increased cardiovascular risk and associated morbidity and mortality. In recent years, RH management has evolved considerably, driven by advancements in pharmacological interventions, non-pharmacological techniques and patient stratification based on genetic factors and biomarkers. Effective treatment requires a multidisciplinary approach, ranging from lifestyle modifications and medication adherence monitoring to the utilization of technologies such as renal sympathetic denervation and baroreflex devices.
Keywords: Resistant hypertension; Blood pressure control; Renal denervation; Baroreflex; Pharmacological management
Introduction
Hypertension is a leading cause of morbidity and mortality worldwide,
responsible for complications such as stroke, heart failure and chronic kidney
disease1,2. Within this spectrum,
resistant hypertension (RH) represents a particularly challenging subgroup. RH
is defined as persistently elevated blood pressure despite concurrent use of
three or more antihypertensive medications from different classes, including a
diuretic3-5. The estimated prevalence of
RH varies between 10% and 20% among hypertensive patients, depending on the
population studied and diagnostic criteria applied6,7. This condition is associated with a
significantly elevated cardiovascular risk, demanding special attention from
healthcare providers. However, RH diagnosis is not always straightforward, as
factors such as poor adherence to treatment, inaccurate blood pressure
measurements and white-coat hypertension can simulate RH, characterizing
so-called "pseudo-resistant hypertension8-10. “Pathophysiological mechanisms underlying
RH include heightened sympathetic nervous system activation, renal sodium
retention, endothelial dysfunction and insulin resistance11,12. These
factors contribute to blood pressure control difficulties, necessitating more
complex and individualized therapeutic approaches. Historically, RH management
relied on adjustments in pharmacological regimens and lifestyle interventions,
such as dietary sodium reduction and weight loss13. However, these methods frequently fail in
patients with true RH, prompting research into more effective alternatives.
Significant advancements have been made in recent years, including the
development of new drug classes and the introduction of interventional
techniques such as renal denervation. Moreover, the growing integration of
precision medicine and technological applications in hypertension management
offers promising future perspectives.
Objectives
This article aims to review recent significant advances in managing
resistant hypertension, discussing clinical applicability, knowledge gaps and
future perspectives for treating this complex condition.
Materials and Methods
A bibliographic review of articles published in PubMed, ScienceDirect
and SciELO databases was conducted to support this study.
Discussion
The management of
resistant hypertension has benefited from innovations combining advanced
pharmacological therapies, non-pharmacological interventions and emerging
technologies. Lifestyle management remains foundational in RH treatment. Sodium
reduction, weight loss, regular physical activity and alcohol consumption
reduction are associated with significant benefits. However, isolated
effectiveness is limited in patients with true RH, underscoring the necessity
of complementary strategies14.
New medications
have broadened therapeutic options for RH. Mineralocorticoid receptor
antagonists, such as spironolactone and eplerenone, have demonstrated clinical
efficacy, especially in patients with hyperaldosteronism15. Angiotensin receptor-neprilysin inhibitors (ARNIs),
like sacubitril/valsartan, have shown potential for improving blood pressure
control in specific subgroups. A crucial aspect of RH management is treatment
adherence. Studies indicate that up to 50% of patients diagnosed with RH
exhibit poor medication adherence. Utilizing technological devices, such as
blood pressure monitors connected to digital health applications and platforms,
facilitates continuous monitoring and personalized treatment.
Conclusion
Recent advances in
managing resistant hypertension offer promising perspectives for improving
blood pressure control in affected patients. Introducing new pharmacological
classes and developing interventional approaches, such as renal denervation,
represent significant steps forward. Clearly, no single solution exists for RH.
Effective management requires a multidisciplinary approach considering
pathophysiological aspects, treatment adherence and patient social conditions.
Precision medicine emerges as a powerful tool capable of personalizing
interventions and optimizing therapeutic outcomes. However, its widespread use
still faces challenges, including the need for further research and practical
implementation in clinical routines. Future advancements in artificial
intelligence and accessible technologies are expected to expand access to
therapeutic innovations. Additionally, strengthening public health policies and
educational programs will be essential to improve treatment adherence and
reduce the societal burden of resistant hypertension.
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