• Ешқандай Нәтиже Табылған Жоқ

TREATMENT OF RESISTANT ARTERIAL HYPERTENSION

In document Science & Health Care (бет 39-42)

УДК 616.12-008.331.1-08 A.K. Zhanatbekova

Semey State Medical University, Kazakhstan

Department of internship by therapy

analyses of large scale trials and observational studies have provided evidence that all drug classes with mecha- nisms of action partially or totally different from those of the existing three drug regimens can lower BP in at least some resistant hypertensive individuals. A good response has been reported to the use of mineralocorticoid receptor antagonists, i.e. spironolactone, even at low doses (25–50 mg/day) or eplerenone, the alpha-1-blocker doxazosin and a further increase in diuretic dose, loop diuretic replacing thiazides or chlorthalidone if renal function is impaired [3].

It is known the role of the RAAS in the pathogenesis of hypertension, on this basis in clinical practice known drug alisikren. Aliskiren, the first orally active direct renin inhibi- tor, was approved by the US Food and Drug Administra- tion in March 2007. It has demonstrated effective blood pressure (BP) control and is generally well tolerated as monotherapy or in combination with other antihypertensive drugs [13]. Extra advantages can be reached when it is used in combination therapy. The data from 7 randomized clinical trials for a total of 6074 participants in meta- analysis report that the aliskiren/amlodipine combination therapy had a stronger effect in lowering blood pressure as compared with the monotherapy using aliskiren [14].

In March 2012 was published results of investigation about the combination of aliskiren, amlodipine and hydro- chlorothiazide is a rational choice for combination therapy and recent studies suggest that it is safe and effective in lowering blood pressure in patients who fail dual combina- tion therapy [15].

But the ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardio-renal Disease Endpoints) trial was stopped on the recommendation of its Data Monitoring Committee (DMC) due to increased adverse events, including nonfa- tal stroke, renal dysfunction, hyperkalemia and hypoten- sion, with no apparent benefit. The major concern was increased stroke with aliskiren in comparison to placebo (2.6% versus 2%, unadjusted p = 0.04) [16]. This trial studied the effects of aliskiren in addition to ACEI or ARB therapy in patients with diabetes and renal disease (glo- merular filtration rate < 60 ml/min per 1.73 m2 or microal- buminuria). The primary endpoints of the study were time to first event for the composite endpoint of CV death, re- suscitated death, myocardial infarction, stroke, unplanned hospitalization for HF, onset of end-stage renal disease or doubling of baseline serum creatinine concentration [17].

Based on these findings, dual aliskiren and ACEI/ARB therapy is not recommended in patients with hypertension and diabetes or at least moderate renal dysfunction [13].

Nonpharmacological methods of therapy of re- sistant hypertension

The role of the sympathetic nervous system in modu- lating blood pressure has been extensively investigated during the last century, and some drugs have already been proven to efficiently act on adrenergic apparatus such as α-metildopa in the 1950 s, β-blockers in the 1960 s, α-blockers in the 1970 s, angiotensin-converting en- zyme inhibitors in the 1980 s, and moxonidine in the 1990 s. None of them, however, has turned out to be as effec- tive as renal denervation. The proof of concept for apply- ing such a therapeutic strategy mainly derives from the assumption that sympathetic nerves enter the kidneys in the walls of the renal arteries, thus affecting renal function in 3 different ways: (1) increasing the renin secretion rate through the β1-adrenergic receptors; (2) enhancing sodi- um and water reabsorption through α2B-adrenergic recep- tors; and (3) inducing renal vasoconstriction with renal blood flow and glomerular flow rate reductions through α1A-adrenergic receptors.

Therapeutic renal denervation has been explored in preclinical models and in humans since the 1950 s, when surgical renal denervation was shown to be a highly effec- tive treatment for resistant hypertension in the clinical setting. Unfortunately, the procedure was abandoned be- cause of intolerable side-effects, but gave rise to other promising surgical techniques, such as carotid barorecep- tor surgery for resistant hypertension, which showed en- couraging results.

Recently, percutaneous renal denervation has emerged as a potential mini-invasive strategy to treat re- sistant hypertension. It is a localized procedure, minimally invasive, and has no systemic side-effects. Moreover, procedure and recovery times are very short compared to the surgical procedure.

The main studies of renal denervation are the Sym- plicity HTN-1 and the randomized controlled Symplicity HTN-2 trial. In both trials, this approach was shown to successfully reduce blood pressure, without serious ad- verse events in patients with resistant hypertension [18].

Another target for the interventional treatment of re- sistant hypertension is carotid baroreceptors. Barore- ceptors are stretch-sensitive fibers located primarily in the aortic arch and each of the carotid sinuses near the area where the common carotid artery bifurcates [19]. The Rheos device (CVRx, Maple Grove, Minn) stimulates the carotid baroreceptors for better blood pressure control by taking advantage of chronic electrical activation of the afferent limb of the carotid baroreflex. The device consists of a pulse generator and bilateral perivascular carotid sinus leads that are implanted under narcotic anesthesia.

According to the findings from the Device-Based Therapy of Hypertension (DEBuT-HT) study that were recently presented, after four years of treatment, Rheos reduced systolic blood pressure by an average of 53mmHg (193mmHg versus 140mmHg). Blood pressure was re- duced significantly each year, with the largest decrease occurring in year four. Many of these patients were able to reach their blood pressure goal and reduce the number of medications that patients were taking to treat their hyper- tension from an average of 5 at baseline to 3.4 medica- tions at 4 years. Baroreflex activation therapy also im- proved functional capacity and reduced left ventricular mass without any evidence of carotid injury or stenosis [12].

Conclusion

Resistant hypertension is an increasingly common medical problem and patients with this condition are at a high risk of cardiovascular events. Because secondary hypertension may be the underlying cause of resistant hypertension, and sometimes a specific and definite treatment is available, a thorough investigation is manda- tory in patients with resistant hypertension. However, in the majority of these patients, an underlying cause cannot be found. More established approaches, such as low die- tary salt and mineralocorticoid receptor blockers are indi- cated for these patients. New technologies, such as renal denervation and carotid stimulation, may be used in the management of patients with resistant hypertension.

References:

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Papadopoulos Resistant Hypertension Workup and Ap- proach to Treatment. Int J Hypertens. Volume 2011.

13. Selçuk Şen, Soner Sabırlı, Tolga Özyiğit and Yağız Üresin. Aliskiren: review of efficacy and safety data with focus on past and recent clinical trials. Thera- pAdvChrDis (2013) 4(5) 232–241.

14. Yukai Liu, Ken Chen, Xun Kou, Yu Han, Lin Zhou, Chunyu Zeng. Aliskiren and Amlodipine in the Man- agement of Essential Hypertension: Meta-Analysis of Randomized Controlled Trials. PLOS ONE July 2013 | Volume 8 | Issue 7 | e7011.

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16. McMurray J., Abraham, W., Dickstein, K., Køber, L., Massie, B. and Krum, H. (2012) Aliskiren, ALTITUDE, and the implications for ATMOSPHERE. Eur J Heart Fail 14: 341–343.

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Renal Sympathetic Denervation for Treating Resistant Hypertension Circulation Journal Vol.77, April 2013

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Резюме

ЛЕЧЕНИЕ РЕЗИСТЕНТНОЙ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ А.К. Жанатбекова

Государственный медицинский университет города Семей, Казахстан, Кафедра интернатуры по терапии

Многочисленные мета анализы показали линейную зависимость между уровнем артериального давления (АД) и риском сердечно-сосудистых осложнений. Распространенность резистентной артериальной гипертонии в общей популяции неизвестна и варьирует в диапазоне от 1,9 до 30%. Таким пациентам показаны наиболее изу- ченные и доказанные подходы, такие как низкий уровень соли в пище и применение блокаторов рецепторов ми- нералокортикоидов. Новые технологии, такие как почечная денервация и стимуляция барорецепторов сонных артерий, также могут быть использованы в лечении пациентов с резистентной АГ.

Ключевые слова: :лечение, резистентная артериальная гипертония.

Тұжырым

РЕЗИСТЕНТТІ АРТЕРИАЛДЫ ГИПЕРТОНИЯНЫ ЕМДЕУ А.К. Жанатбекова

Семей қаласының Мемлекеттік медицина университеті, Қазақстан Терапия бойынша интернатура кафедрасы

Көптеген мета талдаулар артериалды қысым (АҚ) және жүрек-тамырдың асқынуы деңгейі арасындағы сызықтық тәуелділігін көрсетті. Резистентті артериалды гипертонияның таралуының жалпы популяциясы белгісіз және 1,9 -дан 30%-ға диапазонында басым. Мұндай науқастарға көбінесе зерттелген және дәлелденген тәсілдер көрсетілген, асқа тұздың аз деңгейі және минералокортикоидты блокатор рецепторларын қолдану ұсынылады. Резистентті артериалды гипертониямен ауыратын науқастарды емдеуде ұйқы артериясындағы барорецепторларының стимуляцисын және бүйрек денервация сияқты жаңа технологияларды қолдануға болады.

Негізгі сөздер: емдеу, резистентті артериалды гипертония.

In document Science & Health Care (бет 39-42)