Hemmung des Renin–Angiotensin–Aldosteron–Systems – Wirkstoffe, Kombinationen und Wirkungsweise

Das Renin–Angiotensin–System (RAS) ist wesentlich an der Entstehung und Progression hypertensiver Endorganschäden beteiligt. Angiotensin II hat neben der direkten vasokonstriktorischen Wirkung viele pathophysiologische Effekte: Induktion von Inflammation, endotheliale Dysfunktion, Fibrose und Tissue Remodeling. Ziel der Blutdrucktherapie ist die optimale Blutdrucksenkung per se und die hypertensive Endorganprotektion (Herz, Hirn, Niere, Gefäße, Auge) zur Verbesserung der kardiovaskulären Morbidität und Mortalität. ACE–Hemmer und AT₁–Rezeptorblocker sind First–Line–Antihypertensiva und bei proteinurischen Patienten anderen Antihypertensiva hinsichtlich der Verminderung der Progression der Niereninsuffizienz überlegen (Evidenzgrad A). Die Indikation für ACE–Hemmer und AT₁–Rezeptorblocker bei Hypertonie ist die diabetische Nephropathie (kontrollierte Studien für ACE–Hemmer bei Typ 1, für AT₁–Rezeptorblocker für Typ 2). ACE–Hemmer haben bei hypertensiven Patienten kardioprotektive Effekte bei linksventrikulärer Hypertrophie, bei Herzinsuffizienz, nach Myokardinfarkt und zur Prävention von Vorhofflimmern. Die direkte Renininhibition mit Aliskiren ist vor allem für die antihypertensive Kombinationstherapie geeignet. Indikationen für eine duale Blockade des RAS können therapierefraktäre Hypertonie, Herzinsuffizienz oder eine Proteinurie (> 1 g/Tag) trotz Blutdruckkontrolle und aufdosierter ACE–Hemmung sein. Unter der Therapie mit Aldosteron–Antagonisten und ebenso bei dualer Blockade des RAS sind Kontrollen des Serumkaliums und –kreatinins erforderlich, um ernste Hyperkaliämien zu verhindern. RAS–Blocker sind in der Schwangerschaft aufgrund des Missbildungsrisikos kontraindiziert.

The renin–angiotensin–system is mainly involved in the development and progression of hypertensive end–organ damage. Beside vasoconstrictive actions, Angiotensin II has many pathophysiological effects causing inflammation, endothelial dysfunction, fibrosis and tissue remodeling. Goals of antihypertensive treatment are blood pressure lowering per se and target endorgan protection (heart, brain, kidneys, vessels, eye) to improve cardio–vascular morbidity and mortality. ACE inhibitors and AT₁ receptor blockers are first–line antihypertensive agents and superior in the delay of progression of renal disease in patients with proteinuria (evidence level A). ACE inhibitors and AT₁ receptor blocker are indicated in hypertensive patients with diabetic nephropathy (randomised controlled trials with ACE inhibitors in type 1 diabetics, with AT₁ receptor blockers in type 2). ACE inhibitors and AT₁ receptor blockers are cardioprotective in hypertensive patients with left ventricular hypertrophy, in heart failure, after myocardial infarction and can be preventive of atrial fibrillation. Direct renin inhibition with aliskiren is appropriate for the combined antihypertensive treatment. The addition of an AT₁ receptor blocker to an ACE inhibitor can be beneficial in patients with refractory hypertension, heart failure, or proteinuria > 1 g/day despite optimum blood pressure control. Under treatment with a combination of an ACE inhibitor and an AT₁ receptor blocker or the use of an aldosterone blocker tests of serum potassium and creatinine values are indicated to prevent serious hyperkalemia. Blocker of the renin–angiotensin system are contra–indicated in pregnancy because of the risk of fetal deformities.

Key words

Renin–angiotensin–aldosterone system - ACE–inhibition - AT₁ receptor blockers - aliskiren - hypertension - hypertensive endorgan damage

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