Die therapeutischen Möglichkeiten bei Patienten mit
Lungenhochdruck haben sich in den letzten Jahren deutlich verbessert.
Jedoch muss bei jedem Patienten vor Einleitung einer Therapie eine ätiologische
Zuordnung erfolgen. Die pulmonale arterielle Hypertonie (PAH; Gruppe
1 der Venedig-Klassifikation) ist von anderen Formen der pulmonalen
Hypertonie (PH; Gruppen 2 – 5 der Venedig-Klassifikation)
klar abzugrenzen. Zur Behandlung der PAH stehen mit Prostazyklin-Analoga
(Prostanoide), Endothelin-Rezeptor-Antagonisten (ERA) und Phosphodiesterase-5-Inhibitoren
mittlerweile Pharmaka aus drei verschiedenen Substanzklassen zur
Verfügung, für die jeweils ein Wirksamkeitsnachweis
erbracht wurde. Eine aktuelle Metaanalyse zeigt, dass durch diese
Therapien erstaunlicherweise bereits innerhalb kurzer Beobachtungszeiträume eine
Verbesserung der Überlebensrate erzielt werden kann. Dennoch
weisen viele Patienten weiterhin eine erhebliche klinische Symptomatik
und eine deutlich eingeschränkte Lebenserwartung auf. Im
Folgenden soll ein Überblick über die aktuellen
Entwicklungen bei zugelassenen Therapien der PAH, bei der Etablierung
neuer Therapiekonzepte zur Behandlung der PAH, sowie zu den Therapiemöglichkeiten
bei anderen Formen der PH gegeben werden.
Summary
During the last years, therapeutic options for the treatment
of pulmonary arterial hypertension (PAH) have significantly improved.
However, the therapeutic concept depends on the etiology of the
disease, so that an exact classification is mandatory. Currently,
three substance classes are approved for the treatment of PAH (Group
I of the Venice Classification): Endothelin receptor antagonists,
phosphodiesterase type-5 inhibitors, and prostanoids. After the
World Conference in Dana Point (2008), recent changes in therapeutic
strategies comprise the early treatment of the disease, as well
as the increased importance of an early use of combination therapy
if treatment goals are not met. Several new substances are currently
evaluated in clinical trials. The soluble guanylate cyclase (sGC)
stimulators achieve potent, NO-independent vasodilation. Another
promising pathophysiological approach is currently evaluated by
the use of tyrosine kinase inhibitors – anti-proliferative
drugs which inhibit or even may reverse the pulmonary vascular remodeling
process. Serotonin receptor antagonists are also reported to have
anti-proliferative, anti-thrombotic and anti-fibrotic effects. Other
forms of pulmonary hypertension (Groups II-V) are strictly separated
from PAH. Evidence on treatment with PAH specific agents is strongly
needed for these groups. Patients with non-PAH pulmonary hypertension
should be referred to PAH expert centers, and preferably treated
in controlled studies.
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