[Sildenafil for treatment of severe pulmonary hypertension and commencing right-heart failure].
Pulmonary hypertension (PHT) is mainly explained by four underlying pathophysiological phenomena: 1. Vasoconstriction, 2. reduction of pulmonary vascular bed, 3. reduction in vessel elasticity, and 4. obliteration of the vessel lumen by thrombotic material and subsequent cellular alterations of the vessel wall (vascular remodeling). Chronic right heart load is thus a consequence of increased pulmonary pressure and vascular resistance. Main targets of advanced therapeutic strategies are therefore first: resolution of chronically increased vascular tone by smooth muscle cell relaxation (vasodilators), second: reversal of vascular remodeling and third: prevention from pulmonary embolization and/or in-situ thrombosis (chronic anticoagulation). Long term administration of high dose calcium channel blockers (though operative only in a minority of 10 - 15 % of all patients), prostanoids (eg. prostacyclin, iloprost), and the recently approved unselective oral endothelin antagonist bosentan are regarded as established medical therapies for treatment of chronic PHT. However, applicability of these substances can be limited by potentially serious adverse events and/or necessity for elaborate parenteral application. Recent data are indicative for a strong pulmonary vasodilative potency of the selective phosphodiesterase-5 (PDE5) inhibitor sildenafil. Smaller clinical studies and numerous case reports underline the good tolerability of this orally applied substance in various form of PHT. Based on these encouraging results, the simple availability, and the low costs (in comparison to "established therapies") of the drug, sildenafil is currently widely used in an "off-label" indication for treatment of PHT. Controlled randomized studies have to confirm the current findings, before general recommendations regarding the use of sildenafil for treatment of PHT can be made.
Ghofrani
H A
HA
Medizinische Klinik II, Zentrum für Innere Medizin der Justus-Liebig-Universität Giessen, Germany.
Olschewski
H
H
Seeger
W
W
Grimminger
F
F
D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008955:Models, Cardiovascular; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use*; D011650:Pulmonary Alveoli / Q000098:blood supply; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014664:Vasodilation; D014665:Vasodilator Agents / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate