«CONCLUSION: Among the therapies currently available for the treatment of PAH, the PDE-5 inhibitors are a safe, effective, and well-tolerated therapeutic option. Sildenafil and tadalafil are FDA-approved for the treatment of PAH without respect to functional class. However, there is a paucity of data regarding vardenafil in PAH, and its use cannot be currently recommended. Whether as upfront therapy or ad-on therapy, a solid body of research now supportssildenafil and tadalafil as key treatments in PAH.»
«Background: Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated lead to right-heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left-heartdisease (PH-LH); Group 3 comprises PH as a result of lungdiseases or hypoxia, or both; Group 4 includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorder. Phosphodiesterase type 5 (PDE5) inhibitors increasevasodilation and inhibit proliferation.»
«RESULTS: We included 36 studies with 2999 participants (with pulmonary hypertension from all causes) in the final review. Trials were conducted for 14 weeks on average, with some as long as 12 months. Two trials specifically included children.
CONCLUSIONS: PDE5 inhibitors appear to have clear beneficial effects in group 1 PAH. Sildenafil, tadalafil and vardenafil are all efficacious in this clinical setting, and clinicians should consider the side‐effect profile for each individual when choosing which PDE5 inhibitor to prescribe.
FINDINGS: Pulmonary hypertension (PH) (defined as a mean pulmonary artery pressure ≥ 25 mmHg at rest on right‐heart catheterisation) comprises a complex group of conditions (see Table 15), characterised by increased right ventricular afterload, which ultimately lead to right‐heart failure (McLaughlin 2009). The increased afterload may be due to passive transmission of high left‐sided pressures (post‐capillary pulmonary hypertension), obstruction of the pulmonary arterial bed (pre‐capillary pulmonary hypertension) or a combination of both. Pulmonary arterial hypertension (PAH‐WHO Group 1) is a group of diseases where pulmonary hypertension occurs in the setting of increased pulmonary vascular resistance. The more recent availability of medications and therapies targeting the pulmonary arterial bed has led to the prospect of an improvement in what had previously been a very poor prognosis. Although PAH is rare, PH secondary to left‐heartdisease and lungdisease is much more common. The availability of drugs with efficacy in PAH has led to great interest in the use of these drugs in other forms of pulmonary hypertension.»
«CONCLUSION: Although WHO Group 1 PH is rare, the majority of research has been done in this group, yielding three pharmacological classes available for its treatment: PDE5 inhibitors, prostacyclin analogs and ERAs. However, the treatments available are not ideal. The only drug class that has displayed a mortality benefit, prostacyclin analogs, has a poor side-effect profile and requires difficult to use parenteral delivery methods. New treatments (including an oral prostacyclin analog) are under investigation and range from repurposed drugs that are used to treat other diseases, to treatments targeting novel pathways, to gene therapy.»
«RESULTS: Four studies recruiting 77 participants met the inclusion criteria of the review. Two studies assessed the acute effects of sildenafil. Two small crossover study assessed the effects of long term administration. The 'acute effect' studies indicated that sildenafil has a pulmonary vasodilatory effect. The two crossover studies showed improvement in symptoms. One study showed improvement in fatigue domains from a validated health status questionnaire. Both crossover studies reported that the drug was well tolerated.
CONCLUSIONS: The validity of the observed effects is undermined by small participant numbers and inadequate exploration of the different disease etiologies. The effects on long term outcome such as NYHA functional class, symptoms, mortality and exercise capacity require further validation. More studies of adequate size are required before the long termeffects of sildenafil on clinically important outcomes can be established.»