Higher risk of mortality for children with PAH on a higher dose of the medicine

Dr. Oliver Miera (picture: private)

Some people with a congenital heart defect suffer from high blood pressure in their lungs, technically referred to as pulmonary arterial hypertension. This can manifest itself for instance through shortness of breath, giddiness and a decreased exercise tolerance. Revatio® containing sildenafil is one of the medicines used to treat this condition. The manufacturer Pfizer recently tested the active substance for the first time in a large-scale clinical study with children to determine which dose is best for which body weight.

After completing the study, Pfizer announced in October 2011 that there was a higher rate of mortality among children with pulmonary arterial hypertension (PAH) if a higher dose of the medicine Revatio® was administered than recommended by the manufacturer.  

We asked Dr. Oliver Miera, paediatric cardiologist and assistant medical director at the Deutsches Herzzentrum Berlin, what families with children with a congenital heart defect and PAH should know about the medicine.

Dr. Miera, what is the medicine Revatio® used for in patients with a congenital heart defect?

Revatio® can lower high blood pressure in the lungs. We know from studies with adults that the medicine is effective in lowering pulmonary arterial hypertension and thus results in the person affected living for longer. There are different heart defects in which PAH occurs as a secondary disease and where the medicine is applied to make patients more resilient.

Do you still maintain that the medicine is safe?

Yes, we do because as a result of the study, we can now give an exact recommendation on the best dose for children – which is precisely the reason why the study was carried out. This is of fundamental importance, as we previously had to calculate the dose for children by taking the dose recommended for adults as a basis and then calculating it down to the child’s body weight. But that is not particularly exact because children’s bodies process medicine differently.

Most children with PAH and weighing between 20-45 kg are treated with the recommended normal dose of 20 mg three times a day. Children from the age of one weighing less than 20 kg are given a dose of 10 mg three times a day.

Administering a higher dose might still be indicated in individual cases, but this should be critically examined in view of the latest study results. The benefits and the risk must be carefully considered on a case-by-case basis and discussed individually with the parents and patients.

A study was also carried out with sildenafil by the Competence Network for Congenital Heart Defects. Do young people and parents have any reason for concern after finding out the results of the study?

No, they don’t because the patients who took part in the Competence Network study with sildenafil were treated with the recommended dose of 20 mg sildenafil three times a day. That is the optimum dose according to the latest findings.

About the disease

Pulmonary arterial hypertension (PAH) is the definition for various forms of increased blood pressure in the blood vessels of the lungs. It can arise without a known cause or as a result of a congenital heart defect. If recognised in good time and depending on the type of heart defect, it can be rectified by a heart catheter intervention or a heart operation. Medicinal therapies are available and aim to reduce pulmonary pressure and resistance in order to increase the blood flow through the lungs. In very severe cases of PAH, a lung transplantation or a heart-lung transplantation is necessary.