Real-world ambrisentan safety profile as expected
medwireNews: Analysis of the VOLibris Tracking (VOLT) post-marketing registry shows no new safety issues for ambrisentan used in patients with pulmonary arterial hypertension (PAH).
The adverse events observed were “consistent with that reported previously in clinical trials”, say Jean-Luc Vachiéry (Hôpital Erasme, Cliniques Universitaires De Bruxelles, Belguim) and co-researchers, and therefore also consistent with the current EU labelling of ambrisentan.
At the time of analysis, the registry, which covers 115 centres in 15 countries from Europe, Canada and Australia, contained data on 998 patients who had received at least one dose of ambrisentan, taking it for an average of 2.2 patient–years.
Most (85%) patients started ambrisentan at a dose of 5 mg/day, with 15% receiving 10 mg/day, the team reports in The Journal of Heart and Lung Transplantation. By the end of follow-up or patient withdrawal the corresponding proportions were 63% and 36%.
The primary safety endpoint was elevation of alanine aminotransferase or aspartate aminotransferase to more than three times the upper limit of normal. These each occurred at a rate of 2% and the upper limit of the 95% confidence interval was less than 3%, meaning neither occurred significantly more frequently than “the assumed background incidence” of 1.5%.
The most common adverse events of special interest during treatment were oedema/fluid retention in 25% of patients, anaemia in 14% and heart failure in 13%. Peripheral oedema was the event that most often led to discontinuation, at 4%, and heart failure was the most frequent nonfatal serious adverse event, occurring in 8% of patients.
The patients were aged an average of 59.5 years and 67% were women. Idiopathic PAH was the most frequent subtype, at 45%, followed by associated PAH, at 42%, with connective tissue disease (CTD) accounting for more than half of these cases.
The frequency of adverse events in patients with CTD-PAH was similar to that in the overall population, except for anaemia, which occurred at a more frequent 22% in the CTD-PAH patients.
In all, 22% of the study population had not previously received PAH-specific medication. The researchers highlight that these patients presented with advanced symptoms, “despite increased disease awareness and availability of treatment options.”
Eight percent of the treatment-naïve subgroup were categorised as World Health Organisation functional class IV at presentation, and 65% as class III. At least half of these patients had been diagnosed within 1 year before enrolment in the registry. Safety of ambrisentan in these patients was no different to that in the overall population.
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