More evidence for combination therapy benefits in PAH

By Eleanor McDermid

Another meta-analysis adds to evidence of increased benefits for patients with pulmonary arterial hypertension (PAH) who are given combination therapy.

A meta-analysis published last month found a reduced risk of clinical worsening among patients given combination therapy. And the latest meta-analysis, published in CHEST, shows benefits for a range of individual clinical indicators, including 6-minute walk distance, functional class and haemodynamics.

However, combination therapy was associated with "a much higher incidence of withdrawal due to adverse effects than monotherapy", the researchers.

Indeed, patients taking combination therapy were twice as likely to halt treatment as those taking a single agent.

The team analysed a total of 6702 patients from 35 randomised controlled trials, 15 of which included patients taking combination therapy.

In the pooled analysis, patients were a significant 1.65-fold more likely to improve their functional class if they took combination therapy versus monotherapy and they improved their 6-minute walk distance by an additional 19.96 metres.

Cardiopulmonary haemodynamics also improved, with pulmonary vascular resistance and mean pulmonary artery pressure falling by an additional 187 dyn/sec per cm⁵ and 4.81 mmHg, respectively, and there was a nonsignificant improvement in cardiac index.

But like the authors of the previous meta-analysis, Zhong-ning Zhu (Hebei Medical University, Shijiazhuang, China) and colleagues did not find significantly improved mortality among patients given combination therapy versus monotherapy, although they also note that most studies of combination therapy were relatively short.

"Thus, the effect of these drugs on long-term mortality and duration of survival improvement is uncertain", they caution.

However, their analysis did confirm that PAH-specific monotherapy resulted in a significant halving of patients' mortality risk relative to placebo or conventional treatment. And this effect persisted when they excluded studies involving intravenous epoprostenol, with a significant 43% mortality reduction remaining for oral treatments.

Likewise, monotherapy and PAH-specific therapy in general showed significant benefits for patients' functional class, 6-minute walk distance and haemodynamics.

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