PAH Review Finds Combination Therapy Superior to Monotherapy in Reducing Clinical Worsening

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by Patricia Silva PhD |

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The use of a combination therapy in patients with pulmonary arterial hypertension (PAH) “significantly” reduced the risk of clinical worsening compared to monotherapy in those responding to treatment, according to a recent meta-analysis published in the journal The Lancet, titled “Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis.

Several drugs targeting the endothelial dysfunction associated with PAH have emerged over the past 20 years. Licensed PAH-specific therapies include phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostaglandins, soluble guanylate cyclase stimulators, and selective prostacyclin receptor agonists. Randomized controlled trials and previous meta-analysis, however, reported conflicting data concerning the effect of combined targeted therapy in comparison with monotherapy for PAH treatment.

Annie Christine Lajoie, MD, of the Pulmonary Hypertension Research Group and Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center in Canada, and colleagues performed a systematic review and meta-analysis to investigate the effects of a combination of PAH-specific therapies in comparison to monotherapy on predefined clinical worsening in PAH. The researchers searched for relevant articles published between 1990 and 2015. Of the 2017 studies identified by the researchers, 17 (comprising 4,095 patients) were included in the analysis, and 15 of them, evaluating clinical worsening, were included in the primary analysis.

Researchers found that combined therapy in patients was associated with significant risk reduction for clinical worsening compared with monotherapy. Although the Eggers test showed a possible publication bias favoring positive data, the researchers determined that the risk ratio was nearly the same when four studies with positive results were removed. They also observed no heterogeneity between studies.

“Combining PAH-targeted therapies significantly reduced the risk of clinical worsening, as predefined in clinical studies, for patients with PAH. This effect was generally consistent across subgroups,” the researchers wrote, according to a press release. “Combination therapy also reduced the risk for admission to hospital, treatment escalation, and symptomatic progression, and resulted in improved patient functional status.”

The team, however, also noted that “many patients still had clinical worsening with combination therapy, [and] identification of innovative therapeutic targets for PAH is thus urgently needed.”

PAH is a life-threatening disease characterized by a progressive increase in pulmonary vascular resistance, ultimately leading to right-heart failure.