Sequential combination therapy improves clinical and functional status in PAH

A new investigation revealed that sequential combination therapy (SCT) was recommended in patients with WHO-FC II-III PAH who have established background therapy. The study was published in the journal "Pulmonary Pharmacology & Therapeutics, 2022." 

Pulmonary arterial hypertension (PAH) is a life-threatening cardiopulmonary disease characterized by pulmonary vasculature remodeling leading to right heart failure and premature death. Research done in the past on PAH combination therapy pooled sequential and initial combination therapies together which might threaten their authenticity and clinical significance due to the difference between the two strategies. Hence researchers conducted a meta-analysis to find the efficacy and safety of sequential combination therapy for pulmonary arterial hypertension. 

Using search strategy in databases like PubMed, Embase, and the Cochrane Library all the randomized controlled trials that compared sequential combination therapy (SCT) with background therapy (BT) in PAH patients were searched. Raw data were extracted to calculate risk ratio (RR) or weighted mean difference (WMD) for predefined efficacy and safety outcomes. Mantel-Haenszel fixed or random effects model was used based on heterogeneity. 

Results: 

• 17 RCTs involving 4343 patients (97.2% of patients with WHO-FC II-III) were included.
• SCT decreased clinical worsening, nonfatal clinical worsening, functional class (decrease of 28% in the portion of patients with WHO-FC worsening and increase of 33% in the portion of patients with WHO-FC improvement), and increased 6-min walk distance, but didn't reduce mortality, lung transplantation, admission to hospital, and treatment escalation compared with BT.
• Although any adverse events and serious adverse events were similar between SCT and BT, SCT increased all-cause treatment discontinuation and drug-related treatment discontinuation with a higher incidence of headache, flushing, nausea, diarrhea, and jaw pain.  

Thus, the researchers recommended sequential combination therapy for WHO-FC II-III PAH patients who have established background therapy to improve clinical worsening, functional status, and exercise capacity. But they also added that a higher incidence of side effects and withdrawal may be seen. 

For the full article, click here: doi:10.1016/j.pupt.2022.102144

Tan Z, Wu PY, Zhu TT, Su W, Fang ZF. Efficacy and safety of sequential combination therapy for pulmonary arterial hypertension: A meta-analysis of Randomized-Controlled Trials [published online ahead of print, 2022 Jul 30]. Pulm Pharmacol Ther. 2022;102144.