Patients with pulmonary arterial hypertension (PAH) had similar efficacy and safety profile when taking either oral Treprostinil or selexipag, indicating that Treprostinil would be an adequate replacement.
Differences in 6-minute walking distance (6MWD), adverse events, and clinical worsening reduction were non-existent between oral Treprostinil and selexipag. According to the review published in the International Journal of Cardiology, this should indicate that Treprostinil can be used to treat pulmonary arterial hypertension (PAH) with the same efficacy and safety as selexipag.
PAH is a disease that has a median survival of 7 years, even with several treatments becoming available in the past several years. Although prostacyclin is the most powerful treatment for PAH, complications can arise from how the medication is delivered. Oral therapies using analogs for prostacyclin may be able to avoid these complications. This review aimed to compare oral therapies that target the prostacyclin pathway in patients with PAH.
The researchers used MEDLINE, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov to look for studies to include in the review. All studies had to be randomized controlled trials (RCTs) through May 2020. The RCTs had to include a comparison between selexipag, oral Treprostinil, or beraprost with a placebo and had to be published in English. Studies were excluded if they were non-randomized studies, were retrospective or editorial, included patients that had prostacyclin analogs before enrollment, and included patients with PAH groups that were different from idiopathic, heritable, drugs and toxin-induced, PAH associated with connective tissue or HIV or repaired congenital disease.
The main outcomes included a change in 6MWD, death, and time to clinical worsening (TTCW). The researchers were also looking for safety outcomes, including headache, diarrhea, jaw pain, nasopharyngitis, and nausea. Data from each study were extracted, including trial information, patient demographics, and etiology of PAH.
Eight RCTs were included in the review, 4 of which compared oral Treprostinil with placebo, 2 of which compared selexipag with placebo, and 2 that compared beraprost with placebo. There were 3023 patients across the studies that were included: 828 in the Treprostinil group, 607 in selexipag, 125 in beraprost, and 1463 who had placebo. Most patients (62.7%) had idiopathic/hereditary PAH whereas 25.6% had PAH associated with connective tissue disease.
Beraprost was found to have a risk ratio (RR) of 0.65 (95% CI, 0.11-3.89) for death compared with an RR of 0.93 (95% CI, 0.43-1.97) in oral Treprostinil when both were compared with placebo. The 6MWT was significantly increased in both the Treprostinil and beraprost groups compared with placebo; beraprost had the greatest improvement (weighted mean differential [WMD], 21.98; 95% CI, 5.0536-38.9063) but Treprostinil also had improvement (WMD, 9.05; 95% CI, 3.0280-15.0839). A non-significant increase in 6MWT was associated with selexipag (WMD, 15.41; 95% CI, –0.6074 to 31.4232); there was no significant difference in 6MWT change between the 3 medications.
Selexipag had lowered the risk of clinical worsening significantly compared with placebo (RR, 0.47; 95% CI, 0.35-0.65); Treprostinil also had a similar reduction of risk (RR, 0.65; 95% CI, 0.46-0.90). Beraprost had a non-significant reduction in the lowering of risk (RR, 0.70; 95% CI, 0.36-1.38). There was also no significant difference in the reduction of the outcome of clinical worsening between Treprostinil and selexipag.
Beraprost led to less frequent adverse events compared with selexipag and Treprostinil, specifically in jaw pain, nausea, headache, nasopharyngitis, and diarrhea. However, there were no significant differences between Treprostinil and selexipag in terms of safety profile.
There were some limitations to this review. None of the studies compared all 3 treatments to each other directly. The discontinuation rate could have limited the potential effect of each of the 3 treatments. A new oral prostanoid, ralinepag, was not included in any of the studies due to its lack of evidence.
The researchers concluded that the meta-analysis should be able to help “physicians in the difficult task of deciding which might be the best oral drug targeting the prostacyclin pathway to prescribe in patients with non-severe PAH having an unsatisfactory response to the first-line therapy.” They concluded that Treprostinil could be an option in place of selexipag in some patients with PAH.
Reference
Manzi G, Mariana MV, Filomena D, et al. Comparative effectiveness of oral therapies targeting the prostacyclin pathway in pulmonary arterial hypertension: a systematic review and network meta-analysis. Int J Cardiol. Published online December 27, 2023. doi:10.1016/j.ijcard.2023.131691
Initiating BP Medication Linked to Higher Fall, Fracture Risks in Nursing Home Residents
May 2nd 2024Among over 60,000 nursing home residents who initiated antihypertensive medication, rates of excess fractures due to falls per 100 person-years were as high as 5 among certain patient groups, such as those with dementia and high blood pressure (BP).
Read More
Reducing Time Sitting Can Help Lower BP in Older Adults, Randomized Trial Finds
April 20th 2024The randomized trial found that reducing sitting time over a 6-month period was association with reduced systolic blood pressure (BP) among a group of older patients with obesity and high rates of hypertension.
Read More
Targeting MACC1 Offers Promising Therapeutic Strategy for PAH
April 10th 2024Positive responses seen following experiments involving metastasis-associated in colon cancer 1 (MACC1) indicate that the biomarker can be used to better diagnose and treat patients with pulmonary arterial hypertension (PAH).
Read More
Pandemic Care Gaps Associated With Loss of Hypertension Control, Study Finds
April 3rd 2024Surprisingly, the investigators found people with uncontrolled hypertension before the pandemic actually had a slightly higher chance of getting their blood pressure under control during the crisis.
Read More