A Bayesian Network Meta-analysis of Add-on Drug Therapies Specific for Pulmonary Arterial Hypertension

2019 ◽  
Vol 54 (5) ◽  
pp. 423-433 ◽  
Author(s):  
Maja Petrovič ◽  
Igor Locatelli
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Meta Analysis ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Number Of Patients ◽  
All Cause Mortality ◽  
Pulmonary Arterial ◽  
Meta Analyses ◽  
Better Than

Background: Recently published meta-analyses did not discriminate between drug agents used for initial and sequential combination therapy. Objective: To assess the comparative efficacy of drugs specific for the treatment of pulmonary arterial hypertension (PAH) as add-on therapies based on 6-minute walk distance (6MWD), all-cause mortality, and discontinuation due to adverse events (AEs). Methods: EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched until December 9, 2018, for the randomized, placebo-controlled clinical trials (RCTs) conducted on primarily adult patients diagnosed with PAH. Data extracted from applicable RCTs were as follows: for 6MWD mean change from baseline, the total number of patients, and the number of patients with events, per treatment. Network meta-analysis (NMA) was conducted in a Bayesian framework. Results: A total of 16 RCTs were eligible for analysis, with 4112 patients. Add-on therapy with tadalafil or inhaled treprostinil performed better than endothelin receptor antagonists alone [27 m; 95% credible interval (CrI): (11, 43); and 19 m; 95% CrI: (10, 27); respectively]. Add-on therapy with macitentan or bosentan performed better than phosphodiesterase type 5 inhibitors alone [26 m; 95% CrI: (6.4, 45); and 22 m; 95% CrI: (5.1, 38); respectively]. Differences in all-cause mortality and discontinuation due to AEs were nonsignificant. Conclusion and Relevance: Our NMA evaluated efficacy and safety of add-on therapies in patients with PAH. None of the previous meta-analyses evaluated RCTs focusing solely on patients pretreated with another PAH-specific drug therapy. Our results support guideline recommendations on combination therapy in PAH patients and add the quantitative perspective on which sequential therapy demonstrated the greatest effect size.

Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis

2016 ◽  
Vol 4 (4) ◽  
pp. 291-305 ◽  
Author(s):  
Annie Christine Lajoie ◽  
Gabriel Lauzière ◽  
Jean-Christophe Lega ◽  
Yves Lacasse ◽  
Sylvie Martin ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Meta Analysis ◽  
Pulmonary Arterial

Combination Therapy in Pulmonary Arterial Hypertension: A Meta-Analysis

Cardiology ◽  
2011 ◽  
Vol 120 (3) ◽  
pp. 157-165 ◽  
Author(s):  
Yuanyuan Bai ◽  
Lan Sun ◽  
Shengshou Hu ◽  
Yingjie Wei
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Meta Analysis ◽  
Pulmonary Arterial

Medical Treatment of Pulmonary Arterial Hypertension

2017 ◽  
Vol 38 (05) ◽  
pp. 686-700 ◽  
Author(s):  
Sandeep Sahay ◽  
Marc Humbert ◽  
Olivier Sitbon
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Randomized Clinical Trials ◽  
Treatment Algorithm ◽  
Standard Of Care ◽  
European Respiratory Society ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
The Past ◽  
Pulmonary Arterial

AbstractPulmonary arterial hypertension (PAH) is a progressive and life-threatening disease leading to right ventricular failure and death if left untreated. Over the past two decades, progress in the understanding of pathophysiological mechanisms of the disease has led to the development of medications targeting the three major pathways of endothelial dysfunction: prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5 inhibitors. Efficacy of PAH-targeted medications has been demonstrated in monotherapy through randomized clinical trials leading to their regulatory approval. However, despite the growing numbers of available PAH-targeted medications, many patients with PAH continue to deteriorate and the disease ultimately remains fatal. The availability of multiple classes of drugs targeting different pathophysiological pathways provides strong biological rationale for the use of combination therapy in PAH. Evidence to support this strategy is growing, and many studies have demonstrated that combination therapy, administered as either a sequential or an initial regimen, can improve long-term outcomes in PAH. Treatment strategy for PAH has thereby changed significantly over the past decade, combination therapy becoming progressively the gold standard of care in patients with PAH. This is underscored by the current European Society of Cardiology/European Respiratory Society guidelines, in which combination therapy now plays a central part in the treatment algorithm.

scholarly journals Circulatory power and ventilatory power over time under goal-oriented sequential combination therapy for pulmonary arterial hypertension

2017 ◽  
Vol 7 (2) ◽  
pp. 448-454 ◽  
Author(s):  
Akihiro Hirashiki ◽  
Shiro Adachi ◽  
Yoshihisa Nakano ◽  
Yoshihiro Kamimura ◽  
Shigetake Shimokata ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Exercise Capacity ◽  
Minute Ventilation ◽  
Cardiopulmonary Exercise Testing ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Sequential Combination ◽  
Pulmonary Arterial ◽  
Circulatory Power

Many therapeutic options are available for patients with pulmonary arterial hypertension (PAH). However, little is known about the effects of sequential combination therapy on exercise capacity. Here we monitored exercise capacity by cardiopulmonary exercise testing (CPX) and observed the benefit of using a peak VO2 cutoff of 15 mL/kg/min to guide combination therapy. Thirty patients newly diagnosed with PAH were treated with goal-oriented sequential combination therapy. Endothelin receptor antagonists (ERA) were the first-line treatment, with phosphodiesterase type 5 inhibitors (PDE-5i) as the preferred combination partner. The patients underwent cardiac catheterization at baseline and after 12 months and CPX at baseline and after three, six, and 12 months. Circulatory power (CP) was defined as the product of peak O2 uptake and peak systolic blood pressure (SBP); ventilatory power (VP) was defined as peak SBP divided by the minute ventilation–CO2 production slope. After 12 months, ERA had been administered to 100% of the study patients and PDE-5i to 82%. Mean CP at baseline and after three, six, and 12 months was 1807, 2063, 2248, and 2245 mmHg·min/mL/kg, respectively, and mean VP was 2.93, 3.53, 4.16, and 3.68 mmHg, respectively. CP was greater after 6 months than at baseline ( P = 0.047); VP was greater after three months than at baseline ( P = 0.019) and further improved at six months compared with three months ( P = 0.040). Therefore, repeated CPX assessment, including measurement of CP and VP, can provide useful information regarding the efficacy of goal-oriented treatment for PAH.

Combination Therapy for Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis

2016 ◽  
Vol 32 (12) ◽  
pp. 1520-1530 ◽  
Author(s):  
Benjamin D. Fox ◽  
Osnat Shtraichman ◽  
David Langleben ◽  
Avi Shimony ◽  
Mordechai R. Kramer
Keyword(s):  
Systematic Review ◽  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Meta Analysis ◽  
Pulmonary Arterial

Comparative effectiveness of pulmonary arterial hypertension drugs in treatment-naive patients: a network meta-analysis

2020 ◽  
Vol 9 (1) ◽  
pp. 7-22
Author(s):  
Maja Petrovič ◽  
Igor Locatelli
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Marked Effect ◽  
Meta Analysis ◽  
Walking Distance ◽  
High Dose ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Treatment Naïve ◽  
Pulmonary Arterial

Aim: No network meta-analysis has been conducted to study efficacy of drug therapies specific for treatment of pulmonary arterial hypertension in treatment-naive patients only. Methods: Randomized controlled trials on pulmonary arterial hypertension-specific drug therapies were searched and a Bayesian network meta-analysis was performed. The 6-min walking distance (6MWD) and all-cause mortality were efficacy outcomes, whereas discontinuation due to adverse events was a safety-related outcome. Results: Analysis included 3.713 patients from 21 trials. Combination of ambrisentan and tadalafil showed the greatest impact on 6MWD, followed by epoprostenol and intravenous treprostinil (high dose). The latter two demonstrated marked effect size on mortality, although not statistically significant. Conclusion: According to 6MWD, ambrisentan/tadalafil combination was considered as most effective among all comparisons. Prospero ID: CRD42019110832.

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