scholarly journals Meta-Analysis of Randomized Controlled Trials on Treatment of Pulmonary Arterial Hypertension

2010 ◽  
Vol 74 (7) ◽  
pp. 1458-1464 ◽  
Author(s):  
Bing He ◽  
Fengwen Zhang ◽  
Xueying Li ◽  
Chaoshu Tang ◽  
Guosheng Lin ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Pulmonary Arterial

Abstract 16011: An Outcomes Assessment of Vasodilator Therapy in Pulmonary Arterial Hypertension Through Meta-Analysis of 31 Randomized Controlled Trials

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
John J Ryan ◽  
Saurav Chatterjee ◽  
Nathan Hatton ◽  
Neel Patel ◽  
Josef Stehlik ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Mortality Benefit ◽  
Randomized Controlled ◽  
Pulmonary Vasodilators ◽  
Pulmonary Arterial

Introduction: Pulmonary Arterial Hypertension (PAH) is a rapidly progressive disease with high mortality. We reviewed randomized controlled trials (RCTs) to evaluate the effect of pulmonary vasodilators on mortality in PAH. Hypothesis: Our objective was to determine the effect of PAH medicines on survival, and the impact of trial design on outcomes. Methods: We conducted a meta-analysis using MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus (inceptions-May 2014) of all RCTs treating PAH with pulmonary vasodilators. Data on all-cause mortality and hemodynamics were abstracted. Summary relative risks (RR) and 95% confidence intervals (CI) for outcomes were calculated using a random effects model comparing various pulmonary vasodilators with control. Results: The analysis included 31 RCTs (6,271 patients, 77% female, range of mean age 30-57 years). Median follow up was 12 weeks (18 trials had ≤ 12 weeks follow up, and only 5 followed patients ≥ 6 months). When analyzed together (n = 14), FDA-approved pulmonary vasodilators demonstrated a mortality benefit with RR = 0.77 (95% CI = 0.60 - 099, I 2 = 0%). When analyzed by vasodilator type, prostacyclins were the only class of agents with significant mortality benefit, RR = 0.61 (95% CI 0.38-0.98, I 2 = 1%). Oral pulmonary vasodilators demonstrated no significant benefit on PAH mortality, RR = 0.85 (95% CI 0.65-1.12, I 2 = 0.0%), but we could not exclude a clinically meaningful benefit or harm. Many studies reported ≤1 death in at least one treatment arm. When we limited the analysis to only studies with at least 2 deaths in both treatment arms (n=9), the mortality benefit for pulmonary vasodilators was no longer significant (RR 0.86, CI 0.66-1.12, I 2 =0%), but the point estimate was below 1 and we could not exclude a reduction or increase in risk. For studies with the shorter follow up of ≤ 12 weeks, the RR of mortality for active treatment arm was 0.54 (95% CI 0.35-0.83), compared to trials with > 12 weeks of follow up where the RR of mortality was not significant at 0.91 (95% CI 0.67-1.22). Conclusion: There is an observed mortality benefit for prostacyclins in PAH. For the oral pulmonary vasodilators, there is no observed mortality benefit based on either design of trials, length of follow up or efficacy of the agents studied.

scholarly journals A meta-analysis of randomized controlled trials in pulmonary arterial hypertension

2008 ◽  
Vol 30 (4) ◽  
pp. 394-403 ◽  
Author(s):  
N. Galie ◽  
A. Manes ◽  
L. Negro ◽  
M. Palazzini ◽  
M. L. Bacchi-Reggiani ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Pulmonary Arterial

Management of pulmonary hypertension: targeted therapies

ESC CardioMed ◽  
2018 ◽  
pp. 2514-2518
Author(s):  
Nazzareno Galiè ◽  
Alessandra Manes ◽  
Massimiliano Palazzini
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Randomized Controlled Trials ◽  
Exercise Capacity ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Prostacyclin Receptor ◽  
Pulmonary Arterial

Three main signalling pathways are involved in the pathobiology of pulmonary hypertension and are targeted with specific drugs: the endothelin, the nitric oxide–cGMP, and the prostacyclin pathways. The endothelin pathway is over-activated leading to pulmonary vasoconstriction and vessel cells proliferation. Endothelin receptor antagonists are orally available drugs that counteract the endothelin detrimental effects and improve symptoms, exercise capacity, and the outcome of patients with pulmonary arterial hypertension. Phosphodiesterase type 5 inhibitors and guanylate cyclase stimulators are orally available drugs, which promote the activity of the nitric oxide pathway that is downregulated in the pulmonary vessels of pulmonary arterial hypertension patients. Different randomized controlled trials demonstrate favourable effects of these compounds on clinical, exercise, and haemodynamic parameters. Dysregulation of the prostacyclin metabolic pathways has been shown in patients with pulmonary arterial hypertension as assessed by reduction of prostacyclin synthase expression in the pulmonary arteries and of prostacyclin urinary metabolites. The clinical use of prostacyclin in patients with pulmonary arterial hypertension has been extended by the synthesis of stable analogues and by prostacyclin receptor agonists that possess different pharmacokinetic properties but share qualitatively similar pharmacodynamics effects. Prostacyclin analogues are available for intravenous, subcutaneous, inhaled, and oral administration; the prostacyclin receptor agonists are orally available. Multiple randomized controlled trials show variable efficacy of these compounds on symptoms, exercise capacity, haemodynamics, and the outcome of patients with pulmonary arterial hypertension.

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