A meta-analysis of trials of pulmonary hypertension: A clinical condition looking for drugs and research methodology

Macchia, Alejandro; Marchioli, Roberto; Marfisi, RosaMaria; Scarano, Marco; Levantesi, Giacomo; Tavazzi, Luigi; Tognoni, Gianni

doi:10.1016/j.ahj.2007.02.037

Cited by 206 publications

(162 citation statements)

References 38 publications

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“…Conventional meta-analyses are limited by estimates between two interventions compared directly with each other, precluding assessment of comparative efficacy and safety of all available interventions. [4][5][6][7] Hence, evidence regarding the best treatment, either alone or in combination, is limited, leaving such decisions to individual clinical judgment. 8,9 A network meta-analysis approach can bridge this gap and guide both clinical decision-making and future research.…”

Section: Registration: Prospero Crd42016036803mentioning

confidence: 99%

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Jain

Khera

Girotra

et al. 2017

Chest

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BACKGROUND:We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacologic interventions for pulmonary arterial hypertension (PAH).METHODS: MEDLINE, the Cochrane Register, EMBASE, CINAHL, and clinicaltrials.gov were searched (January 1, 1990 to March 3, 2016. Randomized controlled trials (RCTs) studying the approved pharmacologic agents endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), the oral/inhaled (PO/INH) and IV/subcutaneous (SC) prostanoids, and riociguat and selexipag, alone or in combination, for pulmonary arterial hypertension (PAH) and reporting at least one efficacy outcome were selected.RESULTS: Thirty-one RCTs with 6,565 patients were selected. In network meta-analysis, when compared with a median placebo rate of 14.5%, clinical worsening was estimated at 2.8% with riociguat (risk ratio [RR], 0.19; 95% CI, 0.05-0.76); at 3.9% with ERA þ PDE5i (RR, 0.27; 95% CI, 0.14-0.52), and at 5.7% with PDE5i (RR, 0.39; 95% CI, 0.24-0.62). For improvement in functional status, when compared with 16.2% in the placebo group, improvement in at least one New York Heart Association/World Health Organization (NYHA/WHO) functional class was estimated at 81.8% with IV/SC prostanoids (RR, 5.06; 95% CI, 2.3211.04), at 28.3% with ERA þ PDE5i (RR, 1.75; 95% CI, 1.05-2.92), and at 25.2% with ERA (RR, 1.56; 95% CI, 1.22-2.00). Differences in mortality were not significant. Adverse events leading to discontinuation of therapy were highest with the PO/INH prostanoids (RR, 2.92; 95% CI, 1.68-5.06) and selexipag (RR, 2.06; 95% CI, 1.04-3.88) compared with placebo.CONCLUSIONS: Currently approved pharmacologic agents have varying effects on morbidity and functional status in patients with PAH. Future comparative effectiveness trials are warranted with a focus on a patient-centered approach to therapy. REGISTRATION: PROSPERO CRD42016036803CHEST 2017; 151(1):90-105 KEY WORDS: comparative efficacy; network meta-analysis; pulmonary arterial hypertension ABBREVIATIONS: 6MWD = 6-min walk distance; ERA = endothelin receptor antagonist; FDA = Food and Drug Administration; GRADE = Grading of Recommendations Assessment, Development, and Education; NYHA = New York Heart Association; PAH = pulmonary arterial hypertension; PDE5i = phosphodiesterase-5 inhibitor; RCT = randomized controlled trial; RR = risk ratio; SUCRA = surface under the cumulative ranking area; WHO = World Health Organization; WMD = weighted mean difference Pulmonary arterial hypertension (PAH) or World Health Organization (WHO) group 1 pulmonary hypertension is a progressive disease associated with significant morbidity and a 5% to 15% annual mortality rate. [1][2][3] In recent years, a number of drug classes to treat PAH have been approved for clinical use. These include endothelin receptor antagonists (ERA), phosphodiesterase-5 inhibitors (PDE5i), parenteral and nonparenteral prostacyclins, a soluble guanylate cyclase stimulator, and a prostacyclin-receptor agonist. Although randomized ...

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Section: Registration: Prospero Crd42016036803mentioning

confidence: 99%

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Jain

Khera

Girotra

et al. 2017

Chest

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“…11,12 Endothelial dysfunction with dysregulation of vasodilation and vasoconstriction, in combination with loss of the antithrombotic and prothrombotic equilibrium, are hallmarks of PAH. 7 The pulmonary vasculature in PAH is ill suited to adjust to the increases in blood volume during pregnancy and hemodynamic changes after delivery.…”

Section: Discussionmentioning

confidence: 99%

“…7 and quality of life and survival 8 in non-pregnant women. In individuals responsive to epoprostenol, a survival advantage can be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

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Epoprostenol treatment for idiopathic pulmonary arterial hypertension in pregnancy

et al. 2010

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Idiopathic pulmonary arterial hypertension is a rare condition associated with significant maternal mortality. We report the management of a 37-year-old multigravida with severe disease using epoprostenol, a multidisciplinary approach, and a planned delivery. Although the patient survived the pregnancy, her pulmonary function significantly worsened. Epoprostenol, a pulmonary vasodilator, should be considered when indicated during pregnancy. Neither fetal nor neonatal harm was identified.

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“…One was reported in 2007 which included 16 RCT and 1962 patients. 91 According to their results, limited benefits were achieved for clinical end points, but no significant survival advantage could be demonstrated. A more recent meta-analysis addressed the all-cause mortality and survival.…”

Section: Meta-analyses Of Drug Therapymentioning

confidence: 99%

Pulmonary hypertension—“state of the art” management in 2012

Saxena

2012

Indian Heart Journal

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A B S T R A C TPulmonary artery hypertension (PAH) is a pathological condition of small pulmonary arteries, characterised by vascular proliferation and remodelling. The pulmonary artery pressure and pulmonary vascular resistance progressively rise, leading to right heart failure and death. Pulmonary artery hypertension may be secondary to various conditions, or it may be idiopathic where no underlying cause is identifiable. Earlier, only symptomatic treatment was available for such patients which did not change the natural history of the disease. However, over the years, improvement in understanding the pathogenesis has resulted in the development of targeted approaches to the treatment of PAH. Survival advantage has also been shown with some of the pharmacologic agents. This review article discusses the current management strategy for PAH with special emphasis on an idiopathic variety, in an Indian context.

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A meta-analysis of trials of pulmonary hypertension: A clinical condition looking for drugs and research methodology

Cited by 206 publications

References 38 publications

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Epoprostenol treatment for idiopathic pulmonary arterial hypertension in pregnancy

Pulmonary hypertension—“state of the art” management in 2012

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