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

Lajoie, Annie C.; Lauzière, Gabriel; Lega, Jean‐Christophe; Lacasse, Yves; Martin, S. Clark; Simard, Serge; Bonnet, Sébastien; Provencher, Steeve

doi:10.1016/s2213-2600(16)00027-8

Cited by 206 publications

(185 citation statements)

References 45 publications

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“…58,59 However, the direct meta-analyses in the published literature synthesized evidence informing about either the pooled effect of drug therapy on relevant outcomes 4,7 or the effect of combination vs monotherapy as a whole without addressing the role of individual agents. 60,61 They do not provide composite evidence incorporating all available data to assess the comparative effectiveness of different drug therapies in improving specific outcomes. By synthesizing evidence from existing trials to analyze both direct and indirect treatment comparisons, our network meta-analysis provides comprehensive evidence in which therapyspecific relative risks are comparable across classes.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, medication safety and tolerability, as assessed by adverse events leading to discontinuation, were least favorable for nonparenteral prostanoids, consistent with the results of a recent meta-analysis. 60 Hence, this provides evidence against their role as primary therapy in the management of PAH. Their suggested role as "ancillary therapy" in clinical guidelines would need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Future comparative efficacy trials are, therefore, warranted to make definitive conclusions. Third, similar to previous PAH meta-analyses, 4,7,60,61 our analysis is somewhat limited by the small number of RCTs available for each drug; we had to combine the effect of multiple agents in a drug class. It is possible that the efficacy of agents is drug specific rather than class specific.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Jain

Khera

Girotra

et al. 2017

Chest

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“…More than 10 drugs targeting the endothelin, nitric oxide, and prostacyclin pathways (3) have been developed and commercialized. At present, available therapies have been shown to decrease patients' risk of short-term mortality (4) and clinical worsening (5). However, despite these advances with modern treatment modalities, most patients continue to experience poor quality of life (6,7), and long-term prognosis remains poor (8)(9)(10).…”

mentioning

confidence: 99%

Translating Research into Improved Patient Care in Pulmonary Arterial Hypertension

Bonnet

Provencher

Guignabert

et al. 2017

Am J Respir Crit Care Med

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120

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“…Several trials have been conducted which evaluated the efficacy of drug combination therapy compared to monotherapy. A recent meta-analysis on 15 RCTs, with combination of PAH-specific therapies (upfront and sequential add-ons) compared with PAH-specific monotherapy, showed a risk reduction for clinical worsening of 17 versus 28%, respectively [66]. A similar outcome was observed by a meta-analyses from Fox et al [67] on 18 RCTs.…”

Section: Combination Therapymentioning

confidence: 58%

Pulmonary Hypertension in Systemic Sclerosis

Poelkens¹,

Vonk²,

Ede³

2017

Systemic Sclerosis

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The main cause of death in systemic sclerosis is interstitial lung disease, followed by pulmonary hypertension (PH). Pulmonary hypertension is the result of microvasculopathy which is caused by a disrupted healing process of endothelin damage and is featured by vasoconstriction, proliferation of arterial wall, inflammation, and fibrosis. Reclassification of pulmonary hypertension has led to five distinctive groups. In systemic sclerosis, patients may suffer from pulmonary artery hypertension (PAH, group 1), pulmonary hypertension due to interstitial lung disease (group 3), cardiac disease (group 2), and/ or thromboembolic pulmonary hypertension (group 4). Patients endure declining performance during exercise, but symptoms may be variable and nonspecific. Diagnosis is made by right heart catheterization. To select patients for this invasive procedure, several screening tools are discussed, including N-terminal pro-brain natriuretic peptide levels, uric acid levels, spirometry and diffusing capacity for carbon monoxide (DCLO), echocardiography (ECG), and the DETECT algorithm. Depending on features such as disease duration, presence of anti-centromere antibodies, and DCLO, three different flow charts for screening are presented. Based on pathophysiology, several medical treatments have been developed like prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and stimulation of the nitric oxide pathway. Combination therapy as well as lung transplantation and supportive therapy is discussed.

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

Cited by 206 publications

References 45 publications

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Comparative Effectiveness of Pharmacologic Interventions for Pulmonary Arterial Hypertension

Translating Research into Improved Patient Care in Pulmonary Arterial Hypertension

Pulmonary Hypertension in Systemic Sclerosis

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