A Placebo-Controlled Randomized Trial of Warfarin in Idiopathic Pulmonary Fibrosis

Noth, Imre; Anstrom, Kevin J.; Calvert, Sara B.; Andrade, Joao de; Flaherty, Kevin R.; Glazer, Craig S.; Kaner, Robert J.; Olman, Mitchell A.

doi:10.1164/rccm.201202-0314oc

Cited by 433 publications

(323 citation statements)

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“…The authors concluded that the activation of a vitamin K dependent pathway may be not beneficial and should not be a target for future therapeutic approaches in IPF. Although it has been proposed that the discrepancy between the results of the ACE-IPF study [24] and the one by KUBO et al [56] could be attributed to differences in the genetic background of the study population and in the methodology of the two studies [57], the results of the ACE-IPF study have placed, for the time being, a ''strong no'' label on the use of warfarin in IPF.…”

Section: Anticoagulantsmentioning

confidence: 93%

“…The IFIGENIA trial was a multicentre, double-blind, randomised, placebo-controlled phase III trial which evaluated the effect of a high dose of oral NAC (i.e. 600 mg three times daily) together with low dose of Pirfenidone Antifibrotic CAPACITY 1 [23] Pirfenidone Antifibrotic CAPACITY 2 [23] Pirfenidone Antifibrotic ACE-IPF [24] Warfarin Anticoagulant TOMORROW [25] BIBF 1120 Tyrosine-kinase inhibitor DANIELS [26] Imatinib mesylate Tyrosine-kinase inhibitor STEP-IPF [27] Sildenafil Phosphodiesterase-5 inhibitor BUILD-1 [28] Bosentan Endothelin-receptor antagonist BUILD-3 [29] Bosentan Endothelin-receptor antagonist ARTEMIS-IPF [30] Ambrisentan Endothelin-receptor antagonist MUSIC-IPF [31] Macitentan Endothelin-receptor antagonist RAGHU [32] IFN-c Immunomodulation INSPIRE [33] IFN-c prednisone and azathioprine compared with prednisone and azathioprine alone [20]. The primary endpoint was the change in vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLCO) at 12 months.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

“…The more recent ACE-IPF study, a double-blind, randomised, placebo-controlled trial, was set up to evaluate the efficacy and safety of warfarin in IPF [24]. The participants were randomised to receive either warfarin or placebo in a 1:1 ratio for a total of 48 weeks.…”

Section: Anticoagulantsmentioning

confidence: 99%

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Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

Αντωνίου

Margaritopoulos

Siafakas

2013

European Respiratory Review

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During the past decade important progress has been made regarding the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is the most devastating form of idiopathic interstitial pneumonia with a median survival of 3 years. The knowledge gained has been used to design multicentre, randomised, placebo-controlled trials in order to investigate agents with different mechanisms of action. Encouraging results have led to licensing of the first IPF-specific drug, pirfenidone. However, the road to successful treatment is still long. The main aim for the future should be the careful design of clinical trials, by choosing the most clinically meaningful end-point and keeping in mind that combination of various agents may be more effective. This approach has been used in the treatment of lung cancer with which IPF presents many similarities. @ERSpublications Progress toward the treatment of IPF and aims for future clinical trials

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Section: Anticoagulantsmentioning

confidence: 93%

Section: Completed Clinical Trialsmentioning

confidence: 99%

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Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

Αντωνίου

Margaritopoulos

Siafakas

2013

European Respiratory Review

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“…We believe the ACE trial does demonstrate that the coagulation cascade (or other vitamin K-dependent proteins) plays a role in IPF, in that use of warfarin did lead to worsened outcomes (2). The notion of a more selective blockade of thrombin activity is an attractive idea.…”

Section: From the Authorsmentioning

confidence: 96%

“…Indeed, the unique effects of individual members of the coagulation cascade, compared with the cascade as a whole, deserve additional respect in light of the unsuccessful AntiCoagulant Effective in Idiopathic Pulmonary Fibrosis (ACE-IPF) trial (1,2).…”

Section: From the Authorsmentioning

confidence: 99%

Reply: Rationale for Anticoagulant Therapy of Pulmonary Fibrosis

Noth

Olman

2014

Am J Respir Crit Care Med

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Interstitial Lung Disease

Maher

2024

JAMA

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ImportanceInterstitial lung disease (ILD) consists of a group of pulmonary disorders characterized by inflammation and/or fibrosis of the lung parenchyma associated with progressive dyspnea that frequently results in end-stage respiratory failure. In the US, ILD affects approximately 650 000 people and causes approximately 25 000 to 30 000 deaths per year.ObservationsThe most common forms of ILD are idiopathic pulmonary fibrosis (IPF), which accounts for approximately one-third of all cases of ILD, hypersensitivity pneumonitis, accounting for 15% of ILD cases, and connective tissue disease (CTD), accounting for 25% of ILD cases. ILD typically presents with dyspnea on exertion. Approximately 30% of patients with ILD report cough. Thoracic computed tomography is approximately 91% sensitive and 71% specific for diagnosing subtypes of ILDs such as IPF. Physiologic assessment provides important prognostic information. A 5% decline in forced vital capacity (FVC) over 12 months is associated with an approximately 2-fold increase in mortality compared with no change in FVC. Antifibrotic therapy with nintedanib or pirfenidone slows annual FVC decline by approximately 44% to 57% in individuals with IPF, scleroderma associated ILD, and in those with progressive pulmonary fibrosis of any cause. For connective tissue disease–associated ILD, immunomodulatory therapy, such as tocilizumab, rituximab, and mycophenolate mofetil, may slow decline or even improve FVC at 12-month follow-up. Structured exercise therapy reduces symptoms and improves 6-minute walk test distance in individuals with dyspnea. Oxygen reduces symptoms and improves quality of life in individuals with ILD who desaturate below 88% on a 6-minute walk test. Lung transplant may improve symptoms and resolve respiratory failure in patients with end-stage ILD. After lung transplant, patients with ILD have a median survival of 5.2 to 6.7 years compared with a median survival of less than 2 years in patients with advanced ILD who do not undergo lung transplant. Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension. In these patients, treatment with inhaled treprostinil improves walking distance and respiratory symptoms.Conclusions and RelevanceInterstitial lung disease typically presents with dyspnea on exertion and can progress to respiratory failure. First-line therapy includes nintedanib or pirfenidone for IPF and mycophenolate mofetil for ILD due to connective tissue disease. Lung transplant should be considered for patients with advanced ILD. In patients with ILD, exercise training improves 6-minute walk test distance and quality of life.

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A Placebo-Controlled Randomized Trial of Warfarin in Idiopathic Pulmonary Fibrosis

Cited by 433 publications

References 19 publications

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

Pharmacological treatment of idiopathic pulmonary fibrosis: from the past to the future

Reply: Rationale for Anticoagulant Therapy of Pulmonary Fibrosis

Interstitial Lung Disease

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