Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna; Williams, Trevor; Celermajer, David S.; Sahhar, Joanne; Wong, Peter; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jérémy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

doi:10.1136/bmjopen-2016-011028

Cited by 17 publications

(11 citation statements)

References 73 publications

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“…1 An Australian multicenter RCT SPHInx evaluating the administration of apixaban vs. placebo in SSc-PAH is currently ongoing. 73 Ongoing clinical trials…”

Section: Anticoagulationmentioning

confidence: 99%

Pulmonary arterial hypertension in connective tissue disorders: Pathophysiology and treatment

Zanatta

Polito

Famoso

et al. 2019

Exp Biol Med (Maywood)

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Pulmonary arterial hypertension (PAH) is a serious complication of connective tissue disorders (CTDs), and CTD-PAH is the second cause of PAH after the idiopathic form. PAH is characterized by increased pulmonary arterial pressure and pulmonary vascular resistance, which can lead to right heart failure and death. About 90% of CTD-PAH cases are associated with systemic sclerosis (SSc, 74%), mixed connective tissue disease (MCTD, 8%) or systemic lupus erythematosus (SLE, 8%). CTD-PAH has also been reported, albeit rarely, in Sjögren syndrome, inflammatory idiopathic myopathies and rheumatoid arthritis. As for idiopathic PAH, the impaired production of vasoactive mediators such as nitric oxide and prostacyclin, and the increased production of vasoconstrictors and proliferative mediators such as endothelin-1, affect the vascular tone and promote vascular remodeling. Moreover, there is growing evidence suggesting that inflammation and autoimmunity may contribute to the genesis and progression of CTD-PAH, especially in SLE and MCTD patients who require an early administration of corticosteroids and immunosuppressants in order to avoid irreversible pathologic changes in pulmonary vessels. Conversely, immunosuppressive agents are ineffective in SSc-PAH, which requires a timely and aggressive treatment with specific PAH therapies (combination therapy). In this review, we summarized the current data on the pathophysiology and treatment of CTD-PAH. Impact statement Our article focuses on the pathogenesis and treatment of CTD-PAH. In the latest ESC/ESR guidelines for PAH, the authors underline that although CTD-PAH should follow the same treatment protocol as idiopathic PAH, the therapeutic approach is more complex and difficult in the former. This review throws light on several peculiar aspects of CTD-PAH and the latest findings in the pathogenesis, namely, the role of inflammation in the maladaptive right ventricle remodeling in SSc-PAH where immunosuppressants are classically believed to be ineffective. Furthermore, we discuss the major critical points in the therapy of CTD-PAH which is one of the strengths of our article. To the best of our knowledge, there are no other reviews that exclusively focus on the pathogenesis and treatment of CTD-PAH patients, with an emphasis on the more critical issues. Thus, it is our contention that our work would be of interest to the readers.

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“…1 An Australian multicenter RCT SPHInx evaluating the administration of apixaban vs. placebo in SSc-PAH is currently ongoing. 73 Ongoing clinical trials…”

Section: Anticoagulationmentioning

confidence: 99%

Pulmonary arterial hypertension in connective tissue disorders: Pathophysiology and treatment

Zanatta

Polito

Famoso

et al. 2019

Exp Biol Med (Maywood)

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“…The SPHYNX trial aims to assess the efficacy, safety, and cost-effectiveness of treatment with apixaban in PAH associated with scleroderma over 3 years, in a multicenter, double-blind, placebo-controlled randomized controlled trial. 42 Of note, the SPHYNX trial includes a cost-effectiveness analysis, and will be able to infirm the results of a previous medico-analytic study which suggested a positive effect of anticoagulant therapy in patients with idiopathic PAH but not PAH associated with scleroderma. 43 The Pragmatic Clinical Trials in Scleroderma Note: The table shows a summary of data obtained from prospective studies, regarding the efficacy and safety of anticoagulant therapy in patients with pulmonary arterial hypertension (PAH) orchronic thromboembolic pulmonary hypertension (CTEPH).…”

Section: Unmet Needs Recent Advances Ongoing Studies Determining Thmentioning

confidence: 88%

Use of Anticoagulants in Patients with Pulmonary Hypertension

2020

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Since the earliest works on the understanding of different forms of pulmonary hypertension, thrombosis has been involved in the pathophysiology of the disease, both in pulmonary arterial hypertension (PAH) and in chronic thromboembolic pulmonary hypertension (CTEPH). Autopsy and then pathophysiological data paved the way for the use of anticoagulants as a treatment for PAH and CTEPH. In PAH their role has diminished with the advent of specific targeted therapies, but they are still prescribed in more than half of PAH patients, because of concomitant venous thromboembolism or atrial fibrillation. In CTEPH long-term anticoagulant therapy is the cornerstone of the management. The recent development of direct oral anticoagulants (DOACs) raises the question of the best anticoagulation strategy, both in patients with PAH and in patients with CTEPH. In this review, we present an overview of the history of anticoagulants in the management of patients suffering from PAH or CTEPH, an update of the available data on the underlying rationale of their use in these subjects, an alert on the potential risks of using DOACs in these poorly explored situations, and the setting up of dedicated trials to evaluate the best anticoagulant treatment strategies in patients suffering from PAH or CTEPH.

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“…48 There is an ongoing trial (SPHInX) that aims to evaluate the efficacy and safety of apixaban, a direct oral anticoagulant, in SSc-PAH. 100…”

Section: Oral Anticoagulationmentioning

confidence: 99%

<p>Management of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis</p>

Almaaitah¹,

Highland²,

Tonelli³

2020

IBPC

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Systemic sclerosis (SSc) is a rare and complex immune-mediated connective tissue disease characterized by multi-organ fibrosis and dysfunction. Systemic sclerosisassociated pulmonary arterial hypertension (SSc-PAH) is a leading cause of death in this population. Pulmonary arterial hypertension (PAH) can coexist with other forms of pulmonary hypertension in SSc, including pulmonary hypertension related to left heart disease, interstitial lung disease, chronic thromboembolism and pulmonary venous occlusive disease, which further complicates diagnosis and management. Available pulmonary arterial hypertension therapies target the nitric oxide, endothelin and prostacyclin pathways. These therapies have been studied in SSc-PAH in addition to idiopathic PAH, often with different treatment responses. In this article, we discuss the management as well as the treatment options for patients with SSc-PAH.

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Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

Cited by 17 publications

References 73 publications

Pulmonary arterial hypertension in connective tissue disorders: Pathophysiology and treatment

Pulmonary arterial hypertension in connective tissue disorders: Pathophysiology and treatment

Use of Anticoagulants in Patients with Pulmonary Hypertension

<p>Management of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis</p>

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