Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial

Simonneau, Gérald; D’Armini, Andrea Maria; Ghofrani, Hossein Ardeschir; Grimminger, Friedrich; Jansa, Pavel; Kim, Nick H.; Mayer, Eckhard; Pulido, Tomás; Wang, Chen; Colorado, Pablo; Fritsch, Arno; Meier, Christian; Nikkho, Sylvia; Hoeper, Marius M.

doi:10.1016/s2213-2600(16)30022-4

Cited by 132 publications

(149 citation statements)

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“…The soluble guanylate cyclase stimulator riociguat has shown efficacy and is the only pharmacotherapy approved for the treatment of inoperable CTEPH and persistent/recurrent CTEPH [1,[25][26][27][28]. An emerging interventional technique for the management of inoperable CTEPH is percutaneous balloon pulmonary angioplasty (BPA), which aims to dilate the pulmonary artery branches through the inflation of a small balloon inserted into the artery.…”

Section: Introductionmentioning

confidence: 99%

An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan

et al. 2017

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Epidemiological data for chronic thromboembolic pulmonary hypertension (CTEPH) are limited and there are conflicting reports regarding its pathogenesis.A literature review was conducted to identify CTEPH epidemiological data up to June 2014. Data were analysed to provide estimates of the incidence of CTEPH in the USA, Europe and Japan. An epidemiological projection model derived country-specific estimates of future incidence and diagnosis rates of CTEPH.Overall, 25 publications and 14 databases provided quantitative epidemiological data. In the USA and Europe, the crude annual incidence of diagnosed pulmonary embolism and crude annual full (i.e. diagnosed and undiagnosed) incidence of CTEPH were 66-104 and 3-5 cases per 100 000 population, respectively, while in Japan these rates were lower at 6.7 and 1.9 per 100 000 population, respectively. In 2013, 7-29% of CTEPH cases in Europe and the USA were diagnosed, and the majority of patients were in New York Heart Association functional class III/IV at diagnosis. The projection model indicated that incidence of CTEPH will continue to increase over the next decade.These data suggest that CTEPH is underdiagnosed and undertreated, and there is an urgent need to increase awareness of CTEPH. High-quality epidemiological studies are required to increase understanding of CTEPH.

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Section: Introductionmentioning

confidence: 99%

An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan

et al. 2017

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“…After 12 weeks of open-label use of riociguat, the patients previously receiving placebo in CHEST-1 achieved a similar improvement in 6MWD to those in the extended riociguat treatment arm. 17 The CHEST-2 mortality results can be contrasted with those of Scholzel et al in an observational study of patients with inoperable CTEPH treated with PDE-5 inhibitors, endothelin receptor antagonists, prostacyclin analogs, or a combination of these. 18 In this study, 32 patients were followed over a mean time period of 3.4 years.…”

mentioning

confidence: 99%

Treatment of Chronic Thromboembolic Pulmonary Hypertension: The Role of Medical Therapy and Balloon Pulmonary Angioplasty

Fernandes

Poch

Auger

2016

Methodist DeBakey Cardiovascular Journal

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Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially curable disease when treated with pulmonary thromboendarterectomy (PTE). However, even at experienced surgical centers, nearly one-third of patients with CTEPH will be deemed inoperable for reasons including distal disease, comorbidities, or out-of-proportion pulmonary hypertension. It is in these patients with inoperable CTEPH that pulmonary hypertension (PH)-targeted medical therapy and balloon pulmonary angioplasty have potential therapeutic value.Previous unblinded cohort trials have assessed PH-targeted medical therapy in various subpopulations of CTEPH patients using epoprostenol, treprostinil, sildenafil, bosentan, and iloprost, each demonstrating measurable pulmonary hemodynamic effects. However, riociguat, a soluble guanylate cyclase stimulator, is the first FDA-approved therapy for inoperable CTEPH to demonstrate both an improvement in functional capabilities (6-minute walk time) as well as significant gains in secondary pulmonary hemodynamic end points in a large placebo-controlled trial.Balloon pulmonary angioplasty is an interventional procedure using telescoping catheters placed in the pulmonary arteries, through which wires and balloons are used to mechanically disrupt chronic clot material and relieve pulmonary vascular obstruction. Contemporary case series from multiple centers worldwide have demonstrated pulmonary hemodynamic improvement with this approach.As a result of these advances, patients with inoperable CTEPH who had few options as recently as 5 years ago now have alternatives with emerging evidence of therapeutic efficacy.

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“…Riociguat is generally well tolerated and has a similar good safety profile in patients with CTEPH and in patients with treatment-naïve or pretreated PAH 7,45,47,50,51,57. Most AEs are related to the mechanism of action of riociguat34 and are of mild-to-moderate intensity 7,45.…”

Section: Safetymentioning

confidence: 99%

“…In a final analysis of CHEST-2 conducted at the March 2014 data cutoff, 172 patients were ongoing, 171 had received ≥2 years of treatment, and 18 patients had switched to the commercial drug 51. At 2 years, the improvement in 6MWD was maintained, FC had improved in 39% of patients, and the estimated survival was 93%.…”

Section: Clinical Trialsmentioning

confidence: 99%

Riociguat: a soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension

Lian

Jiang

Jing

2017

DDDT

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Despite advances in treatments and improved survival, patients with pulmonary hypertension still experience poor exercise and functional capacity, which has a significant detrimental impact on their quality of life. The nitric oxide (NO)–soluble guanylate cyclase (sGC)–cyclic guanosine 3′,5′-monophosphate (cGMP) pathway has been shown to play an important role in cardiovascular physiology, especially in vasodilation and pulmonary vascular tone. The oral sGC stimulator riociguat has a dual mode of action on the NO–sGC–cGMP pathway: direct stimulation of sGC independent of NO and indirect simulation via sensitization of sGC to endogenous NO. Riociguat is now licensed in >50 countries worldwide, including in Europe, the USA, Canada, and Japan. Approval for the treatment of pulmonary arterial hypertension (PAH) was based on Phase III data from the PATENT studies, in which riociguat significantly improved exercise capacity, pulmonary vascular resistance, a range of secondary end points, and hemodynamic parameters in patients with symptomatic PAH. In the Phase III CHEST studies, riociguat consistently improved exercise capacity in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy and is now the only drug to be approved for this indication. Riociguat was well tolerated in long-term studies of PAH and CTEPH. This review describes the role of the NO–sGC–cGMP pathway in the pathophysiology of pulmonary hypertension, and reviews the clinical efficacy and safety of riociguat in patients with PAH and inoperable or persistent/recurrent CTEPH. Based on its demonstrated efficacy and established safety profile, riociguat is a promising treatment option for patients with PAH and CTEPH.

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Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial

Cited by 132 publications

References 28 publications

An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan

An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan

Treatment of Chronic Thromboembolic Pulmonary Hypertension: The Role of Medical Therapy and Balloon Pulmonary Angioplasty

Riociguat: a soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension

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