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Channick, Richard

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Channick

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Richard

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Channick, Richard
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    Targeting the Prostacyclin Pathway with Selexipag in Patients with Pulmonary Arterial Hypertension Receiving Double Combination Therapy: Insights from the Randomized Controlled GRIPHON Study
    (Springer International Publishing, 2018) Coghlan, J. Gerry; Channick, Richard; Chin, Kelly; Di Scala, Lilla; Galiè, Nazzareno; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M.; Lang, Irene M.; McLaughlin, Vallerie; Preiss, Ralph; Rubin, Lewis J.; Simonneau, Gérald; Sitbon, Olivier; Tapson, Victor F.; Gaine, Sean
    Background: In pulmonary arterial hypertension (PAH), combination therapy is an important treatment strategy. Although randomized controlled trial data are available to support the combination of two therapies, data regarding triple combination therapy are few. Objective: The phase III GRIPHON trial enrolled 1156 patients with PAH, including 376 receiving background double combination therapy. We evaluated the efficacy and safety of selexipag as a third agent in these patients and further analyzed this subgroup according to symptom burden at baseline as indicated by World Health Organization (WHO) functional class (FC). Methods: In this post hoc analysis, hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using Cox proportional-hazard models to determine response to selexipag versus placebo on the composite primary endpoint of morbidity/mortality. Baseline characteristics and adverse events were summarized descriptively. Results: Of 376 patients receiving background endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE-5i) therapy, 115 had WHO FC II symptoms and 255 had WHO FC III symptoms at baseline. The impact on the primary endpoint of adding selexipag versus placebo to double combination therapy was consistent with the effect in the overall population (HR 0.63; 95% CI 0.44–0.90) as well as in patients with WHO FC II and III symptoms. Compared with the overall population, discontinuations due to an adverse event were higher when selexipag was added to background double combination therapy; no safety concerns were identified. Conclusion: The addition of selexipag to background double combination therapy with an ERA and PDE-5i provides an incremental benefit similar to that seen in the overall population, including in patients with WHO FC II or III symptoms at baseline. ClinicalTrials.gov Identifier NCT01106014. Electronic supplementary material The online version of this article (10.1007/s40256-017-0262-z) contains supplementary material, which is available to authorized users.
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    Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension
    (European Respiratory Society, 2017) Gaine, Sean; Chin, Kelly; Coghlan, Gerry; Channick, Richard; Di Scala, Lilla; Galiè, Nazzareno; Ghofrani, Hossein-Ardeschir; Lang, Irene M.; McLaughlin, Vallerie; Preiss, Ralph; Rubin, Lewis J.; Simonneau, Gérald; Sitbon, Olivier; Tapson, Victor F.; Hoeper, Marius M.
    Patients with connective tissue disease-associated pulmonary arterial hypertension (PAH-CTD) have a poor prognosis compared with other aetiologies. The underlying CTD can influence treatment response and outcomes. We characterised the GRIPHON study PAH-CTD subgroup and evaluated response to selexipag. Of 334 patients with PAH-CTD, PAH was associated with systemic sclerosis (PAH-SSc) in 170, systemic lupus erythematosus (PAH-SLE) in 82 and mixed CTD/CTD-other in 82. For the primary composite endpoint of morbidity/mortality, hazard ratios (HR) and 95% CI were calculated using Cox proportional hazard models. Compared with the overall GRIPHON population, the CTD subgroup was slightly older with a greater proportion of females and shorter time since diagnosis. Patients with PAH-SSc appeared to be more impaired at baseline, with a more progressive disease course. The converse was observed for PAH-SLE. Selexipag reduced the risk of composite morbidity/mortality events in patients with PAH-CTD by 41% (HR 0.59; 95% CI 0.41–0.85). Treatment effect was consistent irrespective of baseline PAH therapy or CTD subtype (interaction p=0.87 and 0.89, respectively). Adverse events were predominately prostacyclin-related and known for selexipag treatment. GRIPHON has allowed the comprehensive characterisation of patients with PAH-CTD. Selexipag delayed progression of PAH and was well-tolerated among PAH-CTD patients, including those with PAH-SSc and PAH-SLE.
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    Leaflet Area as a Determinant of Tricuspid Regurgitation Severity in Patients With Pulmonary Hypertension
    (Ovid Technologies (Wolters Kluwer Health), 2015) Afilalo, J.; Grapsa, J.; Nihoyannopoulos, P.; Beaudoin, J.; Gibbs, J. S. R.; Channick, Richard; Langleben, D.; Rudski, L. G.; Hua, L.; Handschumacher, M. D.; Picard, Michael; Levine, Robert
    Background: Tricuspid regurgitation (TR) is a risk factor for mortality in pulmonary hypertension (PH). TR severity varies among patients with comparable degrees of PH and right ventricular (RV) remodeling. The contribution of leaflet adaptation to the pathophysiology of TR has yet to be examined. We hypothesized that tricuspid leaflet area (TLA) is increased in PH, and that its size relative to RV remodeling determines TR severity. Methods and Results: A prospective cohort of 255 patients with PH from pre- and post-capillary etiologies was assembled from two centers. Patients underwent a 3-D echocardiogram focused on the tricuspid apparatus. TLA was measured with the Omni custom software package. Compared with normal controls, PH patients had a twofold increase in RV volumes, 62% increase in annulus area, and 49% increase in TLA. Those with severe TR demonstrated inadequate increase in TLA relative to the closure area, such that the ratio of TLA-to-closure area <1.78 was highly predictive of severe TR (odds ratio 68.7; 95% CI 16.2, 292.7). The median vena contracta width was 8.5 mm in the group with small TLA and large closure area as opposed to 4.8 mm in the group with large TLA and large closure area. Conclusions: TLA plays a significant role in determining which patients with PH develop severe functional TR. The ratio of TLA-to-closure area, reflecting the balance between leaflet adaptation vs. annular dilation and tethering forces, is an indicator of TR severity that may identify which patients stand to benefit from leaflet augmentation during tricuspid valve repair.