Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease

Galiè, Nazzareno; Denton, Christopher P.; Dardi, Fabio; Manes, Alessandra; Mazzanti, G.; Li, Baohui; Varanese, Lucio; Esler, Anne; Harmon, Cathi; Palazzini, Massimiliano

doi:10.1016/j.ijcard.2017.02.094

Cited by 14 publications

(10 citation statements)

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“…With regard to RCTs, a total of 801 articles were identified through our comprehensive search strategy (see Supplementary Figure 1, available on the Arthritis & Rheumatology website at http://onlinelibrary.wiley.com/doi/10.1002/art.41669/abstract) and 11 studies were ultimately included in the meta‐analysis (as listed in Supplementary Table 4 on the Arthritis & Rheumatology website at http://onlinelibrary.wiley.com/doi/10.1002/art.41669/abstract). Among those that met the criteria for one of the defined primary end points, 5 RCTs reported time to clinical morbidity/mortality events (12–16,23,24) (specifically defined in Supplementary Table 1 [http://onlinelibrary.wiley.com/doi/10.1002/art.41669/abstract]), and 6 RCTs reported change in the 6MWD (10,11,25–30). The 11 RCTs enrolled a total of 4,329 patients with PAH, including 1,267 patients with CTD‐PAH (29.3%).…”

Section: Resultsmentioning

confidence: 99%

“…In the overall PAH population, additional PAH therapy led to a placebo‐ or monotherapy‐corrected increase in the 6MWD (mean increase of 28.6 meters, 95% CI 19.2, 38.0; P < 0.001) (Figure 2A). In 8 RCTs (total of 2,874 patients; 882 with CTD‐PAH [31%]), this end point was reported according to CTD‐PAH etiology (9–12,15,23–30). Additional PAH therapy led to an increase in the 6MWD in the overall PAH population (mean increase of 34.6 meters, 95% CI 22.1, 47.1; P < 0.001) and in patients with CTD‐PAH (mean increase of 20.4 meters, 95% CI 10.9, 29.9; P < 0.001) (Figures 2B and C).…”

Section: Resultsmentioning

confidence: 99%

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Long‐Term Outcomes in Patients With Connective Tissue Disease–Associated Pulmonary Arterial Hypertension in the Modern Treatment Era: Meta‐Analyses of Randomized, Controlled Trials and Observational Registries

Khanna

Zhao

Saggar

et al. 2021

Arthritis & Rheumatology

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Objective. Data on the magnitude of benefit of modern therapies for pulmonary arterial hypertension (PAH) in connective tissue disease (CTD)-associated PAH are limited. In this study, we performed meta-analyses of randomized, controlled trials (RCTs) and registries to quantify the benefit of these modern therapies in patients with CTD-PAH.Methods. The PubMed and Embase databases were searched for articles reporting data from RCTs or registries published between January 1, 2000 and November 25, 2019. Eligibility criteria included multicenter studies with ≥30 CTD-PAH patients. For an RCT to be included, the trial had to evaluate an approved PAH therapy, and long-term risks of clinical morbidity and mortality or 6-minute walk distance had to be reported. For a registry to be included, survival rates had to be reported. Random-effects models were used to pool the data.Results. Eleven RCTs (total of 4,329 patients; 1,267 with CTD-PAH) and 19 registries (total of 9,739 patients; 4,008 with CTD-PAH) were included. Investigational therapy resulted in a 36% reduction in the risk of clinical morbidity/ mortality events both in the overall PAH population (hazard ratio [HR] 0.64, 95% confidence interval [95% CI] 0.54, 0.75; P < 0.001) and in CTD-PAH patients (HR 0.64, 95% CI 0.51, 0.81; P < 0.001) as compared to control subjects. The survival rate was lower in CTD-PAH patients compared to all PAH patients (survival rate 62%, 95% CI 57, 67% versus 72%, 95% CI 69, 75% at 3 years). The survival rate in CTD-PAH patients treated primarily after 2010 was higher than that in CTD-PAH patients treated before 2010 (survival rate 73%, 95% CI 62, 81% versus 65%, 95% CI 59, 71% at 3 years).Conclusion. Modern therapy provides a similar reduction in morbidity/mortality risk in patients with CTD-PAH when compared to the PAH population overall. Risk of death is higher in CTD-PAH patients than in those with PAH overall, but survival has improved in the last 10 years, which may be related to increased screening and/ or new treatment approaches. Early detection of PAH in patients with CTD and up-front intensive treatment are warranted.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Long‐Term Outcomes in Patients With Connective Tissue Disease–Associated Pulmonary Arterial Hypertension in the Modern Treatment Era: Meta‐Analyses of Randomized, Controlled Trials and Observational Registries

Khanna

Zhao

Saggar

et al. 2021

Arthritis & Rheumatology

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“…Inhibition of the cyclic guanosine monophosphate (cGMP) degrading enzyme phosphodiesterase type-5 (PDE5) results in vasodilation through increasing the local bioavailability of nitric oxide. PDE5 inhibitors approved for the treatment of SSc-PAH are sildenafil (SUPER-1 and SUPER-2 trials) [70,71] and tadalafil (PHIRST-1 and PHIRST-2 trials) [72,73]. Riociguat is an approved guanylate cyclase stimulator which augments the NO-cGMP pathway [74].…”

Section: Drugs Therapies For Ssc-pahmentioning

confidence: 99%

An Overview of Different Techniques for Improving the Treatment of Pulmonary Hypertension Secondary in Systemic Sclerosis Patients

et al. 2022

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In systemic sclerosis (SSc) mortality is mainly linked to lung involvement which is characterized by interstitial lung disease (ILD) and pulmonary hypertension (PH). In SSc, PH may be due to different etiologies, including ILD, chronic thromboembolic disease, pulmonary veno-occlusive disease, and pulmonary arterial hypertension (PAH). The main tool to screen PAH is transthoracic echocardiography (TTE), which has a sensitivity of 90%, even if definitive diagnosis should be confirmed by right heart catheterization (RHC). The radiological evaluation (i.e., HRTC) plays an important role in defining the possible causes and in monitoring the evolution of lung damage. For PAH, identifying individuals who have borderline elevation of pulmonary arterial pressure needs to be appropriately managed and followed. In the past few years, the strategy for the management of PAH has significantly evolved and new trials are underway to test other therapies. This review provides an overview of the tools to evaluate PAH in SSc patients and on treatment options for these patients.

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“…Similarly, PHIRST-1/PHIRST-2 demonstrated that tadalafil improves 6MW distance, quality of life, and reduces clinical worsening in a PAH population that included CTD-PAH patients. Although, treatment with tadalafil in patients with CTD-PAH was less efficacious than in patients with IPAH [86,87]. Despite the lack of a trial designed to explicitly assess the effect of this medication class in SSc-PAH patients, their cost, ease of administration, improvement in healing and prevention of development of digital ulcers [52], and tolerability make these agents ideal for first-line therapy in SSc-PAH.…”

Section: Phosphodiesterase Inhibitorsmentioning

confidence: 99%

Systemic Sclerosis-Associated Pulmonary Hypertension: Spectrum and Impact

Naranjo

Hassoun

2021

Diagnostics

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Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a catastrophic complication of one of the most common and devastating autoimmune diseases. Once diagnosed, it becomes the leading cause of mortality among this patient population. Screening modalities and risk assessments have been designed and validated by various organizations and societies in order to identify patients early in their disease course and promptly refer them to expert centers for a hemodynamic assessment and formal diagnosis. Moreover, several large multicenter clinical trials have now included patients with SSc-PAH to assess their response to therapy. Despite an improved understanding of the condition and significant advances in supportive and targeted therapy, outcomes have remained far from optimal. Therefore, rigorous phenotyping and search for novel therapies are desperately needed for this devastating condition.

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Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease

Cited by 14 publications

References 10 publications

Long‐Term Outcomes in Patients With Connective Tissue Disease–Associated Pulmonary Arterial Hypertension in the Modern Treatment Era: Meta‐Analyses of Randomized, Controlled Trials and Observational Registries

Long‐Term Outcomes in Patients With Connective Tissue Disease–Associated Pulmonary Arterial Hypertension in the Modern Treatment Era: Meta‐Analyses of Randomized, Controlled Trials and Observational Registries

An Overview of Different Techniques for Improving the Treatment of Pulmonary Hypertension Secondary in Systemic Sclerosis Patients

Systemic Sclerosis-Associated Pulmonary Hypertension: Spectrum and Impact

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