Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial

Shenoy, Padmanabha; Kumar, Sudeep; Jha, L. K.; Choudhary, Sunil K.; Singh, Uttam; Misra, Ramnath; Agarwal, Vikas

doi:10.1093/rheumatology/keq291

Cited by 152 publications

(97 citation statements)

References 27 publications

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“…These include phosphodiesterase-5 inhibitors (sildenafi l, tadalafi l, vardenafi l) [25] and phosphodiesterase-3 inhibitors such as cilostazol. However, phosphodiesterase-5 inhibitors are being increasingly used in systemic sclerosis-related RP, with a number of recent trials [26][27][28][29] and a meta-analysis [25] suggesting benefi t, although the trials were all of short duration and large, long duration controlled trials are required. Topical nitrates have recently been revisited.…”

Section: Drug Treatmentmentioning

confidence: 99%

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

Belch

Carlizza

Carpentier

et al. 2017

Vasa

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Abstract. Regarding the clinical diagnosis of Raynaud’s phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud’s phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud’s phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment.

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Section: Drug Treatmentmentioning

confidence: 99%

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

Belch

Carlizza

Carpentier

et al. 2017

Vasa

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“…The major point to highlight in the last 18 months for the practising clinician has been the increased use of PDE5 inhibitors , and many clinicians are now very likely to use a PDE5 inhibitor as a second choice after a calcium channel blocker in patients with SScrelated RP. This is because (a) PDE5 inhibitors have now been shown to confer benefit in a number of randomised controlled trials [36,37,38,39], and in a recent meta-analysis [40] (although the trials were all short-term, with a treatment period of 6 weeks or less) and (b) reduced costs of PDE5 inhibition from previously. examine characteristics of 89 patients treated with bosentan in a 'real-world' setting: patients treated wth bosentan (median treatment duration until data collection was 17.5 months) had severe disease (61% with at least 2 previous digital ulcer episodes, and 63% had had previous intravenous iloprost infusions).…”

Section: Raynaud's Phenomenon (Which Has Not Progressed To Digital Ulmentioning

confidence: 99%

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Herrick

2016

Current Opinion in Rheumatology

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Purpose of review: Systemic sclerosis (SSc)-related digital vasculopathy can progress from severe Raynaud's phenomenon (RP) to digital ulceration, is a major cause of pain and disability, and impacts negatively on quality of life. Current treatments are often ineffective and poorly tolerated. This review summarises some of the progress which has been made in the last 12 to 18 months in terms of our understanding of disease process, measurement and treatment. Recent findings:The most important findings include that we can now better predict which patients with SSc are most likely to develop digital ulcers. In terms of treatment, a multicentre trial showed that the phosphodiesterase inhibitor sildenafil confers some benefit in SSc-related digital ulceration.Topical therapies are being explored: iontophoresis of vasodilators increases local blood flow, and in an avian model, VEGF 121 fibrin applied in a gel matrix improved wound healing. A number of challenges confront clinicians and scientists with an interest in SSc-related digital vasculopathy, specific questions being:1. What mechanisms drive the digital vasculopathy and lead to structural as well as functional change? 2. Can we predict which patients progress to digital ulceration? 3. Can we measure disease process reliably (in terms of both RP and digital ulcers), to provide outcome measures to facilitate clinical trials?4. Are we making progress in developing safe and effective treatments, for both severe RP and SScrelated digital ulceration?In this review I shall outline developments over the last 12-18 months in answering these four questions, under the headings of pathophysiology, predictors of digital ulceration, measurement of disease process, and management. Under each heading I shall consider firstly RP and secondly digital ulceration, although this is a false distinction because both are part of the spectum of SSc-digital vasculopathy. PATHOPHYSIOLOGY Raynaud's phenomenonThe pathophysiology of RP is complex and most likely involves an interplay between vascular factors, neural control mechanisms and intravascular factors [6]. Flavahan, in a recent review [7**], describes thermoregulatory mechanisms as central to an understanding of RP, highlighting the role of arteriovenous anastomoses, and how local cooling leads to increased activity of alpha 2 -adrenoceptors, resulting in reduced blood flow. In patients with SSc, structural microvascular changes mean that upstream vasoconstriction can irretrievably compromise nutritional blood flow and lead to tissue injury [7**,8]. The review also gives a framework for targetted therapeutic interventions [7**]. Digital ulcerationA commonly held view is that fingertip ulceration is ischaemic, whereas ulceration over the extensor surfaces of fingers is 'traumatic'. To date there has been very little direct evidence to support this theory. However, a study by Ruaro et al [9*] of 20 patients with SSc and fingertip ulcers demonstrated that blood flow is reduced at the site of fingertip ulcers (and improves wit...

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“…In a study of tadalafil 40 mg taken orally daily in connective tissue disease PAH, while improvement was seen over half of the participants were on therapy with bosentan at enrollment [18]. Small studies have also indicated that sildenafil and tadalafil are effective in reducing the severity of RP and promoting the healing of DU [19][20][21]. Tadalafil was used as an as add-on therapy to other vasodilators and was found to improve symptoms of RP, heal and prevent new DUs and improves quality of life in patients with resistant secondary RP [21].…”

Section: Phosphodiesterase-5 Inhibitorsmentioning

confidence: 99%

“…Small studies have also indicated that sildenafil and tadalafil are effective in reducing the severity of RP and promoting the healing of DU [19][20][21]. Tadalafil was used as an as add-on therapy to other vasodilators and was found to improve symptoms of RP, heal and prevent new DUs and improves quality of life in patients with resistant secondary RP [21]. Studies on the utility of PDE-5Is, as monotherapy and in combination with other vasodilators, for both SSc-PAH and SSc-DU are ongoing.…”

Section: Phosphodiesterase-5 Inhibitorsmentioning

confidence: 99%

Vasodilatory Therapeutics in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) Cohort

Frech

Gordon²,

Chung³

et al. 2012

Rheumatology

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The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) registry was designed to advance the understanding of the pathogenesis of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). This registry provides the opportunity to examine both microvascular and macrovascular complications in SSc. In this manuscript we review SSc-PAH therapies and report on their use in the PHAROS registry.

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Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial

Abstract: Clinicaltrials.gov, http://clinicaltrials.gov/, identifier: NCT00626665.

Cited by 152 publications

References 27 publications

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

ESVM guidelines – the diagnosis and management of Raynaud’s phenomenon

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Vasodilatory Therapeutics in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) Cohort

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