Effects of sildenafil on maximum walking time in patients with arterial claudication: The ARTERIOFIL study

Omarjee, Loukman; Pabic, Estelle Le; Custaud, Marc‐Antoine; Fontaine, Cédric; Locher, Clara; Renault, Alain; Jaquinandi, Vincent; Azzola, Vincent; Barbeau-Terrier, Céline; Laporte, Isabelle; Ripoche, Manuela; Onillon, Yoanna; Chrétien, Jean-Marie; Daniel, Valérie; Barca, Juan-Manuel Chao de la; Homedan, Chadi; Reynier, Pascal; Ábrahám, Pierre

doi:10.1016/j.vph.2019.05.003

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…Reports of improvements in walking distance in patients with both limb and buttock claudication following sildenafil therapy support the potential for PDE5I therapy to benefit patients with peripheral arterial disease (Omarjee, Le Pabic et al, 2019). In a similar fashion to the angiogenic potential of PDE5Is demonstrated in experimental stroke models, preclinical studies have demonstrated improvements in vascular perfusion, tissue blood flow, and vascular density with sildenafil (Senthilkumar, Smith et al, 2007) and vardenafil (Sahara, Sata et al, 2010) in a mouse model of unilateral hindlimb ischaemia.…”

Section: Emerging Therapeutic Uses Of Pde Type 5 Inhibitorsmentioning

confidence: 93%

“…Significant improvement in maximal walking time but no significant effects on pain-free walking time and oxygenation parameters (Omarjee, Le Pabic et al, 2019). Ongoing.…”

Section: Sildenafilmentioning

confidence: 95%

“…In a similar fashion to the angiogenic potential of PDE5Is demonstrated in experimental stroke models, preclinical studies have demonstrated improvements in vascular perfusion, tissue blood flow, and vascular density with sildenafil (Senthilkumar, Smith et al, 2007) and vardenafil (Sahara, Sata et al, 2010) in a mouse model of unilateral hindlimb ischaemia. Recently, a prospective crossover study of 12 patients reported a significant improvement in maximal walking time with a single oral dose of sildenafil, although this did not impact pain‐free walking time or skin tissue oxygenation during exercise (Omarjee, Le Pabic et al, 2019). Further prospective studies investigating the impact of PDE5I treatment on clinical outcomes are ongoing (Table 3).…”

Section: Emerging Therapeutic Uses Of Pde Type 5 Inhibitorsmentioning

confidence: 99%

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Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease

Tzoumas

Farrah

Dhaun

et al. 2020

British J Pharmacology

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PDE type 5 inhibitors (PDE5Is), such as sildenafil, tadalafil and vardenafil, are a class of drugs used to prolong the physiological effects of NO/cGMP signalling in tissues through the inhibition of cGMP degradation. Although these agents were originally developed for the treatment of hypertension and angina, unanticipated side effects led to advances in the treatment of erectile dysfunction and, later, pulmonary arterial hypertension. In the last decade, accumulating evidence suggests that PDE5Is may confer a wider range of clinical benefits than was previously recognised. This has led to a broader interest in the cardiovascular therapeutic potential of PDE5Is, in conditions such as hypertension, myocardial infarction, stroke, peripheral arterial disease, chronic kidney disease and diabetes mellitus. Here, we review the pharmacological properties and established licensed uses of this class of drug, along with emerging therapeutic developments and possible future indications. 1 | INTRODUCTION Few other pharmaceutical agents have had a history as serendipitous as the class of PDE type 5 inhibitors (PDE5Is; Figure 1). Developed over 30 years ago, initially for cardiovascular indications, PDE5Is emerged as a revolutionary treatment for erectile dysfunction (ED), licensed in 1998 (Goldstein, Lue et al., 1998). Further investigation of their effects on pulmonary arterial pressure culminated in their approval for the treatment of pulmonary arterial hypertension (PAH) in 2005 (Galiè, Ghofrani et al., 2005). Early reports of fatal cardiovascular events in patients prescribed a PDE5I delayed wider research into their therapeutic benefits, but it soon became apparent that these adverse events reflected the complex nature of patients initially receiving the drug and their high level of cardiovascular risk, rather than the properties of the drug itself (Cheitlin, Hutter et al., 1999;

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Section: Emerging Therapeutic Uses Of Pde Type 5 Inhibitorsmentioning

confidence: 93%

“…Significant improvement in maximal walking time but no significant effects on pain-free walking time and oxygenation parameters (Omarjee, Le Pabic et al, 2019). Ongoing.…”

Section: Sildenafilmentioning

confidence: 95%

Section: Emerging Therapeutic Uses Of Pde Type 5 Inhibitorsmentioning

confidence: 99%

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Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease

Tzoumas

Farrah

Dhaun

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

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“…The Sildenafil Efficacy Study on Time Walk From Peripheral Arterial Disease Patients (Stade II) With Arterial Claudication (ARTERIOFIL) [32] was a small single-centre RCT, assessing the effects of a single 100 mg oral dose of sildenafil vs. placebo on clinical symptoms among patients with PAD and intermittent claudication. It was found that sildenafil significantly increased maximal walking time (300 s vs. 402 s; P < 0.01), but had no significant effects on pain-free walking time as compared to the placebo [32]. The Efficiency of Sildenafil on the Absolute Claudication Distance of Peripheral Arterial Disease Patients With Intermittent Claudication (VIRTU-OSE) study [32] is an ongoing multicentre RCT to evaluate the long-term effect of sildenafil in symptomatic patients with PAD.…”

Section: Sildenafilmentioning

confidence: 99%

Review new concepts in pharmacotherapy for peripheral arterial disease

Kotalczyk

Vallabhaneni

Lip

2021

Current Opinion in Cardiology

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Purpose of reviewTo provide an overview of new concepts in the pharmacotherapy of patients with peripheral artery disease (PAD).Recent findingsModern therapeutic strategies for patients with PAD include specific symptom management and multidisciplinary prevention of cardiovascular events. Low-dose rivaroxaban in combination with aspirin improves outcomes compared with aspirin monotherapy among patients with PAD. Other novel concepts include the use of bosentan, vorapaxar or sildenafil among symptomatic patients with PAD. Likewise, lipid-lowering therapy reduces the risk of major cardiovascular and limb events.SummaryPersonalized management, identification of risk factors and shared-decision making are crucial in improving the best medical therapy for patients with PAD. Further studies are needed to assess the long-term safety and efficacy of novel strategies in real-world patients.

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“…A single dose of sildenafil (100 mg) improved the maximum walking time of patients with arterial claudication [68]. Eight weeks of treatment with sildenafil (100 mg/day) in patients with Raynaud’s phenomenon secondary to systemic sclerosis increased finger blood flow both before and after exposure to cold [69].…”

Section: Beneficial Effects Of Sildenafil In Cardiovascular Systemmentioning

confidence: 99%

Sildenafil beyond erectile dysfunction and pulmonary arterial hypertension: Thinking about new indications

Ala

Jafari

Dehpour

2020

Fundamemntal Clinical Pharma

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Sildenafil, approved two decades ago, is the inhibitor of phosphodiesterase 5 (PDE5). First of all, it was designated for angina pectoris, but soon it showed a wonderful efficacy in erectile dysfunction (ED) and then pulmonary arterial hypertension (PAH). Due to the distribution of phosphodiesterase (PDE) in almost all organs, maybe it effects other diseases. Hence, a great number of investigations began to understand the role of PDEi in different organs. Preliminary research on sildenafil in cell culture and animal models has yielded promising results. Soon, a greater number of animal researches and clinical trials joined them. The results disclosed sildenafil can have beneficial effects in each organ such as heart, liver, kidney, brain, and intestines. Furthermore, it has significantly improved the prognosis of organ ischemia in various animal models. Clinical trials in several diseases, such as recurrent spontaneous miscarriage, fatty liver disease, bronchopulmonary dysplasia (BPD), heart failure, and premature ejaculation (PE) brought promising results. Although some clinical trials are available on the effects of sildenafil on various diseases, further studies on humans are needed to consolidate the ultimate effects of sildenafil. The aim of this review was to describe the effects of sildenafil on each organ and explain its mechanisms of action. Further, other PDE inhibitors such as tadalafil and vardenafil have been briefly discussed in parts of this review.

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Effects of sildenafil on maximum walking time in patients with arterial claudication: The ARTERIOFIL study

Cited by 8 publications

References 45 publications

Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease

Established and emerging therapeutic uses of PDE type 5 inhibitors in cardiovascular disease

Review new concepts in pharmacotherapy for peripheral arterial disease

Sildenafil beyond erectile dysfunction and pulmonary arterial hypertension: Thinking about new indications

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