Background-Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor. Methods and Results-In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks. The primary study end point, whole blood stimulated leukotriene LTB4 at trough drug level, was reduced in all VIA-2291 groups (PϽ0.0001) in a dose-dependent fashion, with approximately 80% inhibition in Ͼ90% of patients in the 100-mg group. A significant reduction of urine leukotriene LTE4 was obtained in all dose groups. No serious adverse events were considered related to study drug. A subset of 93 patients who had undergone a 64-slice coronary CT examination at baseline continued on study medication for a total of 24 weeks and underwent a repeat scan. Five of these patients withdrew or were noncompliant and 28 had nonevaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo-treated patients and in 2 of 42 (4.8%) VIA-2291-treated patients (Pϭ0.01). A reduction in noncalcified plaque volume at 24 weeks versus placebo was observed in VIA-2291-treated groups in the 34 of these 60 patients in whom this end point was analyzable (PϽ0.01). Conclusions-VIA-2291 reduces leukotriene production at 12 weeks after an acute coronary syndrome. Preliminary data from the CT substudy suggest that such a reduction in leukotriene production may influence atherosclerosis; however, this requires confirmation in a larger study. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.
P soriasis is a chronic immune-mediated disease affecting up to 3% of the population.1 Skin and joint inflammation are the hallmarks of psoriasis and an increase in the number of T lymphocytes, antigen presenting cells, macrophages, and neutrophils is found in psoriatic plaques. 2 The complex interplay between inflammatory cells and keratinocytes induces epidermal proliferation resulting in the typical indurated, scaly, and erythematous plaques of psoriasis.3 Psoriasis has been shown to increase the risk of myocardial infarction and stroke. [4][5][6][7] Psoriasis treatments include topical corticosteroids, vitamin D analogs and phototherapy and also systemic anti-inflammatory agents, such as methotrexate, cyclosporin, or biological agents targeting tumor necrosis factor-α (TNF-α) or interleukin (IL)-12/IL-23. 8 These systemic agents all have a profound effect on skin and joint inflammation. Clinical Perspective on p 90Atherosclerosis is also an inflammatory disease. 9 We hypothesized that treatment-induced reduction in the local inflammatory process in patients with psoriasis would be associated with decreased vascular inflammation as assessed by positron emission tomography/computed tomography (PET/CT). Methods Study Design and PatientsThis was an investigator-initiated, single-center, single-blind (cardiologist and all staff involved in vascular imaging and analysis were Background-Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infarction and stroke. Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation; however, their effects on vascular inflammation are unknown. Methods and Results-This randomized, controlled trial included 30 patients with moderate to severe psoriasis and a history, or multiple risk factors, of coronary atherosclerosis. Patients were randomized (2:1) to receive either adalimumab subcutaneously for 4 months or to control nonsystemic treatment (topical therapies or phototherapy). Vascular inflammation was measured in the carotid artery and ascending aorta at baseline and week 15, by
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