Current vascular pharmacology
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Curr Vasc Pharmacol · Jan 2017
ReviewThrombotic Management of Antiphospholipid Syndrome: Towards Novel Targeted Therapies.
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. ⋯ Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS.
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Curr Vasc Pharmacol · Jan 2017
ReviewOral Glucose-lowering Drugs and Cardiovascular Outcomes: From the Negative RECORD and ACCORD to Neutral TECOS and Promising EMPA-REG.
Cardiovascular (CV) morbidity and mortality are higher among patients with diabetes mellitus type 2 (T2DM), particularly those with concomitant CV diseases, compared with other populations. In patients with T2DM, intensive glucose lowering reduces microvascular disease, but has a smaller and debated effect on CV events or mortality. In this setting, the US Food and Drug Administration (FDA) required in 2008 that all new agents for the treatment of T2DM should be evaluated in terms of CV safety. Metformin has long been established as first-line pharmacological therapy in patients with T2DM, due to its proven beneficial CV effects. Despite the controversies about the issue of the CV safety of other oral antidiabetic agents such as sulfonylureas (SUs) and thiazolidinediones (TZDs), long-term randomized trials suggested neutral effects of these agents on macrovascular disease. Moreover, there are a number of CV outcome trials designed to determine the long-term CV safety of new glucose-lowering agents, like dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium glucose cotransporter 2 (SGLT2) inhibitors. Although the results of these trials indicate the CV safety of oral new antidiabetic agents, only one of them (with empagliflozin) has so far reported reduction of CV events. Recently, LEADER (Liraglutide Effect And Action in Diabetes: Evaluation of Cardiovascular Outcome Results - A Long-term Evaluation), a CV outcome trial in diabetic patients by using an injectable glucose-lowering agent (liraglutide) has also reported a reduction in CV outcomes. ⋯ The present review considers the long-term CV effects of anti-diabetic drugs and updates the relevant randomized CV outcome studies of oral glucose-lowering agents.
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Curr Vasc Pharmacol · Jan 2017
ReviewRenoprotective Effects of SGLT2 Inhibitors: Beyond Glucose Reabsorption Inhibition.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that inhibit glucose and sodium reabsorption at proximal tubules. These drugs may exhibit renoprotective properties, since they prevent the deterioration of the glomerular filtration rate and reduce the degree of albuminuria in patients with diabetes-associated kidney disease. ⋯ However, it has been hypothesized that the most important mechanisms for this phenomenon include the reduction in the intraglomerular pressure, the changes in the local and systemic degree of activation of the renin-aldosterone-angiotensin system and a shift in renal fuel consumption towards more efficient energy substrates such as ketone bodies. The beneficial effects of SGLT2 inhibitors on various aspects of renal function make them an attractive choice in patients with (and possibly without) diabetes-associated renal impairment.