Journal of internal medicine
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Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post-translational modification to pyruvamide-Ang II (Ang P) by pyridoxal-5'-phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B6 derivative and, therefore, could be a cost-effective drug against hypertension. ⋯ PLP induces a post-translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B6 might reduce blood pressure in hypertensive patients, PLP might be a cost-effective drug against hypertension.
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Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials. ⋯ In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs.
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Hereditary angioedema (HAE) is a rare, potentially life-threatening genetic disorder characterized by recurrent attacks of swelling. Local vasodilation and vascular leakage are stimulated by the vasoactive peptide bradykinin, which is excessively produced due to dysregulation of the activated factor XII (FXIIa)-driven kallikrein-kinin system. There is a need for novel treatments for HAE that provide greater efficacy, improved quality of life, minimal adverse effects, and reduced treatment burden over current first-line therapies. ⋯ We highlight that there is a range of FXIIa inhibitors in development for different therapeutic areas. Of these, garadacimab, an FXIIa-targeted inhibitory monoclonal antibody, is the most advanced and has shown potential as a novel long-term prophylactic treatment for patients with HAE in clinical trials. The evidence from these trials is summarized and discussed, and we propose areas for future research where targeting FXIIa may have therapeutic potential beyond HAE.