Can Mineralocorticoid Receptor Antagonism Counteract Cardiometabolic Long-term Effects of Steroids? (MiRACCLES study)

Metabolic syndrome and cardiovascular diseases (CVDs) represent the major cause of morbidity and mortality globally. According to the World Health Organisation, more people die annually from CVDs than from any other cause. Hormones underpin the pathophysiological changes surrounding the disease progression. Steroids such as prednisolone are one of the most widely prescribed and effective therapeutics for a variety of inflammatory and autoimmune conditions including inflammatory arthritis, arteritis, asthma, sarcoidosis and nephritis due to their powerful anti-inflammatory effects, but benefits are limited by serious cardiometabolic adverse effects. To date, there is no established specific means to counteract the cardiometabolic complications. There is strong evidence in animals that the adverse cardiometabolic effects of steroids are mediated by closely-related hormone receptors called mineralocorticoid receptors (MRs) which are present on fat cells, heart and immune cells, and that blockade of MRs (MR antagonism) protects against steroid-induced cardiometabolic complications while maintaining the anti-inflammatory benefit. This body of work will define, for the first time in humans, the therapeutic potential of MR antagonism to counteract steroid-induced adverse metabolic and cardiac complications, and provide novel evidence for paradigm shifts in the management of patients exposed to excess steroids.