Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and antiinflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus disease 2019 (COVID-19). Finally, current literature associated with hydroxychloroquine and COVID-19 has been analyzed to interrelate the mechanisms, adverse effects, and use of hydroxychloroquine in the current pandemic. Currently, there is insufficient evidence about the efficacy and safety of hydroxychloroquine in COVID-19. KEY MESSAGES 1. HCQ, initially an antimalarial agent, is used as an immunomodulatory agent for managing several autoimmune diseases, for which its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions. 2. HCQ is generally well-tolerated although severe life-threatening adverse effects including cardiomyopathy and conduction defects have been reported. 3. HCQ use in COVID-19 should be discouraged outside clinical trials under strict medical supervision.
BackgroundDigoxin use has been associated with a lower risk of 30‐day all‐cause admission and readmission in patients with heart failure and reduced ejection fraction (HFrEF).HypothesisDigoxin use will be associated with improved outcomes in patients with HFrEF receiving β‐blockers.MethodsOf the 3076 hospitalized Medicare beneficiaries with HFrEF (EF <45%), 1046 received a discharge prescription for β‐blockers, of which 634 were not on digoxin. Of the 634, 204 received a new discharge prescription for digoxin. Propensity scores for digoxin use, estimated for each of the 634 patients, were used to assemble a matched cohort of 167 pairs of patients receiving and not receiving digoxin, balanced on 30 baseline characteristics. Matched patients (n = 334) had a mean age of 74 years and were 46% female and 30% African American.Results30‐day all‐cause readmission occurred in 15% and 27% of those receiving and not receiving digoxin, respectively (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.31‐0.83, P = 0.007). This beneficial association persisted during 4 years of follow‐up (HR: 0.72, 95% CI: 0.57‐0.92, P = 0.008). Digoxin use was also associated with a lower risk of the combined endpoint of all‐cause readmission or all‐cause mortality at 30 days (HR: 0.54, 95% CI: 0.34‐0.86, P = 0.009) and at 4 years (HR: 0.76, 95% CI: 0.61‐0.96, P = 0.020).ConclusionsIn hospitalized patients with HFrEF receiving β‐blockers, digoxin use was associated with a lower risk of 30‐day all‐cause readmission but not mortality, which persisted during longer follow‐up.
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