key: cord-0906682-83pc3j15 authors: Hennekens, Charles H.; Rane, Manas; Solano, Joshua; Alter, Scott; Johnson, Heather; Krishnaswamy, Shiv; Shih, Richard; Maki, Dennis; DeMets, David L. title: Updates on hydroxychloroquine in prevention and treatment of COVID-19 date: 2021-08-23 journal: Am J Med DOI: 10.1016/j.amjmed.2021.07.035 sha: 70dc2b16422d49d60021e42ae8406b2f2dc154a0 doc_id: 906682 cord_uid: 83pc3j15 nan Professor Hennekens reports that he serves as an independent scientist in an advisory role to investigators and sponsors as Chair of data monitoring committees for Amgen, British Heart Foundation, Cadila, Canadian Institutes of Health Research, DalCor, and Regeneron; to the Collaborative Institutional Training Initiative (CITI), legal counsel for Pfizer, the United States Food and Drug Administration, and UpToDate; receives royalties for authorship or editorship of 3 textbooks and as co-inventor on patents for inflammatory markers and cardiovascular disease that are held by Brigham and Women's Hospital; has an investment management relationship with the West-Bacon Group within SunTrust Investment Services, which has discretionary investment authority; does not own any common or preferred stock in any pharmaceutical or medical device company. Our meta-analysis of hydroxychloroquine in post-exposure prophylaxis indicates a nonsignificant RR= 0.90 (95% CI 0.69 to 1.17). Thus, there is a statistically nonsignificant estimated 10% reduction in SARS-CoV-2 infection, but with sufficient precision to rule out as large as 20% reduction. Our meta-analysis of hydroxychloroquine in hospitalized patients with COVID-19 yields a nonsignificant RR= 1.10 (95% CI 0.99 to 1.23). In hospitalized patients, there is an approximate statistically nonsignificant estimated 10% increase in mortality, but with sufficient precision to rule out as small as a 1% reduction. Further, these data suggest equality, but the point estimate is in the direction of small harm on mortality. Previously, we recommended a moratorium to healthcare providers concerning prescriptions of hydroxychloroquine. (1) Since that time, no significant benefits have been found in the recent randomized evidence for post-exposure prophylaxis and among hospitalized patients. Regarding risk, hydroxychloroquine derived a reassuring safety profile from decades of prescriptions for autoimmune diseases of greater prevalence in younger and middle-aged women, whose risks of fatal outcomes due to QTc prolongations are very low. In contrast, the risks associated with COVID-19 are much higher because mortality rates for COVID-19 and the side effects of hydroxychloroquine are both highest in older patients and those with comorbidities, both of whom are predominantly men. The current totality of evidence more strongly supports our previous recommendations concerning the lack of efficacy and possible harm of hydroxychloroquine in the treatment and prevention of COVID-19. (3) Amid coronavirus threat, Americans generally have a high level of trust in medical doctors Drug diagnosis code data sought by old HH OIG may cue enforcement. Bloomberg Law Hydroxychloroquine for coronavirus: The urgent need for a moratorium on prescriptions Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro Statistical association and causation: Contributions of different types of evidence For the COVID-19 Global Rheumatology Alliance. A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19 A randomized trial of hydroxychloroquine as post exposure prophylaxis for Covid-19 A cluster-randomized trial of hydroxychloroquine as prevention of Covid-19 transmission and disease Hydroxychloroquine as postexposure prophylaxis to prevent severe acute respiratory syndrome in coronary virus 2 infection Effect of hydroxychloroquine in hospitalized patients with Covid-19 Repurposed antiviral drugs for Covid-19-Interim WHO Solidarity Trial results The need for large scale randomized evidence without undue emphasis on small trials, meta-analyses or subgroup analyses We are indebted to Thomas Fleming, PhD, Professor and Former Chair of Biostatistics, University of Washington, Seattle, for expert advice.