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0 0.5 1 1.5 2+ Mortality 65% Improvement Relative Risk Mortality (b) 25% Mortality (c) 57% HCQ for COVID-19  Falcone et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? PSM prospective study of 315 patients in Italy Lower mortality with HCQ (not stat. sig., p=0.2) Falcone et al., Open Forum Infectious .., Nov 2020 Favors HCQ Favors control

Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study

Falcone et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563
Nov 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 421 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk:
RR 0.35, p = 0.2, propensity score matched
RR 0.75, p = 0.36, multivariate Cox regression
RR 0.43, p < 0.001, univariate Cox regression
risk of death, 65.0% lower, RR 0.35, p = 0.20, treatment 40 of 238 (16.8%), control 30 of 77 (39.0%), NNT 4.5, adjusted per study, PSM.
risk of death, 25.0% lower, RR 0.75, p = 0.36, treatment 40 of 238 (16.8%), control 30 of 77 (39.0%), NNT 4.5, adjusted per study, multivariate Cox regression.
risk of death, 57.0% lower, RR 0.43, p < 0.001, treatment 40 of 238 (16.8%), control 30 of 77 (39.0%), NNT 4.5, adjusted per study, univariate Cox regression.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Falcone et al., 19 Nov 2020, prospective, propensity score matching, Italy, peer-reviewed, 19 authors, average treatment delay 6.5 days.
This PaperHCQAll
Role of Low-Molecular-Weight Heparin in Hospitalized Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study
MD Marco Falcone, Giusy Tiseo, Greta Barbieri, Valentina Galfo, Alessandro Russo, Agostino Virdis, Francesco Forfori, Francesco Corradi, Fabio Guarracino, Laura Carrozzi, Alessandro Celi, Massimo Santini, Fabio Monzani, Salvatore De Marco, Mauro Pistello, Romano Danesi, Lorenzo Ghiadoni, Alessio Farcomeni, Francesco Menichetti, Agostini O Degl’innocenti Sabrina, Antognoli Rachele, Baldassarri Rubia, Bertini Pietro, Biancalana Martina, Borselli Matteo, Brizzi Giulia, Calsolario Valeria, Carpene Nicoletta, Cinotti Francesco, Cipriano Alessandro, Della Rocca Alessandra, Desideri Massimiliano, Forotti Giovanna, Gherardi Marco, Maggi Fabrizio, Mengozzi Alessandro, Malacarne Paolo, Masi Stefano, Monfroni Marco, Morea Alessandra, Nencini Elia, Park Naria, Paterni Simone, Piagnani Chiara, Ruberti Francesca, Sciuto Maria, Serradori Massimiliano, Spinelli Stefano
Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563
Background. This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Methods. This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable. Results. Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6; P < .001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95; P = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions. This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. APPENDIX PISA COVID-19 Study Group Agostini o Degl'Innocenti Sabrina 1 , Antognoli Rachele 2 , Baldassarri Rubia 3 , Bertini Pietro 3 , Biancalana Martina 1 , Borselli Matteo 1 , Brizzi Giulia
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Late treatment
is less effective
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