Kivimäki, M

Strandberg, TE

English

UCL Discovery

  Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website.  Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.  Journal Pre-proofIncreased mortality risk associated with statins in the CORONADO studyTimo E. StrandbergPII: S1262-3636(21)00033-1DOI: https://doi.org/10.1016/j.diabet.2021.101250Reference: DIABET 101250To appear in: Diabetes & MetabolismMika KivimäkiPII: S1262-3636(21)00033-1DOI: https://doi.org/10.1016/j.diabet.2021.101250Reference: DIABET 101250To appear in: Diabetes & MetabolismReceived Date: 26 October 2020Please cite this article as: Strandberg TE, Kivimäki M, Increased mortality risk associated withstatins in the CORONADO study, Diabetes and amp; Metabolism (2021),doi: https://doi.org/10.1016/j.diabet.2021.101250This is a PDF file of an article that has undergone enhancements after acceptance, such asthe addition of a cover page and metadata, and formatting for readability, but it is not yet thedefinitive version of record. This version will undergo additional copyediting, typesetting andreview before it is published in its final form, but we are providing this version to give earlyvisibility of the article. Please note that, during the production process, errors may bediscovered which could affect the content, and all legal disclaimers that apply to the journalpertain.© 2020 Published by Elsevier.Diabetes & Metabolism NA--Manuscript Draft-- Manuscript Number: DIABET-D-20-00801R1Article Type: Letter to the Editor/Lettre a la redact.Keywords: statin;  COVID-19;  mortalityCorresponding Author: Timo Strandberg, MD, PhDFINLANDFirst Author: Timo Strandberg, MD, PhDOrder of Authors: Timo Strandberg, MD, PhDMika KivimäkiManuscript Region of Origin: FINLANDAbstract: NAPowered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationJournal Pre-proofDear Editor,  23 February, 2021   Concerning our revision, we do not know what to do. We got reviewer comments, which were not about our letter to the Editor. I have sent emails about this to you, but got no answer. Please advice. Sincerely,  Timo Strandberg, MD Detailed Response to ReviewersJournal Pre-proof1  Increased mortality risk associated with statins in the CORONADO study  Timo E Strandberg1,2, Mika Kivimäki1  1 University of Helsinki and Helsinki University Hospital, Helsinki, Finland 2 University of Oulu, Centre for Life Course Health Research, Oulu, Finland  Correspondence to: Timo Strandberg, MD  Helsinki University Hospital, P.O. Box 340, 00029 Helsinki, Finland  Email: timo.strandberg@oulu.fi  Received 26 October 2021; Accepted 10 March 2021  Conflicts of interests: none   Manuscript 1  2  3  4  5  6  7  8  9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Journal Pre-proof2  The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) study investigators reported an increase in mortality associated with ongoing statin treatment in 2449 inpatients with type 2 diabetes (T2D) during the coronavirus disease 2019 (COVID-19) pandemic [1]. Crude 7-day mortality rates were 12.8% among statin users and 9.8% among non-users (P = 0.02), with the corresponding percentages for 28-day mortality being 23.9% and 18.2%, respectively (P < 0.001). Calculated unadjusted odds ratios (ORs) based on these figures were 1.36 [95% confidence interval (CI): 1.06–1.76] and 1.41 (95% CI: 1.15–1.72).  This difference in mortality was not unexpected as the statin users were older (mean age: 72 and 70 years, respectively), had diabetes of longer duration (15 and 12 years, respectively), and more hypertension (87% and 74%, respectively), heart failure (14% and 10%, respectively) and chronic obstructive pulmonary disease (COPD; 12% and 8%, respectively), as well as more macrovascular (54% and 27%, respectively) and microvascular (50% and 41%, respectively) complications than non-users of statins. After propensity score matching, the reported 7-day and 28-day ORs for mortality risk were 1.74 (95% CI: 1.13–2.65) and 1.46 (95% CI: 1.08–1.95), respectively. Nevertheless, it is rather surprising that the mortality risk prevails, even despite higher point estimates after adjusting for patients who had more factors associated with poor COVID-19 prognosis. Statin treatment has been shown to be beneficial in randomized controlled trials of particular patient groups, such as patients with diabetes, who are most at risk of COVID-19. In addition, the majority of analyses concerning mortality risk during COVID-19 have thus far indicated a beneficial or neutral effect of statin use [2]. Large studies from China [3] and the US [4,5], for example, indicated a 12–46% reduced mortality risk among statin users, including those with diabetes, and a UK-wide analysis of 2.9 million patients with T2D (mean age: 70 years) found that the risk of death due to COVID-19 was 28% lower among statin users [5].   1  2  3  4  5  6  7  8  9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 JouralPre-proof3  Thus, the unexpected statin mortality results so far from CORONADO may represent outlier findings and call for more detailed analyses of underlying factors.     1  2  3  4  5  6  7  8  9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Journal Pre-proof4  References 1. Cariou B, Goronflot T,  Rimbert A, Boullu S,  Le May C, Moulin P, et al. Routine use of statins and increased mortality related to COVID-19 in inpatients with type 2 diabetes: Results from the CORONADO study. Diabetes Metab 2020; S1262-3636(20)30153-1.  doi: 10.1016/j.diabet.2020.10.001.  2. Scheen AJ. Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies. Diabetes Metab 2020;101220. doi: 10.1016/j.diabet.2020.101220. 3. Zhang XJ, Qin JJ, Cheng X, Shen L, Zhao YC, Yuan Y, et al.  In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab 2020; 32: 176-87. 4. Mallow PJ, Belk KW, Topmiller M, Hooker EA. Outcomes of hospitalized COVID-19 patients by risk factors: Results from a United States hospital claims database. J Health Econ Outcomes Res 2020; 7: 165-74. doi: 10.36469/jheor.2020.17331doi: 10.1007/s40265-020-01365-1. 5. Saeed S, Castagna F, Agalliu I. Statin use and in-hospital mortality in diabetics with COVID-19. J Am Heart Assoc 2020 Oct 23;e018475. doi: 10.1161/JAHA.120.018475 6. Holman N, Knighton P, Kar P, O’Keefe J, Curley M, Weaver A. Risk factors for Covid-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol 2020; 8: 823–33.   1  2  3  4  5  6  7  8  9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Journal Pre-proof

Increased mortality risk associated with statins in the CORONADO study

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Increased mortality risk associated with statins in the CORONADO study

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