Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients

Abstract

Aim Assessing the effect of statin therapy at hospital admission for COVID-19 on in-hospital mortality. Methods and Results Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients (1234 men, 923 women; age: 67 y/o (IQR 54-78)) admitted to the hospital were retrieved from the clinical records in anonymized manner. 353 deaths occurred. 581 patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on statin therapy than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: p = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared to the GM non-statin group (17.4%; p = 0.045). The Cox model applied to the CSH function (HR = 0.58(CI: 0.39-0.89); p = 0.01) and the competing risks FG model (HR = 0.60(CI: 0.39-0.92); p = 0.02) suggest that statins are associated with reduced COVID-19-related mortality. Conclusions A lower SARS-CoV-2 infection-related mortality was observed in patients treated with statin therapy prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning

“…The putative benefit of statins in the context of COVID-19 is inconsistent across multiple studies and requires verification in prospective RCTs. Conversely, the preponderance of evidence suggests that statins are not likely harmful and do not need to be discontinued in the hospital ( Masana et al., 2020 ). Many of the reports do not describe the presence or absence of atherosclerotic vascular disease in statin users with COVID-19.…”

Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies

“…Initially, 24 eligible observational studies were identified that reported valuable data on in-hospital mortality and/or COVID-19 disease severity, including three studies of patients with diabetes [14] , [15] , [17] . Of these selected studies, 14 provided data on in-hospital mortality [15] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ( Table 1 )—although one reported only adjusted hazard ratios (HRs) with no crude numbers of deaths in statin users vs non-users and, therefore, could not be included in the meta-analysis (authors were contacted, but did not communicate their results) [26] —while 11 studies reported data on COVID-19 severity (as determined by ICU, IMV; Table 2 ) [18] , [22] , [23] , [27] , [28] , [30] , [31] , [32] , [33] , [34] , [35] . Also, a study by Tan et al [36] collected very few events in a Chinese population (personal communication from the authors), thereby preventing the use of this study in the final analysis.…”

“…The included observational studies reporting data on in-hospital mortality are listed in Table 1 [15] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] . Results of the corresponding meta-analysis are illustrated in Fig.…”

“…The list of included observational studies reporting data on disease severity (ICU, IMV) is presented in Table 2 [18] , [22] , [23] , [27] , [28] , [30] , [31] , [32] , [33] , [34] , [35] , while results of the corresponding meta-analysis are illustrated in Fig. 3 .…”

“…As statin users have different clinical characteristics from non-users, which might expose them to a greater risk of developing more severe COVID-19 infection, it is important to take into account the potentially confounding factors that could influence the final results. In 10 series of data—six considering in-hospital mortality ( Table 1 ) and four considering COVID-19 severity ( Table 2 ) [19] , [21] , [23] , [24] , [27] , [28] , [31] , [33] —multivariable analyses or those adjusted for covariates, if available, resulted in more favourable results than univariate analyses in patients treated with statins compared with patients not treated with statins at admission to hospital: adjusted OR (mean ± SD) 0.73 ± 0.31 vs non-adjusted OR 1.44 ± 0.84; P = 0.0028; Fig. 4 ).…”