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Statin Use and Severe Disease Outcomes in COVID-19
Quick Takes
- Statin therapy appears safe to use during the global COVID-19 pandemic.
- A Detroit Medical Center study found that after adjustments for age, sex, and medical comorbidities, antecedent statin use significantly reduced mortality among patients hospitalized with confirmed COVID-19.
- Moderate-dose or high-dose statin use was associated with reduced mortality from COVID-19 in a propensity score-matched cohort, but low-dose statin use was not.
Study Questions:
Does home statin use impact outcomes from severe coronavirus disease 2019 (COVID-19)?
Methods:
This retrospective cohort study included 1,014 patients ≥18 years of age who presented to Detroit Medical Center with a confirmed COVID-19 diagnosis (nasopharyngeal or oropharyngeal polymerase chain reaction swab) between March 10 and June 30, 2020. The study excluded pregnant women, persons readmitted during that time frame, patients transferred to another hospital for extracorporeal membrane oxygenation, and those under the age of 18. Home medications and comorbidities were recorded upon initial contact, specifically noting home use of statins. Primary study outcome was mortality. Secondary outcomes were need for mechanical ventilation and intensive care unit (ICU) admission. Using multiple logistic regression, a propensity-matched cohort consisting of 233 pairs of matched patients (466 persons) was identified.
Results:
In the overall, unmatched cohort of 1,014 patients, median age was 65 (interquartile range 53-73), 530 (52.3%) were males, 753 (74.3%) were African Americans, median body mass index (BMI) was 29.4 (interquartile range 25.1-35.9), and 615 (60.7%) had Medicare insurance. In that cohort, 454 (44.8%) were antecedent statin users. Mortality for the total cohort was 29.3% (30.4% statin users vs. 28.4% statin non-users; p = 0.49). Mechanical ventilation was required by 24.7% (26.4% statin users vs. 23.2% statin non-users; p = 0.23), and ICU admission was required by 33.2% (35.9% statin users vs. 31.1% statin non-users; p = 0.11). Baseline characteristics of the 2 groups differed significantly with regard to age, hyperlipidemia, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, end-stage renal disease on dialysis, history of stroke, congestive heart failure, and preexisting lung diseases. After adjusting for age, sex, race, BMI, insurance, smoking status, and 11 comorbidities, multivariable regression analysis showed that antecedent statin use was associated with a significant decrease in mortality (odds ratio [OR] 0.66; 95% confidence interval [CI], 0.46-0.95; p = 0.03), but not with mechanical ventilation or ICU admission. And in an optimal model that included only covariates that contributed significantly to the model (age, sex, diabetes mellitus, preexisting lung disease, hypertension, and statin use), statin users had a significant reduction in all-cause mortality (OR 0.64; 95% CI, 0.47-0.87; p = 0.005). In the propensity score-matched cohort, baseline characteristics of 233 statin users and 233 statin non-users were similar with regard to age, sex, race, BMI, insurance status, smoking, and 11 other comorbidities. In the propensity score-matched cohort, statin use was associated with reduced mortality (OR 0.56; 95% CI, 0.37-0.83; p = 0.004) but was not associated with mechanical ventilation or ICU admission. A clear dose-response relationship was observed between statin dose and mortality. Compared to statin non-users, moderate-dose statin use was significantly associated with reduced mortality (OR 0.52; 95% CI, 0.31-0.87; p = 0.01), as was high-dose statin use (OR 0.54; 95% CI, 0.29-0.99; p = 0.047). However, low-dose statin use was not associated with reduced mortality.
Conclusions:
This retrospective study found that after adjusting for demographic factors and comorbidities, mortality with COVID-19 was significantly reduced among statin users in comparison with statin non-users in the overall cohort and in a propensity score-matched cohort. The finding suggests that statin therapy appears safe during the global pandemic. The authors state that randomized controlled trials assessing the possible benefit of statin use in COVID-19 should be considered.
Perspective:
Several observational studies and meta-analyses have found that statins significantly reduced the risk of severe or fatal outcomes in COVID-19, whereas others did not confirm such an association. This study found that the beneficial effect of statins in COVID-19 was observed only after adjusting for demographic variables and comorbidities. In a propensity score-matched cohort, the effect was dose dependent. Worldwide, there are several ongoing randomized controlled trials of statins, alone or in combination with other drugs, in the treatment of COVID-19. Two such trials are ongoing in the United States: the STATCO19 (Atorvastatin as Adjunctive Therapy in COVID-19) trial and COLSTAT (Colchicine/Statins for the Prevention of COVID-19 Complications Trial). The STATCO19 trial will randomize 300 patients admitted with suspected COVID-19 who are not on chronic statin therapy to atorvastatin 40 mg plus standard of care versus standard of care alone. Primary outcome is the proportion of patients who progress to severe or critical disease requiring ICU admission and/or emergency salvage therapy or death. COLSTAT will randomize 466 patients admitted to a non-ICU floor with confirmed COVID-19 infection to rosuvastatin 40 mg daily plus colchicine and standard of care versus standard of care alone. Primary outcome is severity of COVID-19 infection over a period of 30 days as defined by the World Health Organization Ordinal Scale.
Clinical Topics: COVID-19 Hub, Dyslipidemia, Nonstatins, Novel Agents, Statins
Keywords: Hydroxymethylglutaryl-CoA Reductase Inhibitors, COVID-19, Pandemics, Intensive Care Units, Hospitals, Polymerase Chain Reaction, Respiration, Artificial, Extracorporeal Membrane Oxygenation
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