By analysing a large, diverse population, researchers at the University of San Diego School of Medicine showed that patients using statins before hospitalisation had a substantially lower risk of severe disease and death from COVID-19.
Statins and COVID-19
As global incident cases, hospitalisations and mortality from COVID-19 continue to soar, the need for treatments that reduce disease severity is critical. Early in the pandemic, scientists speculated that common medications targeting ACE2, the SARS-CoV-2 receptor, may influence COVID-19 risk and severity.
These ACE2 targeted medications include statins, which are used to reduce blood cholesterol levels. Statins are widely prescribed for individuals suffering from cardiovascular disease (CVD) and hypertension. Given their known anti-inflammatory and ACE2 binding capabilities, statins were thought to reduce the severity of COVID-19 infection.
As the pandemic progressed, multiple studies have consistently shown that statin use indeed reduces disease severity and mortality from COVID-19. These studies were all small or regional, thus failing to capture demographic diversity. Furthermore, healthy individuals may also use statins to prevent CVD. However, limited study population sizes have not enabled researchers to determine whether any protective effects of statins on COVID-19 are influenced by underlying health conditions.
Large and diverse study population
A study, recently published in PLOS ONE, expanded upon previous research using anonymised data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry. The registry contains health data from diverse patient populations treated for COVID-19 at over 140 hospitals across the US. With over 200 data elements, detailed information provided by the dataset facilitated adjustments for potential confounders later in the analysis. The researchers collated medical records for adult patients hospitalised for COVID-19 from January to September 2020.
Overall, the researchers analysed 10,541 demographically diverse patients. The large study population allowed researchers to address confounding relationships between statin and anti-hypertension medication (anti-HTN) use, as well as underlying CVD and hypertension.
In total, 71% of the patients had CVD, hypertension or both conditions, 85% of which were taking statins and/or another anti-HTN. Additionally, 19% of those in the analysed patient population who did not have CVD or hypertension were on either medication. Overall, 7% of patients were using statins before hospital admission, and 35% were using statins in combination with anti-HTN.
Statistical analyses
The researchers fitted a logistic regression curve to calculate the odds ratio of developing severe COVID-19 with statin and/or anti-HTN use. To improve comparability, they matched patients on medication with those not on medication using propensity score matching techniques. These methods are used to create an artificial control group by matching a treated sample to an untreated sample with similar characteristics. In this study, matching variables included age, sex, ethnicity, hospital site, admission date, socioeconomic status and existing comorbidities. As CVD and hypertension are strongly associated with COVID-19 severity, this was done separately for patients stratified by comorbidity status.
The researchers also investigated patients to assess whether statin and/or anti-HTN use is associated with death or severe outcomes from COVID-19 in the overall study population with multivariable mixed-effects logistic regression curves. The model was adjusted for patient characteristics, pre-existing comorbidities and hospital characteristics.
Associations between using statins and COVID-19 outcomes
Overall, patients on statins, whether used alone or together with anti-HTN, had more than a 40% lower chance of death. Additionally, it was identified that the chances of developing severe COVID-19 are more than 25% lower.
In patients with CVD and/or hypertension, use of statin and/or anti-HTN was significantly associated with 32% lower odds of death. The odds of severe COVID-19 were 20% lower. In contrast, there was no significant reduction in the odds of death and severe COVID-19 in patients who did not have either condition.
These results validated previous findings that statin administration is associated with a lowered risk of death among hospitalised COVID-19 patients. Therefore, statins and anti-HTNs may stabilise underlying diseases to mitigate COVID-19 severity.
From the observed associations alone, the researchers cannot definitively conclude that statin use causes a reduction in COVID-19 severity. Although they have accounted for potential confounders in their study design, some residual confounders may have been overlooked.
Summary
Overall, this study demonstrated the value of using comprehensive datasets and large study cohorts in evaluating the effects of medication. It allowed for matched comparisons between patients and for multiple confounding variables to be controlled. Ultimately, this study verified prior findings that using statins before hospitalisation substantially reduces risk of severe disease and death from COVID-19. The benefits were especially pronounced in individuals with CVD or hypertension, conditions for which statins are prescribed.
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