A recent study suggests that patients taking statin medications have a significantly lower risk for in-hospital death from COVID-19. The findings, published in PLOS ONE, demonstrated that the use of statins prior to admission was associated with a 41% reduction of in-hospital death and a greater than 25% reduction in risk of developing a severe outcome, after adjusting for age, sex, other medical conditions, insurance status, and hospital site.1

“We also found, in a propensity-matched analysis, that most of this benefit was seen in patients with a history of prior heart disease or high blood pressure. For patients without those underlying conditions, there was the suggestion of benefit (16% lower odds of death). However, the results were not statistically significant,” said the lead study author Lori Daniels, MD, professor and director of the cardiovascular intensive care unit at University of California San Diego Health, San Diego, California.1

At the beginning of the pandemic, a great deal of speculation surrounded medications that affect the angiotensin-converting enzyme 2 (ACE2) receptor, including statins, and whether they could influence COVID-19 risk. Researchers theorized that statins inhibited SARS-CoV-2 infection through anti-inflammatory effects and binding capabilities.


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Data on Statins and COVID-19 From the American Heart Association (AHA)’s COVID-19 Registry

Using data from the AHA’s COVID-19 Cardiovascular Disease Registry, researchers analyzed the medical records of 10,541 patients admitted for COVID-19 at 104 hospitals between January and September 2020.

Mean age of the patients was 66 years, and 55% were men. More than half of patients were on Medicare; 36% were non-Hispanic and White, 26% were Hispanic, 26% were Black (26%), and 12% were other or mixed race. Cardiovascular disease (CVD) occurred commonly among these patients; 71% had CVD or hypertension or both. The majority of these patients (85%) were receiving treatment with a statin and/or an antihypertensive agent. In this cohort, 4449 patients (42%) received statins (7% on statins alone and 35% on statins plus antihypertensive agents), and 21% died or were discharged to hospice care.1

Statistical matching was used to compare outcomes for patients who received treatment with statins or an antihypertensive medication vs patients who did not. Researchers matched each patient with 1 or more control participants, using hospital site, month of admission, age, race, ethnicity, sex, and pre-existing conditions.1

Study findings revealed that outpatient use of statins (alone or with antihypertensive agents) was associated with a reduced risk for death (adjusted odds ratio [aOR,] 0.59; 95% CI, 0.50-0.69), after adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications. The use of statins and/or antihypertensive agents was associated with a reduced risk for death among patients with a history of CVD and/or hypertension (aOR, 0.68; 95% CI, 0.58-0.81) in propensity-matched analyses.1

Findings From Previous Literature

Daniels and colleagues conducted a previous study in 2020 that included 170 anonymized medical records from patients receiving care at UC San Diego Health.2 The study showed that the use of statins prior to admission was associated with more than 50% reduction in risk of developing severe COVID-19, after controlling for associated comorbid conditions and for concomitant use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).2 The AHA’s COVID-19 CVD Registry contains de-identified health data for patients treated for COVID-19, and as of July 2021, the researchers had data from more than 49,000 patient records.

“To our knowledge, this is the first analysis to investigate the effect of statins on COVID-19 outcomes in a ‘healthy’ population without underlying CVD or hypertension,” the authors of the study wrote.2

Because the study is observational, it does not prove statins reduce mortality from COVID. “However, the associations we are seeing are very convincing. Given the size of the study, we were able to adjust for a large number of potential confounding factors, and the association between statin use and improved outcomes was strong,” Dr Daniels noted.

Benefits of Statins in COVID-19

Statins have been found to be inexpensive and safe. Dr Daniels noted that patients who have been prescribed statins for their underlying CVD now have yet another reason to take their medications. “The most important take-home message is that we should be proactive about prescribing and discussing the use of statins for our patients with an indication for these medications,” Dr Daniels said. “For patients who may be hesitant to take statins, the fact that they are associated with reduced mortality from COVID-19 may help sway them to take these life-saving medications.”

In Denmark, researchers looked at the association between recent statin exposure and risk for severe COVID-19 infection and all-cause mortality in patients diagnosed with COVID-19 between February 22 and May 17, 2020. The study, which included 4842 patients with COVID-19, showed that statin use was not associated with an increased or decreased risk for all-cause mortality or severe infection.3

Cardiologist Brian Annex, MD, chair of the department of medicine at the Medical College of Georgia at Augusta University, said that statins have been shown to benefit cells that line blood vessels and injury to these endothelial cells has been implicated in many of the complications from COVID-19. “But more work is needed to address this question,” Dr Annex said. “This study would not in itself alter practice patterns for the administration of statins.”

Patients receiving statins may have more stable, well-controlled disease and may be less likely to experience acute events such as plaque rupture, according to cardiologist Gilbert Perry, MD, a professor of medicine at the University of Alabama Birmingham (UAB), Birmingham, Alabama. These patients may also have a greater ability to withstand a severe illness. “Statins in particular are anti-inflammatory, and in this population that may be beneficial,” Dr Perry said. “A potential confounding factor is that patients who know they have CVD or hypertension and don’t take medications may have other poor health behaviors that could contribute to a bad outcome,” said Dr Perry.

Statins More Beneficial to Patients With CVD?

Results of a study showed that the subgroup of patients without documented CVD or hypertension did not show significant benefits from receiving treatment with outpatient statins.1

Wesley Milks, MD, a cardiologist and assistant professor of clinical medicine at The Ohio State University Wexner Medical Center, Columbus, Ohio, said these findings are intriguing because of the wide use of statin medications as well as the recent upward trend in COVID-19 due to the Delta variant. “This cannot directly prove that statin use is associated with improved outcomes in COVID-19. A randomized controlled trial would most definitively answer that question. However, by using observational data, the investigators did seem to design their propensity-matching approach thoughtfully,” said Dr Milks

Despite not showing causality, these findings may provide an additional “nudge” to encourage patients who have indications for statins such as a history of cardiovascular disease, diabetes, very high (low-density lipoprotein [LDL]>190 mg/dL) cholesterol, or (based on their risk factors) an estimated 10-year risk of cardiovascular disease (heart attack or ischemic stroke) exceeding 7.5% to initiate a statin, if recommended by their health care provider,” said Dr Milks.

References

1. Daniels LB, Ren J, Kumar K, et al. Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: findings from the American Heart Association’s COVID-19 Cardiovascular Disease Registry. PLoS ONE. 2021;16(7):e0254635. doi:10.1371/journal.pone.0254635

2. Daniels LB, Sitapati AM, Zhang J, et al. Relation of statin use prior to admission to severity and recovery among COVID-19 inpatients. Am J Cardiol. 2020;136:149-155. doi:10.1016/j.amjcard.2020.09.012

3. Butt JH, Gerds TA, Schou M, et al. Association between statin use and outcomes in patients with coronavirus disease 2019 (COVID-19): a nationwide cohort study. BMJ Open. 2020;10(12):e044421. doi:10.1136/bmjopen-2020-044421