Study Adds Fuel to the Debate on Statins and Respiratory Illness

Older adults starting on statins had a lower hospitalization risk for pneumonia and other respiratory infections, yet more frequently showed up with respiratory illness in the primary care setting, findings from a U.K. population-based cohort study indicated.

The analysis included adults 65 and up who didn’t get a flu shot. For its primary outcome, propensity score-matching found that statin use was not significantly linked with a lower influenza hospitalization risk, but statin initiators did have a lower risk of being hospitalized with pneumonia (HR 0.86, 95% CI 0.78-0.94) or acute respiratory infections (HR 0.83, 95% CI 0.76-0.89).

Those potential benefits weren’t observed in the primary care setting, however, where modestly increased risks associated with statin use were recorded for influenza-like illness (HR 1.54, 95% CI 1.13-2.09) and acute respiratory infection (HR 1.26, 95% CI 1.16-1.36), though not for pneumonia, Adam Streeter, PhD, of the University of Exeter Medical School in England, and colleagues reported.

“Taken together, these findings suggest that statins may not reduce the occurrence of respiratory infections uniformly across healthcare settings, but may be associated with a lower risk of progression to respiratory infections requiring hospitalization,” the researchers wrote in Open Forum Infectious Diseases. “However, alternative explanations, including residual confounding and differences in health-seeking behaviour and healthcare utilization, cannot be excluded.”

Statins are established medications for cholesterol lowering and general cardiovascular risk reduction. Their benefits may also extend to other settings — from preventing surgery related to inflammatory bowel disease to reducing complications after retinal-detachment surgery — yet the evidence remains mixed regarding the harms or benefits of statin use with acute respiratory infections.

The question of whether statins protect against respiratory illnesses in different settings may be a matter of disease severity, the investigators noted.

“If statins primarily modulate the inflammatory response rather than preventing infection acquisition, they could plausibly reduce progression to severe disease while having little effect on the incidence or clinical detection of milder respiratory infections,” Streeter and colleagues explained.

The present analysis covered one of a pair of studies within the STOPFlu project examining statins’ effects on flu vaccine effectiveness. Included were nine annual patient cohorts from 2010 to 2018 extracted from the U.K. Clinical Practice Research Datalink.

The investigators included people ages 65 years or older registered in primary care who had no record of flu vaccination in the previous 2 years. Controls were matched to statin users in a 5:1 ratio.

Participants were in their mid-70s on average, a majority were women, and over three-fourths were white. Comorbidities such as hypertension, chronic respiratory diseases, and diabetes were similar between statin users and nonusers.

Among the 177,810 controls, there were 7,157 acute respiratory infection hospitalizations, 5,228 pneumonia hospitalizations, and 168 flu hospitalizations. These numbers among the 35,562 statin users were 1,900 acute respiratory infection hospitalizations, 1,451 pneumonia hospitalizations, and 29 flu hospitalizations, respectively.

A major caveat of the study is its inclusion of individuals who weren’t vaccinated against flu, which limits generalizability, but the researchers said this was done in order to exclude the modification of vaccination on influenza risk.