Community-Acquired Pneumonia: Statin Potency and Hospitalization Risk

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Study finds an increase hospitalization risk for community-acquired pneumonia with higher-potency vs lower-potency statins.
Study finds an increase hospitalization risk for community-acquired pneumonia with higher-potency vs lower-potency statins.

Compared with lower-potency statins, higher-potency statins increase rather than lower the risk of hospitalization for community-acquired pneumonia (HCAP), according to a study published in Pharmacoepidemiology.1

This retrospective, population-based analysis used data on 11.3 million patients from a clinical database of medical records (the United Kingdom's Clinical Practice Research Datalink [CPRD] and Hospital Episode Statistics [HES]) to identify all new users of statins (excluding cerivastatin) aged ≥40 years between April 1998 and October 2011. A new user was defined as not having received a prescription for a statin or other lipid-lowering medication within the previous year. Patients were excluded if they had been hospitalized with CAP within 1 year prior to or on the day of study entry to ensure pneumonia had not developed prior to statin use and if they were hospitalized for >1 day within 30 days of study entry to ensure pneumonia was not hospital acquired.  Statins were categorized as higher potency (ie, rosuvastatin ≥10 mg, atorvastatin ≥20 mg, and simvastatin ≥40 mg) or lower potency (ie, rosuvastatin <10 mg, atorvastatin <20 mg, simvastatin <40 mg, fluvastatin, and pravastatin) based on the ability to produce a 45% reduction in low-density lipoprotein (LDL) cholesterol as used in previous studies.2,3 A secondary analysis was conducted on fatal HCAPs.

Of the 348,428 patients included in this study, 217,721 received lower-potency and 130,707 received higher-potency statins. Of the 2251 HCAP cases identified and analyzed with 22,178 matched controls, the rate of HCAP was higher in patients on higher-potency vs lower-potency statins (adjusted hazard ratio [HR] 1.14; 95% CI, 1.03-1.27). The same was true in fatal HCAP cases (adjusted HR 1.29; 95% CI, 1.04-1.59). 

These findings were surprising in light of previous studies associating beneficial respiratory effects with higher-potency vs lower-potency statins. Additionally, these findings run contrary to a shift in treatment guidelines toward an increased use of higher-potency vs lower-potency statins as a more aggressive approach to lipid lowering. Recent guideline changes target a 30% to 50% reduction in LDL cholesterol in lower-risk patients and a 50% reduction in higher-risk patients compared with previous recommendations targeting specific LDL cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels.4,5 

“Several previous studies have suggested that statins may reduce the risk of pneumonia,” said study researcher Kristian Filion, PhD, assistant professor, departments of medicine and of epidemiology, biostatistics, and occupational health at McGill University in Montreal, Canada. “However, statin users tend to be very different from non-users. The hypothesis was that if it were truly a statin effect, stronger statins should reduce the risk of pneumonia more than weaker statins. However, we found that higher-potency statins were not associated with a decreased risk of hospitalization for pneumonia.”

Differences in baseline characteristics were noted between the HCAP cases and matched controls. HCAP was associated with a higher prevalence of asthma, chronic obstructive pulmonary disease (COPD), pneumonia, and cardiovascular-related comorbidities, and of medication use, including use of respiratory drugs, immunosuppressive agents, systemic antibiotics, and systemic corticosteroids, as well as a greater likelihood to have smoked. Differences also emerged between users of the lower-potency vs the higher-potency statins. Current users of a higher-potency statin were more likely to have asthma, COPD, pneumonia, and cardiovascular-related comorbidities vs lower-potency statin users who had a higher prevalence of diabetes mellitus. (Use of pneumococcal vaccine was similar between HCAP cases and controls/high-potency and low-potency statin users.)

This study was limited by the potential for residual confounding factors and the use of CPRD data that were based only on prescriptions and not drug dispensations. Also, mild cases of CAP that did not require hospitalization were not included.

References

  1. Shin JY, Eberg M, Ernst P, Filion KB. Statin potency and the risk of hospitalization for community-acquired pneumonia [published online December 9, 2016]. Br J Clin Pharmacol. doi: 10.1111/bcp.13208
  2. Dormuth CR, Filion KB, Paterson JM, et al; Canadian Network for Observational Drug Effect Studies Investigators. Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases. BMJ. 2014;348:g3244. doi: 10.1136/bmj.g3244
  3. Dormuth CR, Hemmelgarn BR, Paterson JM, et al; Canadian Network for Observational Drug Effect Studies. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ. 2013;346:f880. doi: 10.1136/bmj.f880
  4. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-2934. doi: 10.1016/j.jacc.2013.11.002
  5. Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769-1818. doi: 10.1093/eurheartj/ehr158
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