Pneumonia mortality rates lower for statin users

In a large, population-based cohort study published in the Archives of Internal Medicine, current use of statins by patients hospitalized with pneumonia was associated with a decreased risk of death after hospital admission compared with nonusers of statins.

The study followed 29,900 Danish patients (median age, 73 y) hospitalized between January 1, 1997, and December 31, 2004, with first-time pneumonia diagnoses. Hospital and prescription databases and the Danish Civil Registration system provided information on the primary end point of mortality within 30 and 90 days after the hospital admission date and on the secondary end points of bacteremia and pulmonary complications for statin users and nonusers. Current statin use was defined as at least 1 filled prescription for a statin within 125 days before the hospitalization.

The same sources provided data on numerous covariates, including comorbidities, socioeconomic factors, laboratory findings, and use of disulfiram, immunosuppressants, and antibiotics, as well as agents with the potential to confound the effects of statins: beta-blockers, low-dose aspirin, and angiotensin-converting enzyme (ACE) inhibitors. Cox regression analysis was used to calculate mortality-rate ratios (MRRs) for the primary end point.

A total of 1,372 (4.6%) of the 29,900 patients were classified as current statin users. Of these, 61% had been prescribed simvastatin, 15% pravastatin, 15% atorvastatin, and 9% other statins or a combination of statins.

After controlling for a wide range of variables, final adjusted MRRs for statin users overall were 0.69 for 30-day mortality (95% CI, 0.58–0.82) and 0.75 for 90-day mortality (95% CI, 0.65–0.86), or 10.3% for statin users versus 15.7% for nonusers after 30 days and 16.8% versus 22.4% after 90 days. Simvastatin users demonstrated the lowest 30-day adjusted MRR (0.60; 95% CI, 0.48–0.75). Adjusted MRRs were higher in users of atorvastatin (MRR=0.81; 95% CI, 0.53–1.23) and users of pravastatin (MRR=0.96; 95% CI, 0.66–1.40).

When 1,346 statin users were matched with 1,346 nonusers, the adjusted MRR for statin users was 0.64 for 30-day mortality (95% CI, 0.52–0.80) and 0.71 for 90-day mortality (95% CI, 0.60–0.84). Conversely, patients who had stopped using statins >125 days before hospital admission demonstrated no decrease in mortality risk, and a strong association with adverse outcome was observed in patients who stopped taking statins within 90 days after hospital admission (adjusted 90-day MRR=1.75; 95% CI, 1.51–2.02). No decrease in pneumonia mortality risk was observed in patients using other cardiovascular drugs. The adjusted relative risk for bacteremia among statin users was 1.07 (95% CI, 0.69–1.67); the adjusted relative risk for pulmonary complications was 0.69 (95% CI, 0.42–1.14).

The study concludes that statin use at the time of hospital admission was associated with decreased 90-day mortality, with the greatest benefit appearing to occur early in the infection process. The authors suggested the need for randomized trials to further explore this association, adding, “Given the availability of statins, with their relatively low cost and mild adverse effects, positive results of statin therapy trials in patients with pneumonia would have substantial clinical and public health implications.”

In an accompanying editorial, Kasturi Haldar, PhD, stated that “in addition to their cholesterol-lowering effects and benefit in preventing stroke, coronary heart disease, myocardial infarction, and peripheral artery disease, statins also seem to reduce inflammation in patients with cancer, dementia, severe infection, and pulmonary hypertension,” citing evidence from the Danish study that “C-reactive protein levels were lower in statin users compared with nonusers, which suggests that statins reduce inflammation.” He suggested that “it may be useful to consider clinical research testing of combinations of statins with existing antibiotic agents to evaluate whether it is possible to develop optimized combination therapies effective against both acute and persistent infections.”

SOURCES
Thomsen RW, Riis A, Kornum JB, Christensen S, Johnsen SP, Sørensen HT.
Preadmission use of statins and outcomes after hospitalization with pneumonia: Population-based cohort study of 29,900 patients. Arch Intern Med. 2008;168:2081–2087.

Haldar K. Targeting the host to control an infection disorder [editorial]. Arch Intern Med. 2008;168:2067–2068.