2007May221 Journal Club for Analysis of Complex Datasets Frost FJ, Petersen H, Tollestrup K, Skipper B. Influenza and COPD mortality protection as pleiotropic, dose- dependent effects of statins. Chest 2007; 131:

2007May222 Acknowledgement Carlos Grijalva, MD, MPH Department of Preventive Medicine

2007May223 Background Data on antiinflammatory & immunomodulatory effects of statins suggest they may reduce mortality risks from influenza & COPD. 2 observational studies suggest statins may protect community-acquired pneumonia & COPD. –Mortenson EM, et al. Respir Res 2005; 6: 82. –Mancini GB, et al. J Am Coll Cardiol 2006; 47: 2554.

2007May224 Purpose Objective: compare influenza & COPD mortality risks for low-dose & moderate-dose statins users & nonusers. Design: matched cohort study & 2 case- control studies. Data: Lovelace Patient Database. –Deidentified, longitudinal db of health-care encounter data comprising several HMO’s. Time period: 92Jan01 – 03Dec31.

2007May225 Matched cohort E+: 90+ cumulative days statin exposure prior to death or disenrollment (N=19,058). –Further classified as low daily dose (<4 mg/d) or moderate dose (4+ mg/d). –Mean mg/d for 3-month – 1-yr period after statin initiation. E-: 3 HMO members w/o hx of statin therapy matched to each E+ based on gender, birth yr, & HMO enrollment period (N=57,174). –Enrollment period matching permitted observation of events for both groups during closely comparable time periods.

2007May226 Outcomes Pneumonia or influenza death. Unspecified pneumonia & influenza deaths. COPD deaths.

2007May227 Analysis Logistic & proportional hazards reg. Adjusted for: –Duration of enrollment before initiation of statin therapy (phase 1). –Phase 1 Charlson comorbidity index. –# of different med’s taken during phase 1. –Receiving 3+ influenza vaccinations after statin therapy initiation (phase 2).

2007May228 Case-control studies E+ had more CV comorbidities than E-. –Adjustment for these could have inadvertently affected other outcomes. Pneumonia/influenza study: –D+: Hospital discharge of deceased & pneumonia or influenza. –D-: Surviving patients w/ 1+ in/outpatient visits for pneumonia or influenza. COPD study: –D+: Hospital discharge of deceased & COPD. –D-: Surviving COPD patients w/ 2+ in/outpatient visits.

2007May229 Analysis Logistic reg. Adjusted for: –Sex. –Birth year. –Duration of phase 2 enrollment.

2007May2210 Results: matched cohort logistic regression

2007May2211 Results: matched cohort proportional hazards

2007May2212 Results: case-control study

2007May2213 Concerns Observational study. –Adjusted for few covariates. –Unmeasured confounders? –Confounding by indication. “…unlikely explanation since it would affect both low- and moderate-dose statin users.” –Large cohort (N>75,000). –Propensity scores? –Sensitivity analysis?

2007May2214 Concerns (2) Motivation for case-control studies unclear. –Results similar to cohort study is not a validation of results. “Since the reductions were observed in both the cohort and case-control studies, it is unlikely they could be due to artifacts of either study design or the analysis.” –Cases & controls sampled from same db as matched cohort. Case-control studies had 2x’s events as matched cohort.

2007May2215 Concerns (3) Logistic reg analysis of survival data. –Ignores censoring. –Cannot account for time-dependent covariates. Immortal-time bias: Ayumi!

2007May2216