Paradoxical relations of drug treatment with mortality in older persons

Medication use patterns provide popular surrogate measures of disease, yet selective under-use of drugs by elderly patients with potentially unmeasure d comorbidity may lead to artifactual "protective" associations between use of specific drugs and mortality. We examined the relation between use of 2 0 common classes of drugs and mortality among the 129,111 residents of New Jersey 65-99 years of age who had at least one hospitalization during the y ears 1991-1994 and filled prescriptions through either Medicaid or that sta te's Pharmacy Assistance for the Aged and Disabled program. Each study drug class was used by more than 5,000 subjects during the 120 days before hosp italization; 41,930 subjects died in the hospital or during the year after discharge. Users of drugs from each of seven therapeutic classes had reduce d age- and sex-adjusted rates of death relative to non-users: lipid-lowerin g agents, nonsteroidal anti-inflammatory agents, beta blockers, thiazides, glaucoma drugs, calcium channel blockers, and antianxiety drugs. Adjustment for comorbidity and polypharmacy had tittle effect on these results. We fo und similar results in a separate nonhospitalized cohort of 132,071 elderly persons. Much of this observed association appears to be nonetiologic. The se findings raise concerns about using observational studies in high-risk p opulations to infer associations between drug use and outcomes.