Glynn R J, Knight E L, Levin R, Avorn J
Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Epidemiology. 2001 Nov;12(6):682-9. doi: 10.1097/00001648-200111000-00017.
Medication use patterns provide popular surrogate measures of disease, yet selective under-use of drugs by elderly patients with potentially unmeasured comorbidity may lead to artifactual "protective" associations between use of specific drugs and mortality. We examined the relation between use of 20 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 years 1991-1994 and filled prescriptions through either Medicaid or that state'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 hospitalization; 41,930 subjects died in the hospital or during the year after discharge. Users of drugs from each of seven therapeutic classes had reduced age- and sex-adjusted rates of death relative to non-users: lipid-lowering agents, nonsteroidal anti-inflammatory agents, beta blockers, thiazides, glaucoma drugs, calcium channel blockers, and anti-anxiety drugs. Adjustment for comorbidity and polypharmacy had little effect on these results. We found similar results in a separate nonhospitalized cohort of 132,071 elderly persons. Much of this observed association appears to be nonetiologic. These findings raise concerns about using observational studies in high-risk populations to infer associations between drug use and outcomes.
药物使用模式是疾病常见的替代指标，然而，患有潜在未测量合并症的老年患者对药物的选择性使用不足，可能会导致特定药物使用与死亡率之间出现人为的“保护”关联。我们研究了新泽西州129,111名65至99岁居民中20类常见药物的使用与死亡率之间的关系，这些居民在1991年至1994年期间至少有一次住院经历，并通过医疗补助计划或该州的老年人及残疾人药房援助计划开具了处方。在住院前的120天内，每种研究药物类别都有超过5000名受试者使用；41930名受试者在医院死亡或出院后一年内死亡。相对于未使用者，来自七个治疗类别的药物使用者经年龄和性别调整后的死亡率有所降低：降脂药、非甾体抗炎药、β受体阻滞剂、噻嗪类利尿剂、青光眼药物、钙通道阻滞剂和抗焦虑药。对合并症和多药治疗进行调整对这些结果影响不大。我们在一个由132071名老年人组成的非住院独立队列中也发现了类似结果。这种观察到的关联大多似乎并非因果关系。这些发现引发了人们对在高危人群中使用观察性研究来推断药物使用与结局之间关联的担忧。
